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The asymmetric synthesis of β-lactams
WW 4020876 53 00 + .lM m!y1986 Pcrgamon Journals Ltd
Terrahedron Vol 42. No. IR. pp. 5123 to 5137. I986 Prmtcd I” Great Rnum
The Asymmetrlc Synthesis of B-Lactams. Stereocontrolled Asymmetric Tandem Michael Additions and Subsequent Alkylations of E-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMe]. X-Ray Crystal Structure of (RS)-E-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMel
Stephen C. Davies,* Isabelle M. Dordor-Hedgecock, Kevin H.Sutton and Jonathan C. Walker, The Dyson Perrins Laboratory, South Parks Road, OXFORD, OX1 39Y,
U.K.
and Richard H. Jones and Keith Prout, Chemical Crystallography Laboratory, 9, Parks Road, OXFORD, OX1 3PD, U.K. (Rewiced
m UK 26 June 1986)
Summary: Michael addition of methyllithium to the E-crotonyl complex (RS)-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMe] followed by trapping of the resultant enolate with methyl iodide gives (RS)-C(n'-C,H,)Fe(CO)(PPh,)COCH(Me)CHMe,l (d.e. > 1OO:l). also generated by treatment of (RS)-[(n'-C,H,)Fe(CO)(PPh,)COCH,CH(OMe),l with three equivalents of methyllithium and methyl iodide. Addition of fl-butyllithium to the (RS)-E-crotonyl complex followed by protonation with methanol occurs with high diastereoselectivity. Quenching with methyl iodide gives (RS)-C(n'-C,H,)Fe(CO)(PPh,)COCH(Me)CH(Me)E-Bul, also generated by treating either diastereoisomer of [(n'-C,H,)Fe(CO)(PPh,)COCH,CH(Me)OMel with two equivalents of c-butyllithium and methyl iodide. Decomplexation gives the known erythro-2,3-dimethylheptanolc acid. Similarly, Michael addition of lithium benzylamide and electrophilic quenching with methanol or methyl iodide occurs with high diastereoselectivlty and gives upon decomplexation, q-methyl- and cis-3,4-dimethyl-N-benzyl-B-lactams respectively. The stereochemical results are rationallsed by addition occurring to the E-crotonyl complex in the anti (C-O to CO) and cisoid conformation and subsequent alkylation of the unhindered face of the E-enolate generated. Confirmation is provided by an X-ray crystal structure analysis of When repeated with the optically pure (RS)-E-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMel. (S)-E-crotonyl complex, decomplexation gives essentially optically pure (2R),(3R)-c-)-Nbenzyl-2,3_dimethylheptanamide, (4S)-(-)-4-methyl- and (3R),(4S)-(-)-cis-3,4-dimethyl-Nbenzyl-B-lactams. Introduction: The chiral auxiliary C(n'-C,H,)Fe(CO)(PPh,)lt exerts powerful stereochemical control during the reactions of attached acyl ligands.'*'
For example, the Z-crotonyl iron complex 1 is
deprotonated in the cisoid conformation by n-butyllithium to the dienolate 2 which undergoes highly stereoselective a-methylation from the unhindered face generating 3 as a single diastereoisomer.'*'.
2
We describe here in detail the highly stereoselective tandem Michael additions to and subsequent electrophilic quenching of the racemic E-crotonyl iron complex j! which result in the stereocontrolled synthesis of o- and g-substituted iron acyl complexes.
t
Part of this work has been
Unless otherwise stated all complexes are racemic but only those with the R configuration at iron are drawn for clarity. 5123
S. G. Dnvw, et al.
5124 the subject
of a preliminary
independently
and similar
communication’
by Liebeskind
reactivity
We then go on to report
et.al.”
was subsequently
reported
such tandem reactions
of
and lithium benzylamide to the enantlomerlcally pure (S)-E-crotonyl complex -4 which -n-butyllithium upon decomplexatlon give essentially optically pure o,6-disubatltuted carbonyl compounds and I(-mono- and 3,4-disubstituted The possibility additions
of
6-lactams
carbanlons
to a.B-unsaturated
enolate
thus formed has been recognlsed
part
the a,t3-unsaturated
of
particular, system,
where part
moderate
6-centres.“’ achieved Results
respectively,
all
of the tandem stereocontrolled
carbonyl
or all
of
known absolute of two chlral
In general
some time.
has proved
acyclic
cases i.e.
of
the use of a chiral
moiety
of
the
auxiliary
approach.6*7*’
is contained
in the formation
however,
via Michael
alkylatlon
the more successful
carbonyl
can be achieved
addition,
configuration. centres
compounds and subsequent
the a,E-unsaturated
For the corresponding Michael
for
equivalent
to good stereocontrol
in the initial
carbonyl
of
formation
in a ring
both the o-
good stereocontrol
as In
and
has only
been
at the 6-centre.6*a*9
and Discussion:
Several
methods for
recently.‘*“*” methoxide
the synthesis
The most efficient from the 6-methoxy
complex -5 via aldol a readily
generates
acyl
of the E-crotonyl synthesis
complexes
involves
complex 2 have been described
5 and 1 which are derived
reactions
with acetaldehyde
separable
15:l
mixture
iron
the sodium hydride-promoted
and subsequent
0-methylation.”
the E- and Z-crotonyl
of
elimination
from the parent
of
acetyl
This route
complexes
2 and 1
respectively.
4. NoH /Ma1
NaH \
+
I5 : I
Addition at -78’C
of methyllithlum
generated
300 MHz ‘H n.m.r. established
the a,B-dimethyl
from the chemical a Michael
by the methyl intermediate addition
iodide. enolate
in the clsold
butanoyl
shift
(60.91)
The formation addition Since
by methyl
with
of
the a-methyl
doublet
of 2 as the exclusive
thus generating
This
the iron
i.
(d.e.
to the a-centre
indicates
an enolate
>lOO:l
by
were of the
that 4 is
which is
from the unhindered
is consistent
E-enolate
complex 4 in THF
which is characteristic
product
to generate
must have occurred
iron
dlastereoisomer
of
must have the E-conflguratlon. conformation
to the E-crotonyl
conflguratlons
the methyllithium
a-methylatlon
iodide
complex 2 as a single
The relative
spectroscopy).
RS.SR-diastereoisomer.” undergoing
followed
then trapped
face’,
with 2 undergoing
the a Michael
The asymmetric synthesisof B_lactam8
in Oommonwith
anti to the co
ligand
preference
5 to adopt
the
ror
CO llgand
all
other
then molecular a aisoid
would d88tabili8e
iron
models
These prediction8 bond length8
in Tab18 2.
the corresponding
anti
to the
between
CO llgand
were
VeFifi8d
by an X-ray
around
(Figure
the
2).
are iron
the blockfng
effect
given oentre
The E-crotonyl
the C-O and the C-C bonds being
illustrates
Selected
bond lengths
F8(1
)-PC1
Fe(1
I-Ccl
Fe(1
)-C(5)
cc1 )-Of1 Cfl
f 1 )
for
Huckel
of
the
39’.
ti),
Crystal in Table
StW3.UrS
and
la
or f
(Figure
Coordinate8
claold
with
I). are
oxygen
the torsional
down the Fe-P axis
listed is angle and
llgand.
and torsional
angles
f’)
wfth
e.S.d.8
in
fRS)-E-j:(n’-C,H,)Fe(CO)(PPh,)COCH-CHHcl].
2.195(l)
Fe(l)-C(l)-C(2)
1.958(3)
C(1 )-C(2)-C(3)
121.?(4)
1.738(3)
C(2)-C(3bC(4)
125.8(5)
1.223(4)
Fe(l)-P(l)-C(11)
116.1(1)
1.484(6)
C(l)-Fe(l)-P(l)-C(11)
118.9(3)
I-Cfl
)-O(t)
-161 -30
C(l)-C(2)-C(3)-C(4)
)
171
95.2(2)
C(5)-Fell)-C(l)-C(2)
18
69.2(l)
C(3)-C(2)-Cfl
39
Fe( 1 )-Pt
PC1 f-Fe(t
)-C(5)
91.8(l)
Fe(1
)-O(l)
122.9(3)
I-C(1
a clear
$-hFdrOg8n
l*
C(3)-C(4)
)-P(i
the
and the acyl
3 shows a projection
C(S)-Fe’e(t
f-~8(t
atomic
to octahedral
conformation
1.316(6)
c(i
SrtSlySiS
1 and final
18 close
C(2)-C(3)
)-C(5)
between
1.488(S)
)-C(2)
C( 1 I-Fell
oxygen remain8
indicate
TRANSOID
Figure
f”)
the acyl
oonformation.
trlphenylphosphfne
angles
that
calculations’4
interaUtiOn8
transoid
Table
parentheses
type, ‘*
this
It
and bond angles
The geometry
of
Bt8rlC
coniormation.
clsolo
Selected
acyla
and extended
5125
)-O(l) 1 )-C(
11 f-C<
16)
-66
l The atomic coordinates iOr thi8 work are available on request from the Director of the Cambridge Crystrallographio Data Centre, University Chemloal Laboratory, Lensfield Road, Cambridge, CB2 1EB (Oreat Britain). Any request should be accompanied by the full literature citation for this papar.
5126
S. G. DAVIESet cd.
Figure 1.
Figure 2.
Figure 3.
5127
Table 2. Atomic Coordinates sad Equivalent Isotropic Temperature Factors I~IIIIPII~CI~II~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Atom -W(l) P(l) C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) CflO) Cfll) Cf12) C(13) C(14) Cf15) C(M) Cf17) CflR) Cf19) C(20) Cf21) Cf22) Cf23) Cf24) Cf25) Cf26) Cf27) C(2R) O(1) O(2) A(1) A(2) H(3) A(4) A(5) A(6) H(7) A(8) R(9) AflO) A(111 Hf12) Af13) H(14) II Hfl6) Hf17) A(181 A(191 Bf20) A(211 Iif Rf231 A(241 Rf25)
y/b
_-0.17634(31 0.30198(4) 0.1725(2) O.lOE5f3) 0.1287(3) 0.0741(4) 0.1209(2) 0.1301(2) 0.0743(2) 0.1228(3) 0.2078(31 0.2123(2) 0.3195(2) 0.3802(21 0.3889(31 0.3383(3) 0.2779(3) 0.2676(21 0.3980(21 0.4650(2) 0.5360(2) 0.5405(2) 0.4736(2) 0.4018(2) 0.3231(2) 0.3824(2) 0.3981(2) 0.3556(3) 0.2957(3) 0.2792(2) 0.2214(2) 0.0833(2) 0.0469(j) 0.1994(31 0.0607(41 0.003201 0.0972(4.) 0.1167(2) 0.0118(2) 0.0970(3) 0.2595(3) 0.2592(2) 0.4209(2) 0.4330(3) 0.3348(3) 0.2332(3) 0.2259(2) 0.4602(2) 0.5820(2) 0.5943(21 0.4741(21 0.3523(2) 0.4147(2) 0.4406(21 0.3762(5) 0.2705(3) 0.2395(21
0.14239(2) 0.13633(3) 0.0389(2) 0.0014(2) -0.0574(2) -0.0935(3) 0.1502(2) 0.1357(2) 0.1787(2) 0.2372(2) 0.2299(2) 0.166512) 0.0579(l) 0.0062(2) -0.0519(2) -0.0589(2) -0.OOElf2) 0.0499(2) 0.1379(l) 0.1862(2) 0.1850(Z) 0.1362(2) O.OE87(21 O.OE92f2) 0.2073(l) 0.1985(2) 0.2526t2) 0.3158(2) 0.3252(2) 0.2707(2) 0.0034(l) 0.1601(2) 0.0301(2) -0.0732(2) -0.1344(3) -0.0704(3) -0.oe94f3) 0.0392(2) o.l6e7(2) 0.2779(21 0.2602(21 0.1491(2) O.Q151(2) -O.OS53(2) -0.1046(2) -0.0164(2) O.OE51(2) 0.2229(2) 0.2185(2) 0.1315(2) O.O526(2) 0.0571(2) 0.1570(2) 0.2503(2) 0.3583(2) 0.3680(21 0.2785(2)
SIC
__-
U(iso) or lJ(eqnir) -________-_--__--
0.11773(4) 0.26907(E) 0.1115(4) 0.2063(41 0.2689(5) 0.4046(6) 0.2943(41 -0.1376(41 -0.0533(41 0.0125(4) -0.0304(4) -0.1230(4) 0.4034(3) 0.3794(5) 0.4857(6) 0.6139(5) 0.6399(4) 0.5335(4) 0.1515(3) 0.1844(4) 0.0908(4) -0.0349(4) -0.0704fO 0.02150) 0.4239(3) 0.5638(4) 0.6779(4) 0.6554(5) 0.5184(51 0.4040(4) 0.0348(31 0.4ocot3) 0.2234(4) 0.2775(5) 0.3726(6) 0.3734(61 0.5172t6) -0.1893(4) -0.0455(4) 0.0630(4) -0.00380) -0.1523(41 0.3053(5) 0.4592(6) 0.6617(53 0.7222(4) 0.5424(43 0.2672(4) 0.1159(41 -o.oe34(4) -0.1490(4) -0.0018(4) 0.57ROf4) 0.7657(4) 0.7183(5) 0.4950(5) 0.3145(4)
0.0337 0.0295 0.0419 0.0545 0.0638 o.oe5g 0.0435 0.0519 0.0556 0.0539 0.0542 0.0520 0.0335 0.0526 0.0627 0.0579 0.0502 0.0425 0.0345 0.0431 0.0517 0.0517 0.0497 0.0432 0.0348 0.0433 0.05OE 0.0548 0.0565 0.0470 0.0567 0.0636 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0:045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045
The E-crotonyl iron complex I! reacted with n-butyllithium to generate the enolate E
which on
addition of methyl iodide gave essentially a single dlastereoisomer of the o,g-dimethylheptanoyl oomplex 11; (d-e. >lOO:l:l:l as determined by 300 l4Rz *H n.m.r. spectroscopy).
The relative
configuration ln -11 of the lron-centre to the a-chiral centre was established as RS,SR from the chemical shift (60.98) of the o-methyl doublet" and indicated that as before Michael addition had occurred to 2 In the ciaoid conformation.
The relative configuration of the g-centre was assigned
on the assumption that the i-butyllithium had attacked 2 in the oiaoid conformation. with the COIIfigWatiOm Of fl carbonyl oxygen8 m, from the unhindered iaae. In this way the relatiVe were
astQgned
aa
RSS,SRR and this was confirmed by oxidatlve decomplexatlon to the known,zY!!?!X
5128
S. G. Dams
carboxyllc
acid.*a
dlastereolsomer
et al.
Protonation
of enolate -10 with methanol gave complex -13 as a single as RS,SR by analogy with the formation of RSS,SRR-12. -
assigned
bn no
’ 7))/ 0
The extension precursors studied
of
this
of
this
B-lactams,
’
methodology l
type of reaction.
which on protonation
to the formation
* I ’ has been communicated Thus, addition
gave the g-amlnoacyl
of
complex
Decomplexation
of racemic
by Llebeskind
lithium
g-amino et.al.’
benxylamide
acyl
: Bu
iI
complexes,
We have independently
to 2 generated
enolate
1’(
(RR,SS)-
-15 as a single diastereoisomer. 16.“*” Trapping enolate Ift with methyl -
of -15 gave the known u-methyl-8-lactam gave (RSR,SRS)-17 as a single diastereolsomer. The relative conriguratlons in complexes or -17 were assigned by analogy with complexes -13 and -11. Confirmation was provided by the appearance of the a-methyl doublet for -17 at 61.12 in the ‘H n.m.r. spectrum and by oxldative iodide
-15
decomplexation
of -17 to give the known -cls-3,4-dlmethyl-g-lactam 18.” Epimerlsatlon of -18 by with base gave a 1:2 mixture of -18 and its trans-epimer, Yw thus demonstrating that the
treatment -cls-B-lactam
1s the thermodynamically
less
m
stable
dlastereoisomer. co
m
!? We
shown previously
have
non-nucleophilic E-crotonyl
iron
base,
that
treatment
sodium hydride,
complex i.‘”
the enolate -10. which is then trapped
of the B-methoxy acyl
complexes
in the elimination
of methanol
results
Treatment
of either
generated
Presumably
the first
situ
by Michael
addition
Subsequent
addition
of methyl
iodide
2 or 1 with equivalent
of
gave -11 again
two equivalents
promotes
the second as a single
5 and 1 with the
elimination
equivalent
and generates to generate
of n-butyllithium.
diastereoiscmer.
the
of ;-butyllithium 4 in --
The asymmetric synthesis of /Mactams
5129
I
p-Buli
Similarly, methylllthium
treatment followed
of the 8-dimethoxy
by addition
The formation enolate
acyl
or methyl
of 2 from -19 is consistent 8 which is then qethylated.
complex ‘* -19 with three equivalents of yielded complex 2 as a single diastereoisomer.
iodide
with two sequential
elimination-Michael
Mdi
additions
giving
c
I
Mdi
9
In order efficient
to extend
decomplexation
the highly
diastereoselective
methods described
tandem Michael
to the asymmetric
carbonyl
compounds and I(-alkyl-
and 3,4-dialkyl-substituted
repeated
using
pure acyl
enantfomsrically
C(n’-C.H.)Pe(CO)(PPh,)l. coniiguration acetaldehyde.
The essentially
S-msthoxy
by methyl
iodide.
f[alfi*
l
228.0’
Thus, the optically
we have unambiguously
resulting
complexes
complexes
1:l mixture
fS)-2
and-1
g-laotams,
containing
was treated
of B-hydroxy
treated
the above reactions
complexes
whose absolute
with ;-butylllthium
were 0-msthylated
with two equivalents
were
auxiliary
complex 2,
successively
and
oi a,B-dialkyl-substituted
the chiral
pure (Sl-(*I-acetyl
assigned,”
addition-alkylations
synthesis
and
and the
of n-butyllithlum
(c 0.29,
been deduced previously.
C,H,l)
(d.e.
Oxidative
> 1CO:l:l:l) decomplexation
whose relative of
complex -11 configuration was that
followed
Work-up gave the (S),f2Rl,(3R)-(+)-2.3-dimethylheptanoyl
(S1.(2R),(3R)-(+)-
-11 with bromine
as had in
S. G. D~nps ef al.
5130 dichloromethane
at -78’C
dimethylheptanamide
(Calfi
diastereoisomerically decomplexatlon agreement
purity
Similarly, puriflcatlon, lactam fi stable
of
isomer
Cc 0.69,
could
Finally, conversion
of
(S)-6.7 --
purity
to confirm to complexes
neither
configuration
-20 was
the
at the a-centre
(2R),(3Rl-(-I-
that
complex
as stated.
and then methyl diastereoisomer.
(3R),(U)-(-1-18,
that
(Sl-17 -
iodide
to
Without
the starting
(S),(2R),(3R)-(*)-ll
of
not previously
the (S)-E-crotonyl -
ii. MeCW
(Sl-(+I-acetyl
and (Sl-lJ,
known in optically configuration
as stated.
complex 5 in the
complexes
(S)-&l
were
iii.NaHIMd
lSl,l2Rl,(3R)-W~
2 PhEHZNHli ii. MeI
PhCl$NNH2
% ‘I
more
must accompany
was formed with high diastereo-
than 1OO:l and the absolute
the intermediacy
in
-20 must have
at the a- nor B-centres
epimerisation
the derived
of greater
i.
that
that
to the (3Rl,(4Sl-(-1-cis-3,4-dlmethyl-N-benzyl-6As no trace of the thermodynamically
cs,-g.l.
ii. MeOH
stereochemistry
benzylamide as a single
confirmed
in 421 yield.
i. +di
i.FltCH3NHLi
of
follows
This when combined with the fact
necessitates
has an optical in order
with bromine
pure and that
(>lOO:l:l:l)
form,
lithium
complex lJ
CHCl,))
be detected,
reaction.
complex 2 was optically selectivity
of
The amide (2R1,(3Rl-c-l-
and agaln
retention
than 1OO:l and the absolute
was decomplexed
-29.2’
the decomplexation
active
spectroscopy
It therefore
two equivalents
gave (2R),(3R)-(-)-N-banzyl-2,3-
in 81% yield.
with complete
cases.”
(S)-g-amino-a,B-dlmethyl
(S)-17 -
trans
reported
of greater
[Calb’
of benzylamlne
(c 1.23. C,H,))
-5.3'
had occurred
addition
gave the
l
pure by 300 MHz ‘H n.m.r.
procedure
with previously
an optical (S)-tj.1
and in the presence
0
t Ii
N-Ph
The luymmetlic synlhosis of &lactama subjected
to sodium hydride-induced
with recovered benzylamlde
starting
Oxidative
oomplex lJ
during
([a]b’
the deoomplexatlon
the dlastereotoplc
(the
faces
used In oomblnatlon
acyl
auxiliary
carbonyl
many electrophlles
(4S)-t-j-16 -
was obtained
as the sole
product.
must have an optical
purity
of greater
than
tandem addition
faoe)
pure acyl
attached
for
this
reaction
reaotlons
also
the asymetric
B-lactams
to the ohiral
can be used to quenoh the enolate of
these
complexes,
C(n‘-C.H,)Fe(CO)(PPh,)l ligands
of nucleophiles
and
4.
oompounds and 3,4-substituted
the scope
16 no raoemisatlon
Tt~e tuo new bonds are ?ormed -01s onto one of of the original carbon-carbon double bond. When
ooeplex
unhindered
wide range of E-a,g-unsaturated nucleophiles.
C,H,))
the stereocontrolled
iron
with enantlomerloally
the chiral
a,B-substituted
step,
demonstrate
to the E-orotonyl
of
(c 0.44,
configuration.
The above reactions
potential
together
of
1OG:l and the PS absolute electrophiles
143.0’
l
(S).(2S)-(+I-15 gave the (4S)-(-)-4-methyl-N-benzyl-g-lactam [alb’-34.5’ (c 3.0, MeOH)) in 651 yield. Since MeGHI, lit..”
(c 2.1,
is expected
was lsolated
material
decompleratlon
f[a]~‘-38.5°
Complex (S)-2
of methano1.l’
W-6.7 which as an inseparable mixture was treated with lithium -A single observable diastereoisoler of the (S).(2S)-(+)+Iby methanol.
followed
amino-g-methyl
elimination
5131
of high optloal auxiliary
generated
illustrate
synthesis purity.
Since
are avallable’0
by the Michael
the
of
addition
a
and since of
lithium
is extensive.
Exper lmental All
reactions
vacuum line
and purifications
and schlenk
Tetrahydrofuran(THF) distilled
was dried
from calcium
c-Wltylllthium
over
hydride
Unless
Perkln-Elmer
297 instrument.
otherwise
University
X-ray
crystal Cell
having
structure
approximate
Reflections
and reflection
merged to give [I
> 30(I)]
Crystal
4326 unique
Data, P2,,n
electron atomic
U - 2345.8 (established
density positions,
and an extinction shifts
x 0.20
mm. lhe scan range
from 0.9
(R,,g
factors All
from
reflections
measured every
hour
polarlsation
and
Lorentz,
and equivalent
reflections
of which 2842 were considered
to
were
be observed
analysis. monoclinic,
8 - 15.480
least
a OOQIO~overall
2 = 1a.904(4),
for
non-hydrogen
factor.
(Rw 0.046).
atoms),
for
an overall
and for
saale
respective
factor carbon
was terminated
each reflection
i.
space
parameters
on their
The refinement The weight
om-‘,
by Patterson
included
to “ride”
2 - 8.055(l)
A) 7.30
was solved
refinement
were allowed
temperature
o with II 0.038
The structure squares
(anisotropic
hydrogen ata
(2).
u (Ho-Ka = 0.71069
Mgm-‘.
absenoes).
full-matrix
temperature
than 0.1
0.04)
1.00 - 1.22)
Ho-Ka
upon the intensity.
depending
for
by
a orystal
c(u) was calculated
qin-’
to 6.7’
Three standard
factors
Z - 4, D, - 1.37
Final
in the w/20 scan mode for
The data were corrected
transmission
parameter.
were less
vere measured with graphite
x 0.18
wlth time.
frcm systematic
methods.
atoms and were assigned all
monoohaaated
Fl - 480.33, ii’,
were performed
Services.
intensities
reflections
CI,H,,OIPFe,
analyses
Analytical
MHz
were recorded
4
and used in the structure
6 - 95.63(2)‘. group
(relative
Mass spectra
(RS)-E-C(~‘-C.H.)Fe(CO)(PPh,)COCH-Cal
in the range 0 < 0 < 25’.
variation
on a
on Sruker WH300 (300.13
Elemental
operating
was
were used as supplled
as Nu.jol mulls
spectrometers.
Laboratory
standard
pressure.
between 67’C and 70’C.
ether)
in CDCl,,
FD techniques.
and the scan speed varied
were scanned effects”
0.78
using
Dlchlorcaethane
boiling
were recorded
MHz “P)
CAD-4P diffractometer
dimensions
tan 01’
showed no appreolable absorption
of
and dlstllled.
fraction
H in diethyl
spectra
101.26 using
ketyl
were recorded
and the Dyson Perrins
analysis
on an Enraf-Nonius
CO.95 + 0.35
MHz “C,
ZAB 2P instrument
parameters
radtation
infrared spectra
(1.5
atmosphere
were removed under reduced
to that
and methyllithium
N.m.r.
of Manchester
under a nitrogen
solvents
sodium benzophenone
stated,
‘H) and Sruker AM 250 (62.896 the
Nl
and hexane refers
(1.6t4 in hexane)
by Aldrich.
on a V.G. Uicrcmass
were performed
tube teohniques.*8
when
was
S. G. DA-
5132 calculated t,(X)]
from the Chebyshev series
where X - Fo/Fmax4’.
electron
density
Final
and a detailed
were perPormed with Atomic scattering
are listed
Preparation
of
in Table
in Table
failed
1.
Final
to reveal
atomic
procedure
for
by subsequent
(25 ml) at -78’C
according
to give
any systematic Tables,
and removal
chromatography determine
Volume IV.”
described
of alkylllthiums
with electrophiles
equivalents)
of solvent through
on alumina
H, 6.2: cm-’
P, 6.2.
alumina
(C-O)
‘H n.m.r.
i
ether
analysed
6 7.6
COCHMs). 0.53
(3H, d,
(d,
Jpc
(s,
Ph Cpara),
21.6
31.5
- 7.3
(s.
127.9
Me),
17.1
(-78’C;
He).
C. 70.6;
(s.
with 60:80
Elution
4.43
Jl,a
JpH
1.4 Hz, &HI),
(3H. d, Jl,a
2.77
(lH,
J,,2
were purified
upon removal
of
dlastereoisomer.
Jpc
31.4
(s,
Ph Cpara),
(s,
CH), 31.3
“P{‘H)
Hz. CEO). 136.9 127.9 (s.
n.m.r.
(d,
CH,),
(d.
Jpc 9.4 30.0
85.2
0.91
6.8 Hz. Me); 133.5
(s,
(d.
&HI),
n.m.r.
Cl:11 gave
(Found:
6 71.7:
2.80
(1Hs dq.
(3H, d,
“C(‘H)
Jl.2
n.m.r.
(s.
COCH). 26.4
( Found :
with diethyl
c, 71.55:
J,,,
2.91,
(s.
128.0
(d,
2.34
m/z 510 (M’).
C,,H,,FeO,P
‘H n.m.r.
HZ. Ph Cipso),
Hz, Ph Cmeta).
85.2
CH1). 23.1
CH,).
requires
6 7.6 - 7.3 - 0.61
(d,
-m/z 538 (M+).
133.4
(s,
(d.
C,H,).
18.2
(s,
mixture
C, 71.7;
(15H, m. Ph),
H, 6.75: 4.42
(7H. m. CH(CH,),). 0.47 n.m.r.
JPC 9.5 Hx. Ph Cortho)t
72.7 Me).
(d, 14.3
JpC 4.4 (s.
(5H, d. 0.97 (3H, de 6 221.2 129.4
Hx. COCH). 32.4
Be).
11.8
(se Me);
H, 6.9;
JPC 42.9
(s,
6.6 Hx. Cme):
HZ, Ph Cipso). (s,
- 7.3
(15H. m, Ph),
JAB 16.6 Hz, COCH,), 1.70
(3H, d, J,.,
CH,) 23.0
6 7.6
‘H n.m.r.
(C-O);
(2H, ABX system. 0.41
13
gave complex -13 (821) as a >180:1 mixture Of diastereoisomers. C,,H,,FeO,P requires C. 71.4; H, 6.55: P, 5.75%); vmax P, 5.8.
Jpc 9.3 Hz, Ph Cmeta) 85.3
CH), 29.3
129.5 CHMe,),
ether
1620 s cm-’
7.0 Hz, CH&).
CEO), 136.7
6 221.2
6 71.8:
1905 vs (CEO), C.H,),
Jt,s
7.3 Hz,
complex 11 (93%) as a 160:1:<1:<1
P, 5.5.
(C-O);
(s,
C. 70.7;
JPC 9.4 Hx, Ph Cortho),
72.4
7.3 Hz. 3.0 Hz, COCH), 1.26
-m/z 552 (M+). (RS/SR)-C(n’-C,H,)Fe(CO)(PPh,)COCH,CH(Me)n-Bul Elution
to
fi.
H, 6.8:
JpC 42.3
(s,
solvents
vmax 1900 vs (CEO), 1612 s
7.4 Hz, CONMe major diastereoisomer), 0.82 (3H, t, J,,2 6.9 Hz, CH&), 6.9 Hz, COCHMe minor diastereolsomer); ‘“C(‘H) (3H. d. J,,, -
J,,,
by
hexane (-3O’C).
from
6.8 Hz, CHHH), 0.23
(d.
(s,
Warming to room
(5H, d. JPH 1.3 Hx, C.Hs),
(3H, d, J,,,
ether
C, 72.0: dq.
of
was added
2h).
6.8 Hz, 2.8 Hz. Cyea),
“P(‘H)
vmax 1908 vs (CEO), 1598 s cm-’
P. 5.63);
the addition
with dichloromethane
complexes
P, 6.1s);
HZ, Ph Cipe,c)r
Me);
petrol-diethyl ( Found :
(-78’C;
as a single
(RSS/SRR)-C(n’-C,H.)Fe(CO)(PPh,)COCH(He)CH(Me)~-Bu~ of diastereolsomers.
2h for
spectroscopy
needles
H, 6.1;
(15H, m, Ph),
JpC 42.1
10.8
11 and 13 500 me, 1.04 mmOl) in THF
(2 equivalents)
The product
by ‘H n.m.r.
JpC 9.3 Hx, Ph Cmeta),
(d,
(s,
(d,
9,
which was extracted
as orange
6.9 HZ, Me), 0.33
Jl,z
in
2.
(1H. dseptets.
HZ, CZO). 136.9
oil
gave complex 2 (60s)
requires
7.2 Hz. 2.8 Hz, COCH). 1.41
bond lengths
previously.‘o
complexes
stirring
(Grade V).
and obtained
C,,H,IFeO,P
Selected
to E-C(n*-C.H,)Fe(CO)(PPh,)COCH-CHMel
to give
After
(RS/SR)-[(n’-C,H,)Fe(CO)(PPh,)COCH(Me)CHMe,l with dlethyl
calculations
with e.s.d.‘s
was added to complex 4 (typically
gave an orange
(Grade I),
diastereoselectivites
Elution
All
4.
a dark red solution.
(3 x 10 ml) and filtered
+ 95.21 residual
VAX 111750 COmpUter.”
coordinates
and -40°C; 2h for methylllthlum), the electrophile -n-butyllithium dropwise to the solution at -78’~ and the mixture further stirred temperature
t,(X)
errors.
Crystallography
positional
to the procedure
addition
reaction
(1.2
+ 579.68
showed no significant
1.
the Michael
The alkylllthlum
t,(X)
synthesis
on the Chemical
E-[(n’-C,H,)Fe(CO)(PPh,)COCH-CHMel
Complex ‘( was prepared
4 followed
analysis
1435.25
l
Fourier
were taken from International
are given
parentheses
General
u - C955.87 t,(X) difference
the CRYSTALSpackage
factors
and bond angles
et al.
CH,),
133.4
(s,
C,H.),
19.7
(s,
(d.
“CilH)
- 0.89 n.m.r.
6 220.8
JpC 9.5 Hx, Ph Cortho),
74.1 Me),
(d, 14.1
JpC 4.8 (s.
Me);
4.40
(5H, d,
JPH 1.1 Hx,
(7H. m, CH(CH,),), (d.
129.6
(s.
nZ. COCH,), 36.8 “PI’H)
n.m.r.
0.86
JpC 31.4
(3H, t. Hz.
Ph Cpara). (s.
CHz), 29.3
6 72.4;
5133
The asymmetric synthesis of fi-lactams
Oxldatlve
deccoglexation
of
erythro-2,3-dimathylheptanoic
Bromine (0.1
ml,
12
acid
1.9 lmol)
in THF (2 ml) uaa added dropwise
complex -11 (566 mg, 1.03 mmol) in THF (10 ml) containing After stirring (O’C; 3h). a saturated Na,S,O, solution. Upon further
rewved.
was extracted
addition
with diethyl
of water
(20 ml) and washed successively extracts pale
dlethyl
ether
1.47-0.82
NaHCO, (aq)
(20 ml) and dried
‘H n.m.r.
0.87
(CH),
32.9
1.11
(3H, t, (CH,),
acid
6 2.35
J,,,
(3H, d,
JIIt
29.2
(CH,),
22.8
17.1
n.m.r.
(Me).
(Me).
The
gave a
upon elutlon
vmax (CHCl,)
he
(3 x 15 ml).
Removal of solvent
with
3500 br (0-H).
1.75
(lH,
m, C$He)CH,),
(3H, d,
J1,.
6.8 Hz,
6 181.6
14.0
solution
(2 x 20 ml).
ether
to give
6.7 Hz, Cl$O,H).
“C(‘Hl
(CH,),
Na,SO,).
_ Hz, CH(He)CO,H), 0.92
7.1
6.9 Hz, CH,Cli,);
Jl,,
of
was concentrated
with dlethyl
12 (44 mg, 271).1’
quintet,
(lH,
the aquwus
(20 ml) and then water
(60H-Merck)
gel
solution
a dark brown
(1 ml) was added and the THF
(pH 1).
green solution
(anhydrous
on silica
(O’C)
ml) to give
solution
(pH 1) and extracted
erythro-2.3-dlmethylheptanolc
(6H, m, (CH,),).
CH(Me)CH,), 35.8
with saturated
were reacidified
011 which was chromatographed
1700 vs cm-1 (C-0);
(aq)
to a cooled
(0.4
(15 ml) and acidification The resultant
were uashed with water
yellow
water
(3 x 20 ml).
ether
combined aqueous washings
11 to
(R99/SRR)-C(~‘-C.H.)Fe(CO)(PPh.)COCH(~)Cn(~e)n-WIl
(CO,H),
13.6
44.5
Me);
(CHCO,H),
m/z
(CI/NH,)
176
(n+ + 18). Oeneral
procedure
for
the Michael
addition
E-[(~‘-C.H.)~(CO)(PPh.)COCH-C~) complexes
n-Butylllthlum to give
(0.4
ml. 0.64
an intense
and added dropwise
red solution. mixture orange
lithium
benzylamlde
by subsequent
to
reaction
with electrophiles
to give
15 and 17
at -2O’C -78’C
of
4 followed
After
further solid
complexes
stirring
stirred
(-78’C;
(-78’C;
were purified
solution.
The solution
to complex 2 (250 mg, 0.52 2h),
lh).
which was dissolved
upon removal
mmol) was added to benzylamine
purple
the electrophlle
in dlchlorcmethane
to determine
mmol) in THF (20 ml)
(-2O’C;
cooled
lh),
to
rmool) in THF (30 ml) at -78*C to give (4 equivalents)
Warming to roo11 temperature
by chromatography
of solvents
(70 mg, 0.66
was stirred
on alumina
through
(Orade I),
diastereoselectlvities
was added and the
and removal
and filtered
a deep
of solvent
Celite.
analysed
by ‘H n.m.r.
and obtained
gave an
The product spectroscopy
as orange needles
Lola
dlchlorcmethane-hexane. (RR/SS)-[(~‘-C,H.)Fe(CO)(PPh,)COCH,CH(ne)NHCH,Phl Elutlon
with dlchloromethane-ethyl
dlaatereolscmer.
(Found:
H, 5.8;
P, 5.31);
6 7.6
N. 2.4; -7.2
C&Ph). 6.1
3.08,
2.68
Hz, Me);
42.6
“CIIHl
128.1
C, 71.6:
H, 5.8;
vmax 3300 w,br
4.40
(5H. d,
(2H, ABX system, n.m.r.
Hz, Ph Cipso)t
Cortho), 5.4
(20H, m, Ph),
133.4
6 220.5 (d,
(de JPC 8.5
Hz, COCH,). 51.3
(s,
(10:9:1)
N, 2.4; (N-H),
Jm
18.3
(d,
JPC 31.4
JpC 9.4
1910 vs (CEO). 1600 s cm-’
(s.
3.69,
Hz. CIO),
Hz, Ph Cortho),
49.7
complex -15 (9@) as a single requires C, 71.55;
C,,H,,FeNO,P 3.56
Hz, COCH,). 2.64
126.6
gave
P, 5.0.
JPH 1.1 Hz, C,H,),
HZ. Ph C,ta)r
gHIPh),
fi.
acetate-methanol
(9,
(lH,
141.1
129.7
(s,
(s,
Me);
Jm 12.9 (3H, d,
CH,Ph Cipso).
Ph Cpara)r
CHzPh Cpera)r
gHMe), 20.0
m, CI$ee). 0.68 (a,
85.4
128.2
(6,
“P(‘Hl
‘H n.m.r.
(C-0) ;
(2H, AB system,
136.5 (s,
CIH,),
n.m.r.
Hz,
J,,, (d,
JpC
CH,Ph
73.2
(d,
6 72.2;
JPC
-m/z 587
@I+). (RSR/SRS)-C(II’-C,H,)Fe(CO)(PPh,)COCH(ne)CH(Me)NHCH,PhJ Elutlcn
with dichloromethane-ethyl
dlastereolsooer.
(Found:
H, 6.0;
P, 5.151):
6 7.5
N, 2.3; -7.2
CbPh), JIIl
2.68
6.4
136.4
(2OH. m, Ph),
(d,
JpC 42.6
JPC 9.1
(s.
cH(Me)N),
(8,
H, 6.0;
N, 2.4;
vmax 3330 w (N-H),
4-44
(5H. d,
“C(‘H)
126.1
gH.Ph),
133.2
17.5
P, 5.1.
6 220.7 (d,
1.12
(d,
JpC 9.5
CH,Ph Cpara), (8,
CH@)N).
gave complex -17 (91%) as a single C,,H,,FeNO,P requires C. 71.9;
1910 vs (CEO), 1580 s cm-1 (c-o)8
(1H, m, C$Hee)N),
(s,
-17. (10:9x1)
J pR 1.2 Hz. C,H,),
n.m.r.
Rx, Ph CILIA).
Hz, Ph C,ta), 51.1
C, 71.9;
m. COCH), 1.72
Hz, COCH(gs)):
(d,
601 CM+).
(lH,
acetate-methanol
3.67,
3.32
(3H, d,
JPC 31.5
Jl,,
7.5
85.5
(a, (a,
C.H.),
129.5 71.5
COCH(k));
Jm 13.9
Hz. CHo(e)N),
Hz, CEO), 141.3
Hz. Ph Corthc),
10.0
‘H n.m.r.
(2H. AB system, (a,
(a.
(d. “P(‘Hl
0.54
Hz, (3H. d.
CH,Ph Cipsc).
Ph Cpara),
JpC 5.2 n.m.r.
127.9
Hz. COCH), 51.2 6 70.7;
-m/x
S. G. DAMBPet ul.
5134
General
procedure
for
the oxldatlve
Bromine (2 equivalents) B-amino acyl solution.
complex
(typicrally
After stirring
room temperature. distillation
decomplexatlon
in dichloromethane
500 mg) in dichloromethane
(-78°C;
lh),
triethylamine
Removal of solvent
of
this
which was further
residue
purified
(below
under reduced
glutlon
JAB 15.2
system. 2.1
with aoetone-diethyl Hz, C&Ph),
HZ, JgX cis
(2H. d. (lH, (C-0).
15 Hz, C&Ph).
Jl,a
dd,
2.5
J,,,
136.1
(sHHe),44.4
3.58 3.56
(CH,),
128.7
44.2
18.5
m, CEe).
(Me);
(neat) 15.2
with acetone-diethyl
1740 s cm-’ Hz, C&.Ph),
COC$he)),
3.63
1.16
(5H, m. Ph),
(C-0);
4.52,
3.13
(1H. III. J,,,
He)];
l’Cf*HI
(3H, d,
(lH, JIII
JAB 14.4
6 7.3
(5H. s,
4.9 Hz, 14.5
dd, J1,,
“CI’HJ
(Ph Cortho/C,ta)B
HZ, JgX trans
Ph),
4.65,
4.06
Hz, COCH,). 2.48
n.m.r.
127.6
6 166.8
(Ph Cpara),
oil. -18 (69%) as a colourless (5H, m, Ph), 4.59, 4.04 (2H, AB system,
- 7.2
Hz. CiH(He)N), 3.22
136.2
(Ph Cpara 1, 50.5
(3H, d,
Hz, C&Ph),
7.5 Hz, 6.0 Hz, COCH), 1.11 127.6
[lit.”
gave B-laotam
Hz. 5.4
15.5
(C-O),
the crude B-lactam
(2H. ABX system,
6 Hz. Me)];
128.2
7.6 Hz, COCH(M_a)). 1.07
6 171.2
warmed to
path
47.0
fi.
(1:9)
6.4
J,,,
Short
m/z 175 (H*).
6 7.4
(2H, d, J,,,
n.m.r.
(CH@s)N);
dq,
JI,,
4.00
(Ph Cmeta/Cortho)r 8.8
‘H n.m.r.
(lH,
(3H. d,
ether
2.54
3.05
(*)-cis-3,4-Dimethyl-l-(phenylmethyl)-azetidin-2-one Elution
the
(60H-Merck).
6.1 Hz, he)
(Ph Cmeta/Cortho)r
(CH,).
of
a brown-red
oil. vmax -16 (68%) as a colourless 6 7.3 - 7.2 (5H. m. Ph). 4.60. 4.11 (2H. AB
3.07,
(3H, d, J,,,
Hz, 14.5 Hz, COCH,). 1.17
(Ph Cipso),
green solid.
0.1 mmHg) afforded
gel
‘H n.m.r.
(1H. m, Cfle), (lH,
to give
was added and the mixture
(lOO°C,
on silica
1750 cm-‘I:
4.9 HZ, COCH,), 1.22
(excess)
pressure
to a solution
(15 ml) at -78’C
-16. (1:9) gave B-lactam
ether
1750 s cm-' (C-0) [lit.”
15 and 17 to 8-lactaw
2O’C) gave a tacky
by chromatography
(i)-4-hethyl-l-(phenylmethyl)-azetidin-2-one (neat)
of complexes
(2 ml) was added dropwise
3.51
(lH,
(3H, d, JI,a
(Ph Cipso),
Jl,,
dq,
m, J,,,
J,,,
6.3
7.5 Hz, he).
128.7
(COCH), 47.0
(lH,
7.6
6.4 Hz, CH(W)N) 1.01
43.9
Hz, 5.4 Hz,
[lit”
6 7.23
Hz, 6.0 Hz, C$he)N), (3H. d.
(Ph Cortho/Cmeta),
(CH(He)N),
vmax JAB
J1,,
6.3 Hz,
128.2
(CH,Ph),
13.5
(COCH(&)),
m/z 189 (M+).
Epimerlsation
of
~~~-ois-3,4-Dimethyl-l-~phenylmethyl~-azetidin-2-one
18
The -cis-8-lactam (10 mg, 0.09 mmol) in -18 (80 mg. 0.42 mmol) and potassium tert-butoxide The reaotlon mixture was poured into water (5 ml) tart-butanol (4 ml) were heated (5O’C; 15 h). and extracted
with diethyl
upon evaporation mixture
of -18 and its
system,
JAB 15.2
1.5 Hz, CljCH,). s,
Ph),
(lH,
dq,
4.62,
Hz. C&Ph),
3.15
IH n.m.r. (lH.dq,
(3H, d, J,,,
(2H, AB system,
6.1
Jl,z
(0.6
to give
nvwl)
to revert
removal
of solvent
filtered
through
upon removal spectrum
J,,,
of
gave an orange alumina
solvent
with that
ml, 0.80
diastereoisomer
(5H. III, Ph),
Hz, 2.0 Hz, C&H,),
1.20
(3H.d.
J1,*
3.16
(lH,dq.
6 Hz, CH,),
After
armol).
2.73
4.07
(lH.dq.
(2H, AB J1,,
6.1 Hz, CH,) [lit.” J1,,
1.17
6 HZ
(3H, d.
and
as a I:2 7.4
Hz.
6 7.28
(5H.
, 2 HZ, NCH). 2.74
J,,*
6 Hz, CH,)].
11 from both
(RS/SR)-
and
colour
2.5 h),
(-78’C; further
stirred
(-78’C:
iodide 3h).
with dlchloromethane
diastereoisomer
r#nol) in THF (20 ml) (0.5
ml;
Addition
caused
Warming to room temperature
instantaneously.
which was extracted
methyl
by comparison
and
(2 x 20 ml) and
as an orange or its
powder
‘H n.m.r.
sample.
was repeated
by ‘H n.m.r.
4.61.
Complex -11 (158 mg, 77%) was obtained
(Grade VI.
The product
stirring
and the mixture oil
Na,SO,)
6 and 7
and shown to be single
of an authentic
(anhydrous spectroscopy
mmol) was added to complex 5 (190 mg. 0.37
back to an orange
The above procedure (0.5
ml. 0.96
a dark red solution.
was added in one portion
the solution
- 7.2
JAB 15 HZ, C& Ph), (3H, d,
were dried by ‘H n.m.r.
(RSS/SRR)-[(q’-C.H.)Fe(CO)(PPh,)COCH(ne~CH(Me)n-Bu]
;-Butyllithium 8.03
6 7.4
7.4 HZ, CH,).
(RR/SS)-[(n’-C.H,)Fe(CO)(PPh,)COCH,CH(Ol4e)Fle~
at -78’C
extracts
011 (75 mg, 951) identified
6 Hz, 2 Hz, CHCO). 1.25 oi
The ether
(3 x 4 ml).
trans-eplmer.”
1.27
4.05
J,,,
Preparation
ether
gave a colourless
with complex I(150
mg. 0.29
mmol) and g-butyllithium
oomplex -11 (144 mg, 89%) was again
spectroscopy.
shown to consist
of a single
Preparation
of
(RS/SR)-C(n‘-C.H.)Pe(CO)(PPh,)COCH(~e)C~,l
L:(n‘-C.H,)Fe(CO)(PPh,)COCH.CH(OCk).~ Methyllithium After
The solution,
give
a light
orange
and removal filtered
recoollng
of solvent
through
diethyl
ether
methyl oil
of
(SR)-
stirred
(2.1
and the resulting
which was extracted
ml,
3.1 mmcl) was added
dark red mixture
was added and the solution dlchloromethane
and chrcmatographed
(1:l)
Elutlon
with dlchlorcmethane-methanol
gave starting B-hydroxy
by comparison with sodiw
0.5h).
single
Addition
through yellow
material
complexes of
After
(1O:l)
(SS)-
of methyl
alumina
of
values
through
(1.1
ml,
16.9 mmol),
Concentration
(Grade I).
A single
of
band was eluted
of
solvent
(S)-E-[(n*-C,H,)Fe(CO)(PPh,)COCH-CHt4el
extraction solution
powder (700 mg) identified 2”
of the (1.04
(2O’C;
952) was
stirred 40h) and
(3 x 30 ml) and
on alumina
identified
g,
This mixture
(Grade I)
as a 1:1.4
gave a
mixture
of
spectroscopy.”
C(n‘-C,H,)Fe(CO)(PPh,)(150 mg, 6.3 mmol) and the with dichloromethane
(3 x 10 ml) and
which was chromatographed acetate
by ‘H n.m.r.
and starting
(2R),(3R)-(-)-N-benzyl-2,3-dimethylheptanamlde
Thus (SRI-iand (0.4
sample.
(1:l)
spectroscopy
material&z.
on alumina which upon as a 2:l
This mixture
purification.
(ss)-[(no-C.H,)Fe(CO)(PPh,)COCH,CH(OE(e)nel
iodide
which
4
20
(S),(2R),(3R)-(*)-[:(rl’-C,H,)Fe(CO)(PPh,)COCH(He)CH(~te)~-Bul above.
stirring
with dlchlorcmethane-ethyl
of
of
gave an orange
solution
mixture values.’
1 by ‘H n.m.r.
and (SS)-
(Grade V) gave an orange
removal
Preparation
fiand
(4:l)
mg. 1.67 mm011 and sodium hydride
yellow
further
further
and chromatography
(SRI-
mixture
was used without
with an authentic
with dichloromethane
acetate
ml)
with
THF (30 ml) was added and the reaction
48h). Removal of solvent,
alumina
extraction
diastereolsomerlc
011 which was extracted
ml,
(0.5
with dichloromethane-ethyl
with the literature
with dichloromethane-ethyl
I(855
(2O’C;
Elution
(0.4
methanol
(Grade V) gave an orange
by comparison
(S)-E-[(n’-C.H.)Fe(CO)(PPh.)COCH=CHMe~
stirred
2h),
and (SR)-[(I’-C,H,)Fe(CO)(PPh,)COCH,CH(OH)He]
iodide
(Grade V).
band eluted
of acetaldehyde
(-78’C;
Removal of solvents,
a 1.4:1
gave
(200 mg, 8.3 mmol),
gave an orange
COCH,CH(Ot4e)Me]gand filtration
with as shown
g, 2.2 mrocl) in THP (30 ml) at
(1.0
stirring
(Grade I).
1 identiiled
THF (20 ml) was added to the mixture reaction
dlastereoiscmer
A solution
lh).
further
(SRI- and (ss)-[(n’-C,H,)Fe(CO)(PPh,)COCH,CH(OHe)Mel Preparation
(2 x 20 ml) and
gave upon elutlon
6 and 7 from
(9)-(+)-z”
through alumina
on alumina
the spectroscopic
hydride
of solvents
filtered
dichlcrowtthane
(Grade I)
50%) as a single
(-78’C;
warmed to room temperature.
acetate
corresponding
to
stirred
(3 x 20 ml) and iiltratlon
was concentrated
(20°C,
with
on alumina
to
Warming to rocm temperature
5
7.2 mmcl) in THF (2 ml) was added dropwise.
removal
became dark red in
(2h),
(-78OC; 2h).
complex 2 (124 qg,
of solvent
mmol) in THF
6.42 mmol) was added in one portion
and (~)-C(~g-C.H.)Pe(CO)(PPh.)COCH,CH(One)~l
n-Butyllithium
combined
and stirring
ml,
Chromatography
(Grade VI.
(S)-(+)-[(n’-C.H.)Pe(CO)(PPh.)C~l
identified
(0.4
(255 mg, 0.48
spectroscopy.
Preparation
-78’~
iodide
whioh was further
gave an orange
alumina
and removal
by ‘H n.m.r.
to complex -19 ”
upon warming to -40°C
(-78’C).
solution
9 from
19
(1.3 ml, 2.02 mmol) was added
(20 ml) at -78’C. colour .
5135
asymmstric syllthcsis of j%ctams
The
(W-1
aand
(356 mg, 0.70
cwas
1 by an identical
mpol),
fi-butylllthium
prepared
procedure (1.0
ml, 6.4 mmol) gave (S),(2R),(3R)-(*)-x(317 mg, 81%), Calb’
ml,
from (SRI-
to that
and
described
1.6 mmol) and methyl
+ 228.0' (c, 0.29,
(2 ml) was added dropwiseto a solutionof C,H.). Bromine (0.04ml. 0.78 mmol) in dlchloromethane (S).(2R),(3R)-(+I-=(317 mg. 0.57 mmol) in dichloromethane (15 ml) at -4O’C to give a dark brown solutlon.
After
stirring
(-4O’C;
lh),
benzylamine
(0.13
ml,
1.2 mmol) was added and the mixture
5136
S. G. D~nas et al.
narmed to room temperature. (60H-Herck).
Elution
solid
identified
40:60
petrol-diethyl
The solution
with 40:60
was concentrated
petrol-diethyl
ether
as [(I’-C,H,)Fe(CO)(PPh,)Brl ether
(1:2)
C,,H,,NO
(c~cl,)
(2H. m. C&Ph). Jltl
requires
3450 m (N-H), 7.0
2.02
Preparation
of
of solvent
Thus, (1.4
[albc
as a single
to that
of
2.75
mixture
described
benzylamide
mm011 to give
0.89
for
0.69,
(106 me, 65%).
(S)-?
generated
Oxidative
described
and (SR)-5
identified
(1.5
1.23.
C,H,);
5.72
vmax
(lH,
br,
NH), 4.45
1.14
7.0 Hz, CH&s);
of lithium
from benzylamine
iodide
(0.4
(3H, d.
e
benzylamide
(0.35
ml,
following
3.2 mm011 and
(c 2.1.
(SR)-5
x
the general
and
(153 mg,
procedure
-18 (20 mg, 4211, synthesised above.
16 lithium
benzylamide
2.4 mmol),
ml,
with an authentic
generated
from benzylamlne
and methanol
(0.6
previously.
Work-up gave
12 (690 mg. 81%).
described
to oomplex if
ml, 6.4 mmol) was added to
(700 mg) obtained
by oomparison
-16 synthesised
Acknowledgements:
with
18
deccmplexation
above,
- (W-1
procedure
Cala’ -38.5’
to (i)-
(c,
J,,,
Elution
H, 10.4;
(S)-[(n’-C,H,)Fe(CO)(PPh,)COCH04e)CH(HelNHCH,Ph~
mmol) and ;-butyllithium
the general
respects
C, 77.5;
(7H, m, CH(CH,),).
(3H, t.
the addition
(4S)-(-)-4-methyl-N-bensyl-6-laotam
of
sample. of
(5H, m, Ph),
(3R),(4S)-(-)-cis-3,4-dimethyl-N-benzyl-B-lactam CHCl,) identical in all respects to (i)-18-
the procedure
C.H.)
following
I.H.D-H,
- 5.3’
6 7.36-7.26
6.7 Hz, CH&),
C(rl”-C,H,)Fe(CO)(PPh,)COCH,CH(He)NHCH,Phl (c 0.44,
[alfj’
(Found:
Hz, COCH), 1.70-1.00
2.24 mrcol). and methyl
diastereoisomer.
c,
Following 2:l
JI,,
7.1
81%).
above gave the
-29.2’
ml,
N, 5.7%;
‘H n.m.r. J,,l
(3H, d,
lithium ml,
(501 qg, 0.98
Preparation (0.3
H. 10.2;
cO(C-0);
quintet,
procedure
was followed.
261)
20 (114 qg,
crystals
gel
gave a green
91 04+-156).
g-butyllithium
described
3
on silica
of solvent
with an authentic
gave white
(3R).(4S)-(-)-ois-3,4-dlmethyl-N-bensyl-B-lactam
An identical
(W-1
(lH,
Hz, CHMM), 0.91
(ACE/NH,) 247 &I+),
C, 77.7;
1660
and removal
by comparison
and removal
(2R),(3R)-(-)-N-benzyl-2,3-dimethylheptanamide N, 5.6.
and chromatographed
(2:l)
[ala1
(S),(2S)-(*I-
143.0’
l
sample.
ml) was added to the
Oxidative
decomplexation
above gave the (4S)-(-)-4-methyl-N-benzyl-6-lactam
HeOH) (lit.,az
[alb’
-34.5’
(c 3.0.
-16
MeOH)) identical
in all
previously.
We thank the SERC for
a studentship
(to
J.C.W.)
and financial
support
(to
K.H.S. and R.H.J.).
References 1.
C.J. Baird and S.G. Davies, S.G.
Davies,
and K. Prout.
S.G.
Davies,
Tetrahedron
J. Chem. Sot.,
and K. Prout.
Tetrahedron
L&t.,
J.L. 2.
Lett.,
J. Chem. Sot.,
H.E. Welker,
Tetrahedron
Brown6 S.G.
L&t.,
1984, 25.
V. Goedken.
J. Am. Chem. Sot. ,1984.
S.G.
Davies
and J.C.
4.
S.G.
Davies,
R.J.C.
Easton,
Lett..
106,
4341
S.L.
L.S.
Baird,
J.A.
K. Broadley
Dordor. S.G.
and P. Warner,
Brown, S.G.
P. Warner,
Davies
P. Warner,
Bandy,
and
and P. Warner,
R.H. Jones,
Davies,
D.F.
and Foster,
623. 194;
Liebeskind,
L.S.
Liebeskind
M.E. Welker,
and and
441.
J. Chem. Sm., K.H. Sutton,
213;
1983, 2.
i
I.H.
Davies,
1986, 2,
Organometallics,
3.
Walker,
1446;
G.J.
1202;
I.M. Dordor-Hedgeoock,
Chem., 1985, 2,
S.L.
Tetrahedron
and H.E. Nelker,
Davies,
S.G. .Daviea,
Chem. Commun., 1965,
Seeman, and P. Warner,
L.S. Liebeskind
4815;
S.G.
1743;
956;
J. Organometal.
1985, 6,
Chem., 1983, 21(8, Cl; Chem. Commun., 1983,
1904. 25,
Chem. Common., 1984,
R.H. Jones, K. Prout,
J. Organometal. J. Chem. Sot.,
Chem. Commun., 1985,
J.C.
Walker,
209.
and R.H. Jones,
submitted
for
publication. 5.
L.S. Liebeskind
6.
J.D.
Morrison
‘Asymmetric
and M.E. Welker,
Vol.
3. 1984,
pp.
252-267.
Tetrahedron
Synthesis’,
I.&t.,
Academic Press,
1985, 26,
3079.
New York,
Vo1.2,
1983,
PP. 201-241
and
Theasymm~tricsynthesis
7.
5137
offl-lactama
K. Tomioka.F. Masumi, T. Yamashlta,and K. Koga, TetrahedronI&t., 1984,25, 333; K. Tomioka,H. Kawasaki. Y. Iltaka.and K. Koga, TetrahedronLett.. 1985.a. K. Tomioka,H. Kawasaki,and K. Koga, TetrahedronL&t.,
1985, 26,
3027;
903;
A.I. kvers
and
B.A. Barner. J. Org. Chem., 1986,51, 120; J. Nokami,T. Ono, and S. Wakabayshi. TetrahedronLett.. 1985,26, 1985; Y. Fukutani.K. Maruka,and H. Ysmamoto,Tetrahedron Lett.. 1984,25, 5911: C. Iwata,K. Hattori,S. Uchida,and T. Imanishi.TetrahedronL&t., 1984,3. 2995; C. Iuata,M. Fujlta,K. Hattorl,and S. Uchida, TetrahedronLett., 1985.26, 2221; O.H. Posner and E. Aslrvatham,J. Org. Chem., 1985,50, 2589: G.H. Posner and M. Hulce, TetrahedronL&t., 1984,5
379; C.H. Posner.T.P. Kogan, and M. Hulce, Tetrahedron
1984,25. 383; G.H. Posner.L.L. Frye, and M. Hulce, Tetrahedron,1984,9, 1401. J. Fujiwara,Y. Fukutani,M. Hasegaua.K. Maruoka,and H. Yamamoto.J. Am. Chem. Sot.. 1984.
e,
a.
106, 5004; S. Hashimoto,N. Komeshima,S. Yamada,and K. Koga, Chem. Pharm. Bull., 1979, 2437; T. Mukalyamaand N. Iuasawa,Chem. Lett., 1981, 913; T. Kogure and E.L. Eliel. J. Org. Chem., 1984,49. 576; P. Mangeney,A. Alexakis,and J.F. Normant,TetrahedronLett.,
3,
1983.3 373; T. Hukaiyama,T. Takeda,and K. Fuimoto. Bull. Chem. Sot. Jpn., 1978,II, 3368; A.I. Meyers, R.K. Smith, and C.E. Whitten,J. Org. Chem.. 1979. 3, 2250; K. Soai, H. Machida,and A. Ookawa.J. Chem. Sot., Chem. Commun.,1985, 469; K. Tomioka.T. Sueuaga,and K. Koga, TetrahedronLett., 1986,3, 9.
369.
W. Oppolzerand H.J. Loher, Helv. Chlm.
Acta..
1981,
&
2808;
W.
Oppolaer,R. Moretti,T.
Godel, A Meunier,and H. Loher, TetrahedronLett., 1983,211,4971; W. Oppolzer,P. Dudfield, T. Stevenson,and T. Godel, Helv. Chim. Acta., 1985, TetrahedronLett.. 1986,3,
1139;
68,
212; W. Oppolzerand T. Stevenson,
G. Helmchenand G. Wegner. TetrahedronL&t., 1985,6,
6051. 10.
S.G. Davies, R.J.C. Easton,J.C. Walker,and P. Warner, J. Organometal.Chem.. 1985,296, c40; S.G. Davies, R.J.C Easton.J.C. Walker,and P. Warner, Tetrahedron,1986,r(2,175.
11.
L.S. Liebeskind,R.W. Fengl, and M.E. Welker, TetrahedronLett., 1985,s
12.
S.G. Davies, I.M. Dordor, J.C. Walker,and P. Warner, TetrahedronLett., 1984,25. 1333.
13.
3075.
S.G. Davies and J.I. Seeman,TetrahedronLett., 1984,25, 1845; S.G. Davies, J.I. Seeman, and I. H. Williams,TetrahedronLett.. 1986,21, 619.
14. 15.
S.G. Davies and J.I. Seeman. unpublishedresults. Y. Yamamotoand K. Maruyama.J. Chem. Sot., Chem. Co-n.,
1984. 904. We thank Professor 2,3-dimethylheptanoic
Yamamotofor providingspectroscopicdata on erythro-and 16. 17.
S.R. Berryhilland M. Rosenblum.J. Org. Chem.. 1980, F.F. Blicke and W.A. Gould, J. Org. Chem., 1958,3,
acid.
'15, 1984.
1102; I. Ojima and H.B. Kuon.
Chem. Lett., 1985, 1327. 18.
P.K. Wong, M. Madhavarao.D.F. Marten,and M. Rosenblum,J. Am. Chem. Sot., 1977,99, 2823.
19.
N. Aktogu,H. Felkin,G.J. Baird, S.G. Davies,and 0. Watts, J. Organometal.Chem., 1984, 262, 49.
20.
S.G. Davies, I.M. Dordor-Hedgecock, K.H. Sutton,J.C. Walker, C. Bourne,R.H. Jones, and K. Prout, J. Chem. Sot., Chem. Comuun.,1986. 607.
21.
R.W. Johnsonand R.G. Pearson,J. Chem. Sot., Chem. C-n.
1970, 986; S.G. Davies,
I.M. Dordor-Hedgecock, and P. Warner, TetrahedronL&t., 1985,26, 2125; P.W. Ambler and S.G. Davies, TetrahedronLett.. 1985.
2,
2129,
22.
H. Bestianand H. Jensen,Ger. Pat., 1970, 1 807, 498.
23. 24.
D.F. S&river. 'TheManipulationof Air-SensitiveCompounds',McGraw-Hill,New York, 1969.
25.
J.R. Carruthers,and D.J. Watkln. Acta. Crystallogr.Sect. A., 1979,35, 698.
26.
J.R. Curruthers.and D.J. Watkin. "CRYSTALSUser Guide", Issue 9, ChemicalCrystallography Laboratory,Universityof Oxford, 1985.
27.
A.C.T. North, D.C. Phillips,and F.S. Mathews,Acta. Crystallogr.Sect. A., 1968,24,
"International Tables for X-ray Crystallography". Volume IV, pgs. 99-101. Press, Birmingham,England,1974.
149-150,
351.
Kynoch
Terrahedron Vol 42. No. IR. pp. 5123 to 5137. I986 Prmtcd I” Great Rnum
The Asymmetrlc Synthesis of B-Lactams. Stereocontrolled Asymmetric Tandem Michael Additions and Subsequent Alkylations of E-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMe]. X-Ray Crystal Structure of (RS)-E-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMel
Stephen C. Davies,* Isabelle M. Dordor-Hedgecock, Kevin H.Sutton and Jonathan C. Walker, The Dyson Perrins Laboratory, South Parks Road, OXFORD, OX1 39Y,
U.K.
and Richard H. Jones and Keith Prout, Chemical Crystallography Laboratory, 9, Parks Road, OXFORD, OX1 3PD, U.K. (Rewiced
m UK 26 June 1986)
Summary: Michael addition of methyllithium to the E-crotonyl complex (RS)-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMe] followed by trapping of the resultant enolate with methyl iodide gives (RS)-C(n'-C,H,)Fe(CO)(PPh,)COCH(Me)CHMe,l (d.e. > 1OO:l). also generated by treatment of (RS)-[(n'-C,H,)Fe(CO)(PPh,)COCH,CH(OMe),l with three equivalents of methyllithium and methyl iodide. Addition of fl-butyllithium to the (RS)-E-crotonyl complex followed by protonation with methanol occurs with high diastereoselectivity. Quenching with methyl iodide gives (RS)-C(n'-C,H,)Fe(CO)(PPh,)COCH(Me)CH(Me)E-Bul, also generated by treating either diastereoisomer of [(n'-C,H,)Fe(CO)(PPh,)COCH,CH(Me)OMel with two equivalents of c-butyllithium and methyl iodide. Decomplexation gives the known erythro-2,3-dimethylheptanolc acid. Similarly, Michael addition of lithium benzylamide and electrophilic quenching with methanol or methyl iodide occurs with high diastereoselectivlty and gives upon decomplexation, q-methyl- and cis-3,4-dimethyl-N-benzyl-B-lactams respectively. The stereochemical results are rationallsed by addition occurring to the E-crotonyl complex in the anti (C-O to CO) and cisoid conformation and subsequent alkylation of the unhindered face of the E-enolate generated. Confirmation is provided by an X-ray crystal structure analysis of When repeated with the optically pure (RS)-E-[(n'-C,H,)Fe(CO)(PPh,)COCH-CHMel. (S)-E-crotonyl complex, decomplexation gives essentially optically pure (2R),(3R)-c-)-Nbenzyl-2,3_dimethylheptanamide, (4S)-(-)-4-methyl- and (3R),(4S)-(-)-cis-3,4-dimethyl-Nbenzyl-B-lactams. Introduction: The chiral auxiliary C(n'-C,H,)Fe(CO)(PPh,)lt exerts powerful stereochemical control during the reactions of attached acyl ligands.'*'
For example, the Z-crotonyl iron complex 1 is
deprotonated in the cisoid conformation by n-butyllithium to the dienolate 2 which undergoes highly stereoselective a-methylation from the unhindered face generating 3 as a single diastereoisomer.'*'.
2
We describe here in detail the highly stereoselective tandem Michael additions to and subsequent electrophilic quenching of the racemic E-crotonyl iron complex j! which result in the stereocontrolled synthesis of o- and g-substituted iron acyl complexes.
t
Part of this work has been
Unless otherwise stated all complexes are racemic but only those with the R configuration at iron are drawn for clarity. 5123
S. G. Dnvw, et al.
5124 the subject
of a preliminary
independently
and similar
communication’
by Liebeskind
reactivity
We then go on to report
et.al.”
was subsequently
reported
such tandem reactions
of
and lithium benzylamide to the enantlomerlcally pure (S)-E-crotonyl complex -4 which -n-butyllithium upon decomplexatlon give essentially optically pure o,6-disubatltuted carbonyl compounds and I(-mono- and 3,4-disubstituted The possibility additions
of
6-lactams
carbanlons
to a.B-unsaturated
enolate
thus formed has been recognlsed
part
the a,t3-unsaturated
of
particular, system,
where part
moderate
6-centres.“’ achieved Results
respectively,
all
of the tandem stereocontrolled
carbonyl
or all
of
known absolute of two chlral
In general
some time.
has proved
acyclic
cases i.e.
of
the use of a chiral
moiety
of
the
auxiliary
approach.6*7*’
is contained
in the formation
however,
via Michael
alkylatlon
the more successful
carbonyl
can be achieved
addition,
configuration. centres
compounds and subsequent
the a,E-unsaturated
For the corresponding Michael
for
equivalent
to good stereocontrol
in the initial
carbonyl
of
formation
in a ring
both the o-
good stereocontrol
as In
and
has only
been
at the 6-centre.6*a*9
and Discussion:
Several
methods for
recently.‘*“*” methoxide
the synthesis
The most efficient from the 6-methoxy
complex -5 via aldol a readily
generates
acyl
of the E-crotonyl synthesis
complexes
involves
complex 2 have been described
5 and 1 which are derived
reactions
with acetaldehyde
separable
15:l
mixture
iron
the sodium hydride-promoted
and subsequent
0-methylation.”
the E- and Z-crotonyl
of
elimination
from the parent
of
acetyl
This route
complexes
2 and 1
respectively.
4. NoH /Ma1
NaH \
+
I5 : I
Addition at -78’C
of methyllithlum
generated
300 MHz ‘H n.m.r. established
the a,B-dimethyl
from the chemical a Michael
by the methyl intermediate addition
iodide. enolate
in the clsold
butanoyl
shift
(60.91)
The formation addition Since
by methyl
with
of
the a-methyl
doublet
of 2 as the exclusive
thus generating
This
the iron
i.
(d.e.
to the a-centre
indicates
an enolate
>lOO:l
by
were of the
that 4 is
which is
from the unhindered
is consistent
E-enolate
complex 4 in THF
which is characteristic
product
to generate
must have occurred
iron
dlastereoisomer
of
must have the E-conflguratlon. conformation
to the E-crotonyl
conflguratlons
the methyllithium
a-methylatlon
iodide
complex 2 as a single
The relative
spectroscopy).
RS.SR-diastereoisomer.” undergoing
followed
then trapped
face’,
with 2 undergoing
the a Michael
The asymmetric synthesisof B_lactam8
in Oommonwith
anti to the co
ligand
preference
5 to adopt
the
ror
CO llgand
all
other
then molecular a aisoid
would d88tabili8e
iron
models
These prediction8 bond length8
in Tab18 2.
the corresponding
anti
to the
between
CO llgand
were
VeFifi8d
by an X-ray
around
(Figure
the
2).
are iron
the blockfng
effect
given oentre
The E-crotonyl
the C-O and the C-C bonds being
illustrates
Selected
bond lengths
F8(1
)-PC1
Fe(1
I-Ccl
Fe(1
)-C(5)
cc1 )-Of1 Cfl
f 1 )
for
Huckel
of
the
39’.
ti),
Crystal in Table
StW3.UrS
and
la
or f
(Figure
Coordinate8
claold
with
I). are
oxygen
the torsional
down the Fe-P axis
listed is angle and
llgand.
and torsional
angles
f’)
wfth
e.S.d.8
in
fRS)-E-j:(n’-C,H,)Fe(CO)(PPh,)COCH-CHHcl].
2.195(l)
Fe(l)-C(l)-C(2)
1.958(3)
C(1 )-C(2)-C(3)
121.?(4)
1.738(3)
C(2)-C(3bC(4)
125.8(5)
1.223(4)
Fe(l)-P(l)-C(11)
116.1(1)
1.484(6)
C(l)-Fe(l)-P(l)-C(11)
118.9(3)
I-Cfl
)-O(t)
-161 -30
C(l)-C(2)-C(3)-C(4)
)
171
95.2(2)
C(5)-Fell)-C(l)-C(2)
18
69.2(l)
C(3)-C(2)-Cfl
39
Fe( 1 )-Pt
PC1 f-Fe(t
)-C(5)
91.8(l)
Fe(1
)-O(l)
122.9(3)
I-C(1
a clear
$-hFdrOg8n
l*
C(3)-C(4)
)-P(i
the
and the acyl
3 shows a projection
C(S)-Fe’e(t
f-~8(t
atomic
to octahedral
conformation
1.316(6)
c(i
SrtSlySiS
1 and final
18 close
C(2)-C(3)
)-C(5)
between
1.488(S)
)-C(2)
C( 1 I-Fell
oxygen remain8
indicate
TRANSOID
Figure
f”)
the acyl
oonformation.
trlphenylphosphfne
angles
that
calculations’4
interaUtiOn8
transoid
Table
parentheses
type, ‘*
this
It
and bond angles
The geometry
of
Bt8rlC
coniormation.
clsolo
Selected
acyla
and extended
5125
)-O(l) 1 )-C(
11 f-C<
16)
-66
l The atomic coordinates iOr thi8 work are available on request from the Director of the Cambridge Crystrallographio Data Centre, University Chemloal Laboratory, Lensfield Road, Cambridge, CB2 1EB (Oreat Britain). Any request should be accompanied by the full literature citation for this papar.
5126
S. G. DAVIESet cd.
Figure 1.
Figure 2.
Figure 3.
5127
Table 2. Atomic Coordinates sad Equivalent Isotropic Temperature Factors I~IIIIPII~CI~II~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Atom -W(l) P(l) C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) CflO) Cfll) Cf12) C(13) C(14) Cf15) C(M) Cf17) CflR) Cf19) C(20) Cf21) Cf22) Cf23) Cf24) Cf25) Cf26) Cf27) C(2R) O(1) O(2) A(1) A(2) H(3) A(4) A(5) A(6) H(7) A(8) R(9) AflO) A(111 Hf12) Af13) H(14) II Hfl6) Hf17) A(181 A(191 Bf20) A(211 Iif Rf231 A(241 Rf25)
y/b
_-0.17634(31 0.30198(4) 0.1725(2) O.lOE5f3) 0.1287(3) 0.0741(4) 0.1209(2) 0.1301(2) 0.0743(2) 0.1228(3) 0.2078(31 0.2123(2) 0.3195(2) 0.3802(21 0.3889(31 0.3383(3) 0.2779(3) 0.2676(21 0.3980(21 0.4650(2) 0.5360(2) 0.5405(2) 0.4736(2) 0.4018(2) 0.3231(2) 0.3824(2) 0.3981(2) 0.3556(3) 0.2957(3) 0.2792(2) 0.2214(2) 0.0833(2) 0.0469(j) 0.1994(31 0.0607(41 0.003201 0.0972(4.) 0.1167(2) 0.0118(2) 0.0970(3) 0.2595(3) 0.2592(2) 0.4209(2) 0.4330(3) 0.3348(3) 0.2332(3) 0.2259(2) 0.4602(2) 0.5820(2) 0.5943(21 0.4741(21 0.3523(2) 0.4147(2) 0.4406(21 0.3762(5) 0.2705(3) 0.2395(21
0.14239(2) 0.13633(3) 0.0389(2) 0.0014(2) -0.0574(2) -0.0935(3) 0.1502(2) 0.1357(2) 0.1787(2) 0.2372(2) 0.2299(2) 0.166512) 0.0579(l) 0.0062(2) -0.0519(2) -0.0589(2) -0.OOElf2) 0.0499(2) 0.1379(l) 0.1862(2) 0.1850(Z) 0.1362(2) O.OE87(21 O.OE92f2) 0.2073(l) 0.1985(2) 0.2526t2) 0.3158(2) 0.3252(2) 0.2707(2) 0.0034(l) 0.1601(2) 0.0301(2) -0.0732(2) -0.1344(3) -0.0704(3) -0.oe94f3) 0.0392(2) o.l6e7(2) 0.2779(21 0.2602(21 0.1491(2) O.Q151(2) -O.OS53(2) -0.1046(2) -0.0164(2) O.OE51(2) 0.2229(2) 0.2185(2) 0.1315(2) O.O526(2) 0.0571(2) 0.1570(2) 0.2503(2) 0.3583(2) 0.3680(21 0.2785(2)
SIC
__-
U(iso) or lJ(eqnir) -________-_--__--
0.11773(4) 0.26907(E) 0.1115(4) 0.2063(41 0.2689(5) 0.4046(6) 0.2943(41 -0.1376(41 -0.0533(41 0.0125(4) -0.0304(4) -0.1230(4) 0.4034(3) 0.3794(5) 0.4857(6) 0.6139(5) 0.6399(4) 0.5335(4) 0.1515(3) 0.1844(4) 0.0908(4) -0.0349(4) -0.0704fO 0.02150) 0.4239(3) 0.5638(4) 0.6779(4) 0.6554(5) 0.5184(51 0.4040(4) 0.0348(31 0.4ocot3) 0.2234(4) 0.2775(5) 0.3726(6) 0.3734(61 0.5172t6) -0.1893(4) -0.0455(4) 0.0630(4) -0.00380) -0.1523(41 0.3053(5) 0.4592(6) 0.6617(53 0.7222(4) 0.5424(43 0.2672(4) 0.1159(41 -o.oe34(4) -0.1490(4) -0.0018(4) 0.57ROf4) 0.7657(4) 0.7183(5) 0.4950(5) 0.3145(4)
0.0337 0.0295 0.0419 0.0545 0.0638 o.oe5g 0.0435 0.0519 0.0556 0.0539 0.0542 0.0520 0.0335 0.0526 0.0627 0.0579 0.0502 0.0425 0.0345 0.0431 0.0517 0.0517 0.0497 0.0432 0.0348 0.0433 0.05OE 0.0548 0.0565 0.0470 0.0567 0.0636 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0:045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045 0.045
The E-crotonyl iron complex I! reacted with n-butyllithium to generate the enolate E
which on
addition of methyl iodide gave essentially a single dlastereoisomer of the o,g-dimethylheptanoyl oomplex 11; (d-e. >lOO:l:l:l as determined by 300 l4Rz *H n.m.r. spectroscopy).
The relative
configuration ln -11 of the lron-centre to the a-chiral centre was established as RS,SR from the chemical shift (60.98) of the o-methyl doublet" and indicated that as before Michael addition had occurred to 2 In the ciaoid conformation.
The relative configuration of the g-centre was assigned
on the assumption that the i-butyllithium had attacked 2 in the oiaoid conformation. with the COIIfigWatiOm Of fl carbonyl oxygen8 m, from the unhindered iaae. In this way the relatiVe were
astQgned
aa
RSS,SRR and this was confirmed by oxidatlve decomplexatlon to the known,zY!!?!X
5128
S. G. Dams
carboxyllc
acid.*a
dlastereolsomer
et al.
Protonation
of enolate -10 with methanol gave complex -13 as a single as RS,SR by analogy with the formation of RSS,SRR-12. -
assigned
bn no
’ 7))/ 0
The extension precursors studied
of
this
of
this
B-lactams,
’
methodology l
type of reaction.
which on protonation
to the formation
* I ’ has been communicated Thus, addition
gave the g-amlnoacyl
of
complex
Decomplexation
of racemic
by Llebeskind
lithium
g-amino et.al.’
benxylamide
acyl
: Bu
iI
complexes,
We have independently
to 2 generated
enolate
1’(
(RR,SS)-
-15 as a single diastereoisomer. 16.“*” Trapping enolate Ift with methyl -
of -15 gave the known u-methyl-8-lactam gave (RSR,SRS)-17 as a single diastereolsomer. The relative conriguratlons in complexes or -17 were assigned by analogy with complexes -13 and -11. Confirmation was provided by the appearance of the a-methyl doublet for -17 at 61.12 in the ‘H n.m.r. spectrum and by oxldative iodide
-15
decomplexation
of -17 to give the known -cls-3,4-dlmethyl-g-lactam 18.” Epimerlsatlon of -18 by with base gave a 1:2 mixture of -18 and its trans-epimer, Yw thus demonstrating that the
treatment -cls-B-lactam
1s the thermodynamically
less
m
stable
dlastereoisomer. co
m
!? We
shown previously
have
non-nucleophilic E-crotonyl
iron
base,
that
treatment
sodium hydride,
complex i.‘”
the enolate -10. which is then trapped
of the B-methoxy acyl
complexes
in the elimination
of methanol
results
Treatment
of either
generated
Presumably
the first
situ
by Michael
addition
Subsequent
addition
of methyl
iodide
2 or 1 with equivalent
of
gave -11 again
two equivalents
promotes
the second as a single
5 and 1 with the
elimination
equivalent
and generates to generate
of n-butyllithium.
diastereoiscmer.
the
of ;-butyllithium 4 in --
The asymmetric synthesis of /Mactams
5129
I
p-Buli
Similarly, methylllthium
treatment followed
of the 8-dimethoxy
by addition
The formation enolate
acyl
or methyl
of 2 from -19 is consistent 8 which is then qethylated.
complex ‘* -19 with three equivalents of yielded complex 2 as a single diastereoisomer.
iodide
with two sequential
elimination-Michael
Mdi
additions
giving
c
I
Mdi
9
In order efficient
to extend
decomplexation
the highly
diastereoselective
methods described
tandem Michael
to the asymmetric
carbonyl
compounds and I(-alkyl-
and 3,4-dialkyl-substituted
repeated
using
pure acyl
enantfomsrically
C(n’-C.H.)Pe(CO)(PPh,)l. coniiguration acetaldehyde.
The essentially
S-msthoxy
by methyl
iodide.
f[alfi*
l
228.0’
Thus, the optically
we have unambiguously
resulting
complexes
complexes
1:l mixture
fS)-2
and-1
g-laotams,
containing
was treated
of B-hydroxy
treated
the above reactions
complexes
whose absolute
with ;-butylllthium
were 0-msthylated
with two equivalents
were
auxiliary
complex 2,
successively
and
oi a,B-dialkyl-substituted
the chiral
pure (Sl-(*I-acetyl
assigned,”
addition-alkylations
synthesis
and
and the
of n-butyllithlum
(c 0.29,
been deduced previously.
C,H,l)
(d.e.
Oxidative
> 1CO:l:l:l) decomplexation
whose relative of
complex -11 configuration was that
followed
Work-up gave the (S),f2Rl,(3R)-(+)-2.3-dimethylheptanoyl
(S1.(2R),(3R)-(+)-
-11 with bromine
as had in
S. G. D~nps ef al.
5130 dichloromethane
at -78’C
dimethylheptanamide
(Calfi
diastereoisomerically decomplexatlon agreement
purity
Similarly, puriflcatlon, lactam fi stable
of
isomer
Cc 0.69,
could
Finally, conversion
of
(S)-6.7 --
purity
to confirm to complexes
neither
configuration
-20 was
the
at the a-centre
(2R),(3Rl-(-I-
that
complex
as stated.
and then methyl diastereoisomer.
(3R),(U)-(-1-18,
that
(Sl-17 -
iodide
to
Without
the starting
(S),(2R),(3R)-(*)-ll
of
not previously
the (S)-E-crotonyl -
ii. MeCW
(Sl-(+I-acetyl
and (Sl-lJ,
known in optically configuration
as stated.
complex 5 in the
complexes
(S)-&l
were
iii.NaHIMd
lSl,l2Rl,(3R)-W~
2 PhEHZNHli ii. MeI
PhCl$NNH2
% ‘I
more
must accompany
was formed with high diastereo-
than 1OO:l and the absolute
the intermediacy
in
-20 must have
at the a- nor B-centres
epimerisation
the derived
of greater
i.
that
that
to the (3Rl,(4Sl-(-1-cis-3,4-dlmethyl-N-benzyl-6As no trace of the thermodynamically
cs,-g.l.
ii. MeOH
stereochemistry
benzylamide as a single
confirmed
in 421 yield.
i. +di
i.FltCH3NHLi
of
follows
This when combined with the fact
necessitates
has an optical in order
with bromine
pure and that
(>lOO:l:l:l)
form,
lithium
complex lJ
CHCl,))
be detected,
reaction.
complex 2 was optically selectivity
of
The amide (2R1,(3Rl-c-l-
and agaln
retention
than 1OO:l and the absolute
was decomplexed
-29.2’
the decomplexation
active
spectroscopy
It therefore
two equivalents
gave (2R),(3R)-(-)-N-banzyl-2,3-
in 81% yield.
with complete
cases.”
(S)-g-amino-a,B-dlmethyl
(S)-17 -
trans
reported
of greater
[Calb’
of benzylamlne
(c 1.23. C,H,))
-5.3'
had occurred
addition
gave the
l
pure by 300 MHz ‘H n.m.r.
procedure
with previously
an optical (S)-tj.1
and in the presence
0
t Ii
N-Ph
The luymmetlic synlhosis of &lactama subjected
to sodium hydride-induced
with recovered benzylamlde
starting
Oxidative
oomplex lJ
during
([a]b’
the deoomplexatlon
the dlastereotoplc
(the
faces
used In oomblnatlon
acyl
auxiliary
carbonyl
many electrophlles
(4S)-t-j-16 -
was obtained
as the sole
product.
must have an optical
purity
of greater
than
tandem addition
faoe)
pure acyl
attached
for
this
reaction
reaotlons
also
the asymetric
B-lactams
to the ohiral
can be used to quenoh the enolate of
these
complexes,
C(n‘-C.H,)Fe(CO)(PPh,)l ligands
of nucleophiles
and
4.
oompounds and 3,4-substituted
the scope
16 no raoemisatlon
Tt~e tuo new bonds are ?ormed -01s onto one of of the original carbon-carbon double bond. When
ooeplex
unhindered
wide range of E-a,g-unsaturated nucleophiles.
C,H,))
the stereocontrolled
iron
with enantlomerloally
the chiral
a,B-substituted
step,
demonstrate
to the E-orotonyl
of
(c 0.44,
configuration.
The above reactions
potential
together
of
1OG:l and the PS absolute electrophiles
143.0’
l
(S).(2S)-(+I-15 gave the (4S)-(-)-4-methyl-N-benzyl-g-lactam [alb’-34.5’ (c 3.0, MeOH)) in 651 yield. Since MeGHI, lit..”
(c 2.1,
is expected
was lsolated
material
decompleratlon
f[a]~‘-38.5°
Complex (S)-2
of methano1.l’
W-6.7 which as an inseparable mixture was treated with lithium -A single observable diastereoisoler of the (S).(2S)-(+)+Iby methanol.
followed
amino-g-methyl
elimination
5131
of high optloal auxiliary
generated
illustrate
synthesis purity.
Since
are avallable’0
by the Michael
the
of
addition
a
and since of
lithium
is extensive.
Exper lmental All
reactions
vacuum line
and purifications
and schlenk
Tetrahydrofuran(THF) distilled
was dried
from calcium
c-Wltylllthium
over
hydride
Unless
Perkln-Elmer
297 instrument.
otherwise
University
X-ray
crystal Cell
having
structure
approximate
Reflections
and reflection
merged to give [I
> 30(I)]
Crystal
4326 unique
Data, P2,,n
electron atomic
U - 2345.8 (established
density positions,
and an extinction shifts
x 0.20
mm. lhe scan range
from 0.9
(R,,g
factors All
from
reflections
measured every
hour
polarlsation
and
Lorentz,
and equivalent
reflections
of which 2842 were considered
to
were
be observed
analysis. monoclinic,
8 - 15.480
least
a OOQIO~overall
2 = 1a.904(4),
for
non-hydrogen
factor.
(Rw 0.046).
atoms),
for
an overall
and for
saale
respective
factor carbon
was terminated
each reflection
i.
space
parameters
on their
The refinement The weight
om-‘,
by Patterson
included
to “ride”
2 - 8.055(l)
A) 7.30
was solved
refinement
were allowed
temperature
o with II 0.038
The structure squares
(anisotropic
hydrogen ata
(2).
u (Ho-Ka = 0.71069
Mgm-‘.
absenoes).
full-matrix
temperature
than 0.1
0.04)
1.00 - 1.22)
Ho-Ka
upon the intensity.
depending
for
by
a orystal
c(u) was calculated
qin-’
to 6.7’
Three standard
factors
Z - 4, D, - 1.37
Final
in the w/20 scan mode for
The data were corrected
transmission
parameter.
were less
vere measured with graphite
x 0.18
wlth time.
frcm systematic
methods.
atoms and were assigned all
monoohaaated
Fl - 480.33, ii’,
were performed
Services.
intensities
reflections
CI,H,,OIPFe,
analyses
Analytical
MHz
were recorded
4
and used in the structure
6 - 95.63(2)‘. group
(relative
Mass spectra
(RS)-E-C(~‘-C.H.)Fe(CO)(PPh,)COCH-Cal
in the range 0 < 0 < 25’.
variation
on a
on Sruker WH300 (300.13
Elemental
operating
was
were used as supplled
as Nu.jol mulls
spectrometers.
Laboratory
standard
pressure.
between 67’C and 70’C.
ether)
in CDCl,,
FD techniques.
and the scan speed varied
were scanned effects”
0.78
using
Dlchlorcaethane
boiling
were recorded
MHz “P)
CAD-4P diffractometer
dimensions
tan 01’
showed no appreolable absorption
of
and dlstllled.
fraction
H in diethyl
spectra
101.26 using
ketyl
were recorded
and the Dyson Perrins
analysis
on an Enraf-Nonius
CO.95 + 0.35
MHz “C,
ZAB 2P instrument
parameters
radtation
infrared spectra
(1.5
atmosphere
were removed under reduced
to that
and methyllithium
N.m.r.
of Manchester
under a nitrogen
solvents
sodium benzophenone
stated,
‘H) and Sruker AM 250 (62.896 the
Nl
and hexane refers
(1.6t4 in hexane)
by Aldrich.
on a V.G. Uicrcmass
were performed
tube teohniques.*8
when
was
S. G. DA-
5132 calculated t,(X)]
from the Chebyshev series
where X - Fo/Fmax4’.
electron
density
Final
and a detailed
were perPormed with Atomic scattering
are listed
Preparation
of
in Table
in Table
failed
1.
Final
to reveal
atomic
procedure
for
by subsequent
(25 ml) at -78’C
according
to give
any systematic Tables,
and removal
chromatography determine
Volume IV.”
described
of alkylllthiums
with electrophiles
equivalents)
of solvent through
on alumina
H, 6.2: cm-’
P, 6.2.
alumina
(C-O)
‘H n.m.r.
i
ether
analysed
6 7.6
COCHMs). 0.53
(3H, d,
(d,
Jpc
(s,
Ph Cpara),
21.6
31.5
- 7.3
(s.
127.9
Me),
17.1
(-78’C;
He).
C. 70.6;
(s.
with 60:80
Elution
4.43
Jl,a
JpH
1.4 Hz, &HI),
(3H. d, Jl,a
2.77
(lH,
J,,2
were purified
upon removal
of
dlastereoisomer.
Jpc
31.4
(s,
Ph Cpara),
(s,
CH), 31.3
“P{‘H)
Hz. CEO). 136.9 127.9 (s.
n.m.r.
(d,
CH,),
(d.
Jpc 9.4 30.0
85.2
0.91
6.8 Hz. Me); 133.5
(s,
(d.
&HI),
n.m.r.
Cl:11 gave
(Found:
6 71.7:
2.80
(1Hs dq.
(3H, d,
“C(‘H)
Jl.2
n.m.r.
(s.
COCH). 26.4
( Found :
with diethyl
c, 71.55:
J,,,
2.91,
(s.
128.0
(d,
2.34
m/z 510 (M’).
C,,H,,FeO,P
‘H n.m.r.
HZ. Ph Cipso),
Hz, Ph Cmeta).
85.2
CH1). 23.1
CH,).
requires
6 7.6 - 7.3 - 0.61
(d,
-m/z 538 (M+).
133.4
(s,
(d.
C,H,).
18.2
(s,
mixture
C, 71.7;
(15H, m. Ph),
H, 6.75: 4.42
(7H. m. CH(CH,),). 0.47 n.m.r.
JPC 9.5 Hx. Ph Cortho)t
72.7 Me).
(d, 14.3
JpC 4.4 (s.
(5H, d. 0.97 (3H, de 6 221.2 129.4
Hx. COCH). 32.4
Be).
11.8
(se Me);
H, 6.9;
JPC 42.9
(s,
6.6 Hx. Cme):
HZ, Ph Cipso). (s,
- 7.3
(15H. m, Ph),
JAB 16.6 Hz, COCH,), 1.70
(3H, d, J,.,
CH,) 23.0
6 7.6
‘H n.m.r.
(C-O);
(2H, ABX system. 0.41
13
gave complex -13 (821) as a >180:1 mixture Of diastereoisomers. C,,H,,FeO,P requires C. 71.4; H, 6.55: P, 5.75%); vmax P, 5.8.
Jpc 9.3 Hz, Ph Cmeta) 85.3
CH), 29.3
129.5 CHMe,),
ether
1620 s cm-’
7.0 Hz, CH&).
CEO), 136.7
6 221.2
6 71.8:
1905 vs (CEO), C.H,),
Jt,s
7.3 Hz,
complex 11 (93%) as a 160:1:<1:<1
P, 5.5.
(C-O);
(s,
C. 70.7;
JPC 9.4 Hx, Ph Cortho),
72.4
7.3 Hz. 3.0 Hz, COCH), 1.26
-m/z 552 (M+). (RS/SR)-C(n’-C,H,)Fe(CO)(PPh,)COCH,CH(Me)n-Bul Elution
to
fi.
H, 6.8:
JpC 42.3
(s,
solvents
vmax 1900 vs (CEO), 1612 s
7.4 Hz, CONMe major diastereoisomer), 0.82 (3H, t, J,,2 6.9 Hz, CH&), 6.9 Hz, COCHMe minor diastereolsomer); ‘“C(‘H) (3H. d. J,,, -
J,,,
by
hexane (-3O’C).
from
6.8 Hz, CHHH), 0.23
(d.
(s,
Warming to room
(5H, d. JPH 1.3 Hx, C.Hs),
(3H, d, J,,,
ether
C, 72.0: dq.
of
was added
2h).
6.8 Hz, 2.8 Hz. Cyea),
“P(‘H)
vmax 1908 vs (CEO), 1598 s cm-’
P. 5.63);
the addition
with dichloromethane
complexes
P, 6.1s);
HZ, Ph Cipe,c)r
Me);
petrol-diethyl ( Found :
(-78’C;
as a single
(RSS/SRR)-C(n’-C,H.)Fe(CO)(PPh,)COCH(He)CH(Me)~-Bu~ of diastereolsomers.
2h for
spectroscopy
needles
H, 6.1;
(15H, m, Ph),
JpC 42.1
10.8
11 and 13 500 me, 1.04 mmOl) in THF
(2 equivalents)
The product
by ‘H n.m.r.
JpC 9.3 Hx, Ph Cmeta),
(d,
(s,
(d,
9,
which was extracted
as orange
6.9 HZ, Me), 0.33
Jl,z
in
2.
(1H. dseptets.
HZ, CZO). 136.9
oil
gave complex 2 (60s)
requires
7.2 Hz. 2.8 Hz, COCH). 1.41
bond lengths
previously.‘o
complexes
stirring
(Grade V).
and obtained
C,,H,IFeO,P
Selected
to E-C(n*-C.H,)Fe(CO)(PPh,)COCH-CHMel
to give
After
(RS/SR)-[(n’-C,H,)Fe(CO)(PPh,)COCH(Me)CHMe,l with dlethyl
calculations
with e.s.d.‘s
was added to complex 4 (typically
gave an orange
(Grade I),
diastereoselectivites
Elution
All
4.
a dark red solution.
(3 x 10 ml) and filtered
+ 95.21 residual
VAX 111750 COmpUter.”
coordinates
and -40°C; 2h for methylllthlum), the electrophile -n-butyllithium dropwise to the solution at -78’~ and the mixture further stirred temperature
t,(X)
errors.
Crystallography
positional
to the procedure
addition
reaction
(1.2
+ 579.68
showed no significant
1.
the Michael
The alkylllthlum
t,(X)
synthesis
on the Chemical
E-[(n’-C,H,)Fe(CO)(PPh,)COCH-CHMel
Complex ‘( was prepared
4 followed
analysis
1435.25
l
Fourier
were taken from International
are given
parentheses
General
u - C955.87 t,(X) difference
the CRYSTALSpackage
factors
and bond angles
et al.
CH,),
133.4
(s,
C,H.),
19.7
(s,
(d.
“CilH)
- 0.89 n.m.r.
6 220.8
JpC 9.5 Hx, Ph Cortho),
74.1 Me),
(d, 14.1
JpC 4.8 (s.
Me);
4.40
(5H, d,
JPH 1.1 Hx,
(7H. m, CH(CH,),), (d.
129.6
(s.
nZ. COCH,), 36.8 “PI’H)
n.m.r.
0.86
JpC 31.4
(3H, t. Hz.
Ph Cpara). (s.
CHz), 29.3
6 72.4;
5133
The asymmetric synthesis of fi-lactams
Oxldatlve
deccoglexation
of
erythro-2,3-dimathylheptanoic
Bromine (0.1
ml,
12
acid
1.9 lmol)
in THF (2 ml) uaa added dropwise
complex -11 (566 mg, 1.03 mmol) in THF (10 ml) containing After stirring (O’C; 3h). a saturated Na,S,O, solution. Upon further
rewved.
was extracted
addition
with diethyl
of water
(20 ml) and washed successively extracts pale
dlethyl
ether
1.47-0.82
NaHCO, (aq)
(20 ml) and dried
‘H n.m.r.
0.87
(CH),
32.9
1.11
(3H, t, (CH,),
acid
6 2.35
J,,,
(3H, d,
JIIt
29.2
(CH,),
22.8
17.1
n.m.r.
(Me).
(Me).
The
gave a
upon elutlon
vmax (CHCl,)
he
(3 x 15 ml).
Removal of solvent
with
3500 br (0-H).
1.75
(lH,
m, C$He)CH,),
(3H, d,
J1,.
6.8 Hz,
6 181.6
14.0
solution
(2 x 20 ml).
ether
to give
6.7 Hz, Cl$O,H).
“C(‘Hl
(CH,),
Na,SO,).
_ Hz, CH(He)CO,H), 0.92
7.1
6.9 Hz, CH,Cli,);
Jl,,
of
was concentrated
with dlethyl
12 (44 mg, 271).1’
quintet,
(lH,
the aquwus
(20 ml) and then water
(60H-Merck)
gel
solution
a dark brown
(1 ml) was added and the THF
(pH 1).
green solution
(anhydrous
on silica
(O’C)
ml) to give
solution
(pH 1) and extracted
erythro-2.3-dlmethylheptanolc
(6H, m, (CH,),).
CH(Me)CH,), 35.8
with saturated
were reacidified
011 which was chromatographed
1700 vs cm-1 (C-0);
(aq)
to a cooled
(0.4
(15 ml) and acidification The resultant
were uashed with water
yellow
water
(3 x 20 ml).
ether
combined aqueous washings
11 to
(R99/SRR)-C(~‘-C.H.)Fe(CO)(PPh.)COCH(~)Cn(~e)n-WIl
(CO,H),
13.6
44.5
Me);
(CHCO,H),
m/z
(CI/NH,)
176
(n+ + 18). Oeneral
procedure
for
the Michael
addition
E-[(~‘-C.H.)~(CO)(PPh.)COCH-C~) complexes
n-Butylllthlum to give
(0.4
ml. 0.64
an intense
and added dropwise
red solution. mixture orange
lithium
benzylamlde
by subsequent
to
reaction
with electrophiles
to give
15 and 17
at -2O’C -78’C
of
4 followed
After
further solid
complexes
stirring
stirred
(-78’C;
(-78’C;
were purified
solution.
The solution
to complex 2 (250 mg, 0.52 2h),
lh).
which was dissolved
upon removal
mmol) was added to benzylamine
purple
the electrophlle
in dlchlorcmethane
to determine
mmol) in THF (20 ml)
(-2O’C;
cooled
lh),
to
rmool) in THF (30 ml) at -78*C to give (4 equivalents)
Warming to roo11 temperature
by chromatography
of solvents
(70 mg, 0.66
was stirred
on alumina
through
(Orade I),
diastereoselectlvities
was added and the
and removal
and filtered
a deep
of solvent
Celite.
analysed
by ‘H n.m.r.
and obtained
gave an
The product spectroscopy
as orange needles
Lola
dlchlorcmethane-hexane. (RR/SS)-[(~‘-C,H.)Fe(CO)(PPh,)COCH,CH(ne)NHCH,Phl Elutlon
with dlchloromethane-ethyl
dlaatereolscmer.
(Found:
H, 5.8;
P, 5.31);
6 7.6
N. 2.4; -7.2
C&Ph). 6.1
3.08,
2.68
Hz, Me);
42.6
“CIIHl
128.1
C, 71.6:
H, 5.8;
vmax 3300 w,br
4.40
(5H. d,
(2H, ABX system, n.m.r.
Hz, Ph Cipso)t
Cortho), 5.4
(20H, m, Ph),
133.4
6 220.5 (d,
(de JPC 8.5
Hz, COCH,). 51.3
(s,
(10:9:1)
N, 2.4; (N-H),
Jm
18.3
(d,
JPC 31.4
JpC 9.4
1910 vs (CEO). 1600 s cm-’
(s.
3.69,
Hz. CIO),
Hz, Ph Cortho),
49.7
complex -15 (9@) as a single requires C, 71.55;
C,,H,,FeNO,P 3.56
Hz, COCH,). 2.64
126.6
gave
P, 5.0.
JPH 1.1 Hz, C,H,),
HZ. Ph C,ta)r
gHIPh),
fi.
acetate-methanol
(9,
(lH,
141.1
129.7
(s,
(s,
Me);
Jm 12.9 (3H, d,
CH,Ph Cipso).
Ph Cpara)r
CHzPh Cpera)r
gHMe), 20.0
m, CI$ee). 0.68 (a,
85.4
128.2
(6,
“P(‘Hl
‘H n.m.r.
(C-0) ;
(2H, AB system,
136.5 (s,
CIH,),
n.m.r.
Hz,
J,,, (d,
JpC
CH,Ph
73.2
(d,
6 72.2;
JPC
-m/z 587
@I+). (RSR/SRS)-C(II’-C,H,)Fe(CO)(PPh,)COCH(ne)CH(Me)NHCH,PhJ Elutlcn
with dichloromethane-ethyl
dlastereolsooer.
(Found:
H, 6.0;
P, 5.151):
6 7.5
N, 2.3; -7.2
CbPh), JIIl
2.68
6.4
136.4
(2OH. m, Ph),
(d,
JpC 42.6
JPC 9.1
(s.
cH(Me)N),
(8,
H, 6.0;
N, 2.4;
vmax 3330 w (N-H),
4-44
(5H. d,
“C(‘H)
126.1
gH.Ph),
133.2
17.5
P, 5.1.
6 220.7 (d,
1.12
(d,
JpC 9.5
CH,Ph Cpara), (8,
CH@)N).
gave complex -17 (91%) as a single C,,H,,FeNO,P requires C. 71.9;
1910 vs (CEO), 1580 s cm-1 (c-o)8
(1H, m, C$Hee)N),
(s,
-17. (10:9x1)
J pR 1.2 Hz. C,H,),
n.m.r.
Rx, Ph CILIA).
Hz, Ph C,ta), 51.1
C, 71.9;
m. COCH), 1.72
Hz, COCH(gs)):
(d,
601 CM+).
(lH,
acetate-methanol
3.67,
3.32
(3H, d,
JPC 31.5
Jl,,
7.5
85.5
(a, (a,
C.H.),
129.5 71.5
COCH(k));
Jm 13.9
Hz. CHo(e)N),
Hz, CEO), 141.3
Hz. Ph Corthc),
10.0
‘H n.m.r.
(2H. AB system, (a,
(a.
(d. “P(‘Hl
0.54
Hz, (3H. d.
CH,Ph Cipsc).
Ph Cpara),
JpC 5.2 n.m.r.
127.9
Hz. COCH), 51.2 6 70.7;
-m/x
S. G. DAMBPet ul.
5134
General
procedure
for
the oxldatlve
Bromine (2 equivalents) B-amino acyl solution.
complex
(typicrally
After stirring
room temperature. distillation
decomplexatlon
in dichloromethane
500 mg) in dichloromethane
(-78°C;
lh),
triethylamine
Removal of solvent
of
this
which was further
residue
purified
(below
under reduced
glutlon
JAB 15.2
system. 2.1
with aoetone-diethyl Hz, C&Ph),
HZ, JgX cis
(2H. d. (lH, (C-0).
15 Hz, C&Ph).
Jl,a
dd,
2.5
J,,,
136.1
(sHHe),44.4
3.58 3.56
(CH,),
128.7
44.2
18.5
m, CEe).
(Me);
(neat) 15.2
with acetone-diethyl
1740 s cm-’ Hz, C&.Ph),
COC$he)),
3.63
1.16
(5H, m. Ph),
(C-0);
4.52,
3.13
(1H. III. J,,,
He)];
l’Cf*HI
(3H, d,
(lH, JIII
JAB 14.4
6 7.3
(5H. s,
4.9 Hz, 14.5
dd, J1,,
“CI’HJ
(Ph Cortho/C,ta)B
HZ, JgX trans
Ph),
4.65,
4.06
Hz, COCH,). 2.48
n.m.r.
127.6
6 166.8
(Ph Cpara),
oil. -18 (69%) as a colourless (5H, m, Ph), 4.59, 4.04 (2H, AB system,
- 7.2
Hz. CiH(He)N), 3.22
136.2
(Ph Cpara 1, 50.5
(3H, d,
Hz, C&Ph),
7.5 Hz, 6.0 Hz, COCH), 1.11 127.6
[lit.”
gave B-laotam
Hz. 5.4
15.5
(C-O),
the crude B-lactam
(2H. ABX system,
6 Hz. Me)];
128.2
7.6 Hz, COCH(M_a)). 1.07
6 171.2
warmed to
path
47.0
fi.
(1:9)
6.4
J,,,
Short
m/z 175 (H*).
6 7.4
(2H, d, J,,,
n.m.r.
(CH@s)N);
dq,
JI,,
4.00
(Ph Cmeta/Cortho)r 8.8
‘H n.m.r.
(lH,
(3H. d,
ether
2.54
3.05
(*)-cis-3,4-Dimethyl-l-(phenylmethyl)-azetidin-2-one Elution
the
(60H-Merck).
6.1 Hz, he)
(Ph Cmeta/Cortho)r
(CH,).
of
a brown-red
oil. vmax -16 (68%) as a colourless 6 7.3 - 7.2 (5H. m. Ph). 4.60. 4.11 (2H. AB
3.07,
(3H, d, J,,,
Hz, 14.5 Hz, COCH,). 1.17
(Ph Cipso),
green solid.
0.1 mmHg) afforded
gel
‘H n.m.r.
(1H. m, Cfle), (lH,
to give
was added and the mixture
(lOO°C,
on silica
1750 cm-‘I:
4.9 HZ, COCH,), 1.22
(excess)
pressure
to a solution
(15 ml) at -78’C
-16. (1:9) gave B-lactam
ether
1750 s cm-' (C-0) [lit.”
15 and 17 to 8-lactaw
2O’C) gave a tacky
by chromatography
(i)-4-hethyl-l-(phenylmethyl)-azetidin-2-one (neat)
of complexes
(2 ml) was added dropwise
3.51
(lH,
(3H, d, JI,a
(Ph Cipso),
Jl,,
dq,
m, J,,,
J,,,
6.3
7.5 Hz, he).
128.7
(COCH), 47.0
(lH,
7.6
6.4 Hz, CH(W)N) 1.01
43.9
Hz, 5.4 Hz,
[lit”
6 7.23
Hz, 6.0 Hz, C$he)N), (3H. d.
(Ph Cortho/Cmeta),
(CH(He)N),
vmax JAB
J1,,
6.3 Hz,
128.2
(CH,Ph),
13.5
(COCH(&)),
m/z 189 (M+).
Epimerlsation
of
~~~-ois-3,4-Dimethyl-l-~phenylmethyl~-azetidin-2-one
18
The -cis-8-lactam (10 mg, 0.09 mmol) in -18 (80 mg. 0.42 mmol) and potassium tert-butoxide The reaotlon mixture was poured into water (5 ml) tart-butanol (4 ml) were heated (5O’C; 15 h). and extracted
with diethyl
upon evaporation mixture
of -18 and its
system,
JAB 15.2
1.5 Hz, CljCH,). s,
Ph),
(lH,
dq,
4.62,
Hz. C&Ph),
3.15
IH n.m.r. (lH.dq,
(3H, d, J,,,
(2H, AB system,
6.1
Jl,z
(0.6
to give
nvwl)
to revert
removal
of solvent
filtered
through
upon removal spectrum
J,,,
of
gave an orange alumina
solvent
with that
ml, 0.80
diastereoisomer
(5H. III, Ph),
Hz, 2.0 Hz, C&H,),
1.20
(3H.d.
J1,*
3.16
(lH,dq.
6 Hz, CH,),
After
armol).
2.73
4.07
(lH.dq.
(2H, AB J1,,
6.1 Hz, CH,) [lit.” J1,,
1.17
6 HZ
(3H, d.
and
as a I:2 7.4
Hz.
6 7.28
(5H.
, 2 HZ, NCH). 2.74
J,,*
6 Hz, CH,)].
11 from both
(RS/SR)-
and
colour
2.5 h),
(-78’C; further
stirred
(-78’C:
iodide 3h).
with dlchloromethane
diastereoisomer
r#nol) in THF (20 ml) (0.5
ml;
Addition
caused
Warming to room temperature
instantaneously.
which was extracted
methyl
by comparison
and
(2 x 20 ml) and
as an orange or its
powder
‘H n.m.r.
sample.
was repeated
by ‘H n.m.r.
4.61.
Complex -11 (158 mg, 77%) was obtained
(Grade VI.
The product
stirring
and the mixture oil
Na,SO,)
6 and 7
and shown to be single
of an authentic
(anhydrous spectroscopy
mmol) was added to complex 5 (190 mg. 0.37
back to an orange
The above procedure (0.5
ml. 0.96
a dark red solution.
was added in one portion
the solution
- 7.2
JAB 15 HZ, C& Ph), (3H, d,
were dried by ‘H n.m.r.
(RSS/SRR)-[(q’-C.H.)Fe(CO)(PPh,)COCH(ne~CH(Me)n-Bu]
;-Butyllithium 8.03
6 7.4
7.4 HZ, CH,).
(RR/SS)-[(n’-C.H,)Fe(CO)(PPh,)COCH,CH(Ol4e)Fle~
at -78’C
extracts
011 (75 mg, 951) identified
6 Hz, 2 Hz, CHCO). 1.25 oi
The ether
(3 x 4 ml).
trans-eplmer.”
1.27
4.05
J,,,
Preparation
ether
gave a colourless
with complex I(150
mg. 0.29
mmol) and g-butyllithium
oomplex -11 (144 mg, 89%) was again
spectroscopy.
shown to consist
of a single
Preparation
of
(RS/SR)-C(n‘-C.H.)Pe(CO)(PPh,)COCH(~e)C~,l
L:(n‘-C.H,)Fe(CO)(PPh,)COCH.CH(OCk).~ Methyllithium After
The solution,
give
a light
orange
and removal filtered
recoollng
of solvent
through
diethyl
ether
methyl oil
of
(SR)-
stirred
(2.1
and the resulting
which was extracted
ml,
3.1 mmcl) was added
dark red mixture
was added and the solution dlchloromethane
and chrcmatographed
(1:l)
Elutlon
with dlchlorcmethane-methanol
gave starting B-hydroxy
by comparison with sodiw
0.5h).
single
Addition
through yellow
material
complexes of
After
(1O:l)
(SS)-
of methyl
alumina
of
values
through
(1.1
ml,
16.9 mmol),
Concentration
(Grade I).
A single
of
band was eluted
of
solvent
(S)-E-[(n*-C,H,)Fe(CO)(PPh,)COCH-CHt4el
extraction solution
powder (700 mg) identified 2”
of the (1.04
(2O’C;
952) was
stirred 40h) and
(3 x 30 ml) and
on alumina
identified
g,
This mixture
(Grade I)
as a 1:1.4
gave a
mixture
of
spectroscopy.”
C(n‘-C,H,)Fe(CO)(PPh,)(150 mg, 6.3 mmol) and the with dichloromethane
(3 x 10 ml) and
which was chromatographed acetate
by ‘H n.m.r.
and starting
(2R),(3R)-(-)-N-benzyl-2,3-dimethylheptanamlde
Thus (SRI-iand (0.4
sample.
(1:l)
spectroscopy
material&z.
on alumina which upon as a 2:l
This mixture
purification.
(ss)-[(no-C.H,)Fe(CO)(PPh,)COCH,CH(OE(e)nel
iodide
which
4
20
(S),(2R),(3R)-(*)-[:(rl’-C,H,)Fe(CO)(PPh,)COCH(He)CH(~te)~-Bul above.
stirring
with dlchlorcmethane-ethyl
of
of
gave an orange
solution
mixture values.’
1 by ‘H n.m.r.
and (SS)-
(Grade V) gave an orange
removal
Preparation
fiand
(4:l)
mg. 1.67 mm011 and sodium hydride
yellow
further
further
and chromatography
(SRI-
mixture
was used without
with an authentic
with dichloromethane
acetate
ml)
with
THF (30 ml) was added and the reaction
48h). Removal of solvent,
alumina
extraction
diastereolsomerlc
011 which was extracted
ml,
(0.5
with dichloromethane-ethyl
with the literature
with dichloromethane-ethyl
I(855
(2O’C;
Elution
(0.4
methanol
(Grade V) gave an orange
by comparison
(S)-E-[(n’-C.H.)Fe(CO)(PPh.)COCH=CHMe~
stirred
2h),
and (SR)-[(I’-C,H,)Fe(CO)(PPh,)COCH,CH(OH)He]
iodide
(Grade V).
band eluted
of acetaldehyde
(-78’C;
Removal of solvents,
a 1.4:1
gave
(200 mg, 8.3 mmol),
gave an orange
COCH,CH(Ot4e)Me]gand filtration
with as shown
g, 2.2 mrocl) in THP (30 ml) at
(1.0
stirring
(Grade I).
1 identiiled
THF (20 ml) was added to the mixture reaction
dlastereoiscmer
A solution
lh).
further
(SRI- and (ss)-[(n’-C,H,)Fe(CO)(PPh,)COCH,CH(OHe)Mel Preparation
(2 x 20 ml) and
gave upon elutlon
6 and 7 from
(9)-(+)-z”
through alumina
on alumina
the spectroscopic
hydride
of solvents
filtered
dichlcrowtthane
(Grade I)
50%) as a single
(-78’C;
warmed to room temperature.
acetate
corresponding
to
stirred
(3 x 20 ml) and iiltratlon
was concentrated
(20°C,
with
on alumina
to
Warming to rocm temperature
5
7.2 mmcl) in THF (2 ml) was added dropwise.
removal
became dark red in
(2h),
(-78OC; 2h).
complex 2 (124 qg,
of solvent
mmol) in THF
6.42 mmol) was added in one portion
and (~)-C(~g-C.H.)Pe(CO)(PPh.)COCH,CH(One)~l
n-Butyllithium
combined
and stirring
ml,
Chromatography
(Grade VI.
(S)-(+)-[(n’-C.H.)Pe(CO)(PPh.)C~l
identified
(0.4
(255 mg, 0.48
spectroscopy.
Preparation
-78’~
iodide
whioh was further
gave an orange
alumina
and removal
by ‘H n.m.r.
to complex -19 ”
upon warming to -40°C
(-78’C).
solution
9 from
19
(1.3 ml, 2.02 mmol) was added
(20 ml) at -78’C. colour .
5135
asymmstric syllthcsis of j%ctams
The
(W-1
aand
(356 mg, 0.70
cwas
1 by an identical
mpol),
fi-butylllthium
prepared
procedure (1.0
ml, 6.4 mmol) gave (S),(2R),(3R)-(*)-x(317 mg, 81%), Calb’
ml,
from (SRI-
to that
and
described
1.6 mmol) and methyl
+ 228.0' (c, 0.29,
(2 ml) was added dropwiseto a solutionof C,H.). Bromine (0.04ml. 0.78 mmol) in dlchloromethane (S).(2R),(3R)-(+I-=(317 mg. 0.57 mmol) in dichloromethane (15 ml) at -4O’C to give a dark brown solutlon.
After
stirring
(-4O’C;
lh),
benzylamine
(0.13
ml,
1.2 mmol) was added and the mixture
5136
S. G. D~nas et al.
narmed to room temperature. (60H-Herck).
Elution
solid
identified
40:60
petrol-diethyl
The solution
with 40:60
was concentrated
petrol-diethyl
ether
as [(I’-C,H,)Fe(CO)(PPh,)Brl ether
(1:2)
C,,H,,NO
(c~cl,)
(2H. m. C&Ph). Jltl
requires
3450 m (N-H), 7.0
2.02
Preparation
of
of solvent
Thus, (1.4
[albc
as a single
to that
of
2.75
mixture
described
benzylamide
mm011 to give
0.89
for
0.69,
(106 me, 65%).
(S)-?
generated
Oxidative
described
and (SR)-5
identified
(1.5
1.23.
C,H,);
5.72
vmax
(lH,
br,
NH), 4.45
1.14
7.0 Hz, CH&s);
of lithium
from benzylamine
iodide
(0.4
(3H, d.
e
benzylamide
(0.35
ml,
following
3.2 mm011 and
(c 2.1.
(SR)-5
x
the general
and
(153 mg,
procedure
-18 (20 mg, 4211, synthesised above.
16 lithium
benzylamide
2.4 mmol),
ml,
with an authentic
generated
from benzylamlne
and methanol
(0.6
previously.
Work-up gave
12 (690 mg. 81%).
described
to oomplex if
ml, 6.4 mmol) was added to
(700 mg) obtained
by oomparison
-16 synthesised
Acknowledgements:
with
18
deccmplexation
above,
- (W-1
procedure
Cala’ -38.5’
to (i)-
(c,
J,,,
Elution
H, 10.4;
(S)-[(n’-C,H,)Fe(CO)(PPh,)COCH04e)CH(HelNHCH,Ph~
mmol) and ;-butyllithium
the general
respects
C, 77.5;
(7H, m, CH(CH,),).
(3H, t.
the addition
(4S)-(-)-4-methyl-N-bensyl-6-laotam
of
sample. of
(5H, m, Ph),
(3R),(4S)-(-)-cis-3,4-dimethyl-N-benzyl-B-lactam CHCl,) identical in all respects to (i)-18-
the procedure
C.H.)
following
I.H.D-H,
- 5.3’
6 7.36-7.26
6.7 Hz, CH&),
C(rl”-C,H,)Fe(CO)(PPh,)COCH,CH(He)NHCH,Phl (c 0.44,
[alfj’
(Found:
Hz, COCH), 1.70-1.00
2.24 mrcol). and methyl
diastereoisomer.
c,
Following 2:l
JI,,
7.1
81%).
above gave the
-29.2’
ml,
N, 5.7%;
‘H n.m.r. J,,l
(3H, d,
lithium ml,
(501 qg, 0.98
Preparation (0.3
H. 10.2;
cO(C-0);
quintet,
procedure
was followed.
261)
20 (114 qg,
crystals
gel
gave a green
91 04+-156).
g-butyllithium
described
3
on silica
of solvent
with an authentic
gave white
(3R).(4S)-(-)-ois-3,4-dlmethyl-N-bensyl-B-lactam
An identical
(W-1
(lH,
Hz, CHMM), 0.91
(ACE/NH,) 247 &I+),
C, 77.7;
1660
and removal
by comparison
and removal
(2R),(3R)-(-)-N-benzyl-2,3-dimethylheptanamide N, 5.6.
and chromatographed
(2:l)
[ala1
(S),(2S)-(*I-
143.0’
l
sample.
ml) was added to the
Oxidative
decomplexation
above gave the (4S)-(-)-4-methyl-N-benzyl-6-lactam
HeOH) (lit.,az
[alb’
-34.5’
(c 3.0.
-16
MeOH)) identical
in all
previously.
We thank the SERC for
a studentship
(to
J.C.W.)
and financial
support
(to
K.H.S. and R.H.J.).
References 1.
C.J. Baird and S.G. Davies, S.G.
Davies,
and K. Prout.
S.G.
Davies,
Tetrahedron
J. Chem. Sot.,
and K. Prout.
Tetrahedron
L&t.,
J.L. 2.
Lett.,
J. Chem. Sot.,
H.E. Welker,
Tetrahedron
Brown6 S.G.
L&t.,
1984, 25.
V. Goedken.
J. Am. Chem. Sot. ,1984.
S.G.
Davies
and J.C.
4.
S.G.
Davies,
R.J.C.
Easton,
Lett..
106,
4341
S.L.
L.S.
Baird,
J.A.
K. Broadley
Dordor. S.G.
and P. Warner,
Brown, S.G.
P. Warner,
Davies
P. Warner,
Bandy,
and
and P. Warner,
R.H. Jones,
Davies,
D.F.
and Foster,
623. 194;
Liebeskind,
L.S.
Liebeskind
M.E. Welker,
and and
441.
J. Chem. Sm., K.H. Sutton,
213;
1983, 2.
i
I.H.
Davies,
1986, 2,
Organometallics,
3.
Walker,
1446;
G.J.
1202;
I.M. Dordor-Hedgeoock,
Chem., 1985, 2,
S.L.
Tetrahedron
and H.E. Nelker,
Davies,
S.G. .Daviea,
Chem. Commun., 1965,
Seeman, and P. Warner,
L.S. Liebeskind
4815;
S.G.
1743;
956;
J. Organometal.
1985, 6,
Chem., 1983, 21(8, Cl; Chem. Commun., 1983,
1904. 25,
Chem. Common., 1984,
R.H. Jones, K. Prout,
J. Organometal. J. Chem. Sot.,
Chem. Commun., 1985,
J.C.
Walker,
209.
and R.H. Jones,
submitted
for
publication. 5.
L.S. Liebeskind
6.
J.D.
Morrison
‘Asymmetric
and M.E. Welker,
Vol.
3. 1984,
pp.
252-267.
Tetrahedron
Synthesis’,
I.&t.,
Academic Press,
1985, 26,
3079.
New York,
Vo1.2,
1983,
PP. 201-241
and
Theasymm~tricsynthesis
7.
5137
offl-lactama
K. Tomioka.F. Masumi, T. Yamashlta,and K. Koga, TetrahedronI&t., 1984,25, 333; K. Tomioka,H. Kawasaki. Y. Iltaka.and K. Koga, TetrahedronLett.. 1985.a. K. Tomioka,H. Kawasaki,and K. Koga, TetrahedronL&t.,
1985, 26,
3027;
903;
A.I. kvers
and
B.A. Barner. J. Org. Chem., 1986,51, 120; J. Nokami,T. Ono, and S. Wakabayshi. TetrahedronLett.. 1985,26, 1985; Y. Fukutani.K. Maruka,and H. Ysmamoto,Tetrahedron Lett.. 1984,25, 5911: C. Iwata,K. Hattori,S. Uchida,and T. Imanishi.TetrahedronL&t., 1984,3. 2995; C. Iuata,M. Fujlta,K. Hattorl,and S. Uchida, TetrahedronLett., 1985.26, 2221; O.H. Posner and E. Aslrvatham,J. Org. Chem., 1985,50, 2589: G.H. Posner and M. Hulce, TetrahedronL&t., 1984,5
379; C.H. Posner.T.P. Kogan, and M. Hulce, Tetrahedron
1984,25. 383; G.H. Posner.L.L. Frye, and M. Hulce, Tetrahedron,1984,9, 1401. J. Fujiwara,Y. Fukutani,M. Hasegaua.K. Maruoka,and H. Yamamoto.J. Am. Chem. Sot.. 1984.
e,
a.
106, 5004; S. Hashimoto,N. Komeshima,S. Yamada,and K. Koga, Chem. Pharm. Bull., 1979, 2437; T. Mukalyamaand N. Iuasawa,Chem. Lett., 1981, 913; T. Kogure and E.L. Eliel. J. Org. Chem., 1984,49. 576; P. Mangeney,A. Alexakis,and J.F. Normant,TetrahedronLett.,
3,
1983.3 373; T. Hukaiyama,T. Takeda,and K. Fuimoto. Bull. Chem. Sot. Jpn., 1978,II, 3368; A.I. Meyers, R.K. Smith, and C.E. Whitten,J. Org. Chem.. 1979. 3, 2250; K. Soai, H. Machida,and A. Ookawa.J. Chem. Sot., Chem. Commun.,1985, 469; K. Tomioka.T. Sueuaga,and K. Koga, TetrahedronLett., 1986,3, 9.
369.
W. Oppolzerand H.J. Loher, Helv. Chlm.
Acta..
1981,
&
2808;
W.
Oppolaer,R. Moretti,T.
Godel, A Meunier,and H. Loher, TetrahedronLett., 1983,211,4971; W. Oppolzer,P. Dudfield, T. Stevenson,and T. Godel, Helv. Chim. Acta., 1985, TetrahedronLett.. 1986,3,
1139;
68,
212; W. Oppolzerand T. Stevenson,
G. Helmchenand G. Wegner. TetrahedronL&t., 1985,6,
6051. 10.
S.G. Davies, R.J.C. Easton,J.C. Walker,and P. Warner, J. Organometal.Chem.. 1985,296, c40; S.G. Davies, R.J.C Easton.J.C. Walker,and P. Warner, Tetrahedron,1986,r(2,175.
11.
L.S. Liebeskind,R.W. Fengl, and M.E. Welker, TetrahedronLett., 1985,s
12.
S.G. Davies, I.M. Dordor, J.C. Walker,and P. Warner, TetrahedronLett., 1984,25. 1333.
13.
3075.
S.G. Davies and J.I. Seeman,TetrahedronLett., 1984,25, 1845; S.G. Davies, J.I. Seeman, and I. H. Williams,TetrahedronLett.. 1986,21, 619.
14. 15.
S.G. Davies and J.I. Seeman. unpublishedresults. Y. Yamamotoand K. Maruyama.J. Chem. Sot., Chem. Co-n.,
1984. 904. We thank Professor 2,3-dimethylheptanoic
Yamamotofor providingspectroscopicdata on erythro-and 16. 17.
S.R. Berryhilland M. Rosenblum.J. Org. Chem.. 1980, F.F. Blicke and W.A. Gould, J. Org. Chem., 1958,3,
acid.
'15, 1984.
1102; I. Ojima and H.B. Kuon.
Chem. Lett., 1985, 1327. 18.
P.K. Wong, M. Madhavarao.D.F. Marten,and M. Rosenblum,J. Am. Chem. Sot., 1977,99, 2823.
19.
N. Aktogu,H. Felkin,G.J. Baird, S.G. Davies,and 0. Watts, J. Organometal.Chem., 1984, 262, 49.
20.
S.G. Davies, I.M. Dordor-Hedgecock, K.H. Sutton,J.C. Walker, C. Bourne,R.H. Jones, and K. Prout, J. Chem. Sot., Chem. Comuun.,1986. 607.
21.
R.W. Johnsonand R.G. Pearson,J. Chem. Sot., Chem. C-n.
1970, 986; S.G. Davies,
I.M. Dordor-Hedgecock, and P. Warner, TetrahedronL&t., 1985,26, 2125; P.W. Ambler and S.G. Davies, TetrahedronLett.. 1985.
2,
2129,
22.
H. Bestianand H. Jensen,Ger. Pat., 1970, 1 807, 498.
23. 24.
D.F. S&river. 'TheManipulationof Air-SensitiveCompounds',McGraw-Hill,New York, 1969.
25.
J.R. Carruthers,and D.J. Watkln. Acta. Crystallogr.Sect. A., 1979,35, 698.
26.
J.R. Curruthers.and D.J. Watkin. "CRYSTALSUser Guide", Issue 9, ChemicalCrystallography Laboratory,Universityof Oxford, 1985.
27.
A.C.T. North, D.C. Phillips,and F.S. Mathews,Acta. Crystallogr.Sect. A., 1968,24,
"International Tables for X-ray Crystallography". Volume IV, pgs. 99-101. Press, Birmingham,England,1974.
149-150,
351.
Kynoch