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High-pressure (2+2)cycloaddition of toluene-4-sulphonyl isocyanate to glycals
oob3-m0/85 53.00+ .M Pcrgamoa PIas Ltd.
HIGH-PRESSURE
(2tZ)CYCLOADDITION OF TOLUENE-4-SULPHONYL ISOCYANATE TO GLYCALS
Marek CBMIELEWSKI~ Zbigniew KAKUkA, Czesraw BEKiECKI, Piotr SAZANSKI,
Janus.2
JURCZAK and Halina AD~OWI~§
Institute
Polish Academy of Organic Chemistry, 01-224 Warszava, Poland
of Sciences,
(Received in UK 26 February 1985)
Abstract - High-pressure (2+2)cycloaddition of toluene-4-sulphonyl isocyanate to glycals is examined. Reactions proceed regiospecifically to afford single products in case of all 3-substituted glycals. Upon heating or even after standing at room temperature adducts undergo retro-addition to give starting glycals. Various aspects of the cycloaddition are discussed, especially retro-reaction and rearrangement of B-lactams to a,S-unsaturated amides. Recentlywe
have reported on high-pressure ~2t2)cycloaddition of toluene-4-sulphonyl isocyanate to
glycals 1 - &.l The reaction proceeds regio- and stereospecifically to afford a B-lactam ring in position trans to the acetoxy group at C-3 of the glycal moiety (5 - 8). Owing to the enol ether structure of glycals, cycloaddition offers an approach to various g-lactams, particularly to oxapenams and oxacephams. Owing to the stereospecificity of the reaction, glycals of D-series 1. and 2 lead to S-configuration at the carbon atom
attached to the nitrogen and oxygen atom, whereas glycals of L-series 3 and
i lead to R-configuration at the C-l carbon atom. This offers stereocontrol in formation of an appro priate configuration at the carbon atom crucial for the biological activity of f3-lactam antibiotics. Cycloaddition of tosyl isocyanate to dihydropyran 2 at low temperature ('LOOC)and atmospheric pressure leads to formation of bicyclic f3-lactam-15. Elevation of the temperature of cycloaddition 3 2 causes a rearrangement of the four-membered ring to open-chain amide -21. Recently Barrett et al. have found that 2,2,2-trichloroethylsulphonyl,
2,2,2-trichloroethoxysulphonyl
isocyanate react with dihydropyran 2 to give unsaturated amides 19 - 2.
and trifluoroacetyl
no B-lactam being isolated
in all three cases. Similar results have been reported by Chan and Hall4 for the addition of tosyl isocyanate to dihydropyrans 12 - -14. The 5-substituted dihydropyrans 2
and -11 have, however, been
found to react with trifluoroacetyl isocyanate to give the expected S-lactams 16 and l7, respecti3 vely, obtained after cleavage of the trifluoroacetyl group with silica-gel. Attempts
at adding chlorosulphonyl isocyanate to glucal 1 have failed to give the expected !3-let5
tam; isocyanate acted only as a Lewis acid, causing the known dimerisation of the sugar substrate.
The aim of the present work was to elucidate the stereochemistry of (2+2)cycloaddition of tosyl isocyanate to glycals, as well as to interpret the chemical properties of the bicyclic B-lactams synthetized. Therefore we selected a wide and representative group of glycals. namely 1 - 5 and -22 -3. RESULTS AND DISCUSSION All cycloadditions. except that to 23, were performed in absolute ethyl ether either at room temperature or at SO'C, under 10 - 11 kbar pressure. Cycloaddition to glycals 1. 3. A, 21. 23, 25 and 27_ proceeded with formation of products which crystallized from the post-reaction mixture, vhereas
9 Permanent address: Department of Chemistry, Technical University, Warszawa, Poland 2441
M. CHMIELEWSKI
2442
Chart
er al.
1
/
Ts
AcC) 1: R1=OAc,R2=H
3:
R=H
5:
2: R1=H,R2=OAc
3:
R=CH3
5: R'=H,R'=OAc
R1=OAc,R2=H
7: R=H 8: R=CH3
R’
Q0
bR3
R3
(-$R2
R2
9. Rl,R2,R3,H -. -10: R1=R3=H,R2=CH3
d 12:
R1,R2=R3,CH3
u:
12: R1=R3=H,R2=OCH3
11: R1=R3=H,R2=CH2Ph z:
R1=H.R2=Ts
16: R1=CH3,R2=H
R1=R3=CH3,R2=OCH3
G:
R1=CH2Ph,R2=H
Is: R=Ts -19: R=CC13CH2S02 &I: R=CC13CH20S02 u:
R=COCF3
R’
9 R3
R
N--TS
/
-22: R1=CH20Ac,R2=OAc,
25: R1=R2=H
R3=H -23: R1=CH20Ac,R2=R3=H
a:
R1=H,R2=OAc
-* 24. R1=CH20SiMe2t-Bu,
3:
R1=OAc,R2=H
R2=R3=OSiMe
2
-28: R1=CH20Ac.R2=0Ac, R3=H
-31
-29: R1=CH20Ac,R2=R3=H 30: R1=CH20SiMe2t-Bu, R2=R3=OSiMe t-Bu 2
t-Bu
AGO R&Ts
PhC(q,Ts
PhC($$,fTs Y-2 AcO
d 2:
R1=CH20Ac.R2=0Ac
33: R1=CH20Ac,R2=H
-34
-35: R1=H 2: R1=OAc
CONHTs 37
High-pressure (2 + 2) cycloaddition of tolucne4sulphonyl derived
the products
from galactal
0-Benzylideneglucal Cycloadditions of addition 2.
proceeded
to glycals
both isomeric
regiospecifically.
were obtained
5),
-35 were obtained. determined
from the ‘H NMRspectra
In case
more polar
of
obtained
of cycloaddition
to 2,
g-lactam,
and it
of high-pressure
room temperature
of all
with the respective
Alla1 tained
shift
of
21 did not react
as the unique
The gross (Tables
of
For assignment
between these
be explained mation of (Table
towards
of
xylal.
by cooling
of
materials
after
Raising
separation of the tem-
the reaction
vessel
However, all
amides (5-10X);
the temperature
5).
with a minute amount of
of cycloaddition.
a,&unsaturated
Elevation
the isocyanate
products
we examined the respective rity
followed
were
Table
of solvent.
of starting
from the mother liquor
the yield
g-lactams
Experimental,
to
reaction
one of which (8)
of cycloaddition
was
to 2. cau-
amide 2.
at room temperature,
whereas at 50°C amide -39 was ob-
product.
structure
1 and 2).
the reaction with
also
Ex-
33. 3& -*
of diastereoiso-
evaporation
traces
as 3-N-tosylcarbamoyl
increased
and identified.
(cf.
careful
contained
32. _* 29 _*
of isomeric
isolated
after
low (cf.
28 _I
the mixtures
ratios
1 was contaminated
to 50°C,
by chromatography
sed a significant
materials
by chromatography
were contaminated
to rhamnal 3 the alternative
obtained,
products
was characterized
isolated
4.6-
of an addition
-23 and -25 was relatively
B-lactams
the product
mixtures
syrups.
of s (95%) over
of diastereoisomers
The approximate
as crude
decompression,
in case
2,
at room temperature
experiments
before
as crude
isomer 2, 6, 1 and 30 as a result
predominance
the crystalline
mixtures
were obtained
a single
mixtures
pure components.
compound -37 which was isolated
of crystalline perature
the respective
6 and -30 were characterized
post-reaction
(TLC).
into
(24)
whereas
respectively,
Owing to the instability
not be separated
All
yielding
to 3-deoxyglycals
and therefore
mers could
glucal
2443
conditions.
with substantial
of cycloaddition
Table
Cycloadducts
and silylated under these
l_, 2, 3 and 24,
products
Stereoselectivity
perimental,
(2)
26 was unreactive
isocyanate to glycals
of the l3 C NMRsignals
data of starting
two sets
of spectral
by introduction
the pyranoid
2 - 8 and 28 - -39 was determined glycals
data.
ring,
to appropriate
(Table
The upfield
of a four-membered which were also
ring
from the ‘H and 13C NMRspectra
into
exhibited
3).
carbon
atoms of
There is no, however,
shift
of C-3,
simila-
C-4 and C-5 resonances
the molecule
by the values
Blactams,
direct
and by changes of vicinal
can
in the confor-
coupling
constants
1).
The (2+2)cycloaddition
of
tosyl
isocyanate
to glycals
is
probably
a pseudo-concerted
reaction6
(Scheme 1). Scheme
The presence
of an a-substituent
cedifferentiation respect
to the
addition
glycal
was used.
All
g-lactams
tam ring
2.
is well
5 - g,
l5,
over
28 - 35,
oxymethyl treated
to give
stereospecifically
of
to specify
the diastereofa-
preferentially
trans
by the high stereoselectivity observed
(TLC),
could, one:
although
however,
in all
an excess
resulting
from trans
with
of cyclobe the result
reactions,
the star-
of the isocyanate
lower diastereofacedifferentiation, the adduct
and thus afforapproach
of
the iso-
group.
with methanol
the respective with
helps
enters
the alternative
mixture
23 and -25 exhibited with predominance
ring
expressed
The high stereoslectivity
to the terminal
the four-membered proceeded
This
atom greatly
The isocyanate
in the post-reaction
products,
respect
at C-3.
inglycals.
of one diastereoisomer
3-Deoxyglycals of
at the C-3 carbon bond
1. - 5 and 24.
was detected
with
ning of
group
stability
ded a mixture cyanate
the double
acetoxy
to glycals
of the lower ting
of
1
inversion
at room temperature,
glycosides
-40 - B. of the configuration
undergo a rapid
The opening at the C-l
of
ope-
the g-lac-
carbon
atom.
2444
Table
M. CHMIELEwsKlef a/. 1 H NMR data
1.
for
B-lactams
2 - 2 and 28
- 35
Comp .
H-l
H-2
H-3 H-3’
H-4
H-5
H-6 H-6’
J12
J23
2
5.88
3.55
5.27
4.91
3.67
4.01 4.20
6.2
3.1
6 1
6.03
3.40
a
a
a
a
5.3
5.3
-
a
-
5.84
3.51
5.26
4.90
3.48 3.97
-
6.2
2.7
-
5.9
-
8 28
5.85
3.52
5.22
4.71
3.48
1.12
5.3
2.4
-
5.4
-
7.5
J24=0.9,
5.00
3.35
2.00 2.30
4.87
3.67
4.16
5.5
6.1
2.6
4.2
3.5
3.3
IJ~~+J~~,
22
5.77
3.31
a
a
3.73
3.97 4.05
5.4
4.1
8.5
a
a
b
J56=4.5,
30
5.76
3.24
4.11
3.77
3.52
3.56 3.67
5.8
3.3
-
2.9
-
2.0
J24-;95;
‘34
‘3’4
‘45
-
5.6
-
7.7
J24=1.3, J66,-14.5
5.68
3.91
5.08
4.85
3.74
1.21
4.7
a.4
-
7.4
32
5.57
3.43
a
4.94
3.80
;.y;
4.6
/J23+J23,1
p34+J3,d
4.0
J56=5.3,
=16.7
-9.4
7.5
-33
5.69
3.40
a
a
a
3.83 3.88
5.6
2.0
6.8
a
a
a
-34
5.77
3.32
2.05 2.37
a
a
3.61 4.00
5.4
11.1
7.1
4.8
12.5
a
-35
5.79
3.25
1.86
a
a
4.23
4.8
8.8
6.9
3.7
11.6
a
not resolved
Table
a
2.
or too
13C NMR data
complex for
for
5 - 3,
adducts
J24=l
J56=7.2 [=a.3 J56,=5.8 J56=7.9,
2,
28,
22
37
- 35,
J56,=4.1,
.O
J33,=11.6,
IS
and Is,
(CDc13)
c-1.
80.42
80.29
79.91
80.99
89.48
165.53
80.24
al.19
80.31
80.31
79.78
160.62
C-2
51.78
49.79
51.36
52.47
46.53
108.00
45.63
45.97
48.81
45.22
48.80
103.84
C-3
66.86
65.48
66.42
66.77
23.79
20.65
23.41
21.43
a
23.68
C-4
66.65
62.86
65.37
72.04
18.44
18.60
66.50
16.82
a
73.21
C-5
69.49
68.72
60.72
67.40
57.94
66.50
71.89
67.43
66.59
64.11
a
61.38
C-6
62.71
61.58
-
la.22
-
-
64.26
65.91
65.81
68.58
a
-
not
Table
visible
3.
or
overlaped
13C NMR data
for
by absorptions
glycals
L-
4,
of
2,
a major
22,
23,
a 73.60
J35=2.2
(DM%-d6)
64.48 64.42
isomer
-25 - 21
(CDc13)
C-l
145.71
145.46
148.04
146.00
144.50
142.71
143.38
143.14
145.42
147.35
c-2
99.07
98.92
97.42
98.85
100.60
97.75
100.52
98.66
100.79
98.43
c-3
67.48*
63.81*
67.22
68.33
23.20
25.68
24.27
26.37
68.90*
62.01
c-4
67.28*
63.95*
63.62*
72.55*
19.90
65.69
19.21
75.11
77.01
76.05
c-5
74.04
72.84
63.47*
71.88*
65.80
73.96
72.72
69.97*
68.31*
64.93
C-6
61.40
61.95
-
16.56
62.41
66.23
68.99
68.90
68.60
assignments
may be reversed
-
J56,=6.0,
*
b )J45+J4.51=12.4
analysis;
J56,=6.7,
J24=1 .3
-31
-
J56-4.4,
a ::;
J66’ J56=6.6
a
*
‘23’
J66,=12.1
High-pressure (2 + 2) cycloaddition
of tolucne4sulphonyl
isocyanate to glycals
Chart 2
@e
Aches
ACQMe
42:
40: R1=OAc ,R*=H
R=H
t-BuMezSiO
&ONHT= -46
CONHTs
CONHTs
AGO
CONHTs
~ONHT~
47
Thespectral
data of the glycosides
@
- 49 (Table
4) help
to prove
the configuration
of bicyclic
B-lactams. It is well activation For
known that
volume,
Table Comp.
4.
acceleration
of
‘H NMRdata for
H-l
accelerates
enhances
the rate
of
volume varies
the reaction
reactions
characterized
, whereas it retards
the stereoselectivity
the activation
(2+2)cycloaddition,
significant
high pressure
and greatly
from -30 7
to -50 cm3/mol,
H-3 H-3’
H-4
H-5
H-6 J12 H-6 V
‘23
‘23’
‘34
J45
7.97
-
5.51
5.08
4.49 4.20
-
-
-
-
s
a
-38
7.85
-
5.66
5.23
4.59
4.14 4.35
-
-
-
a
a
39
7.71
-
5.69
3.89
4.36
3.04 4.54
-
-
-
3.4
10.6
-40
4.51
2.80
5.47
4.99
3.74
4.17 4.37
8.3
-
9.1
9.0
41 -42
4.44
2.85
a
a
3.86
a
8.2
10.8
-
a
a
4.12
2.70
5.43
4.97
a
-
7.6
10.0
-
9.5
5.3 9.0
43 -44
4.46
2.75
5.46 4.74
3.61
1.23
8.4
10.6
-
9.0
9.1
4.30
2.52
1.72 4.71 2.32
3.62
4.15 4.23
8.4
13.0
4.3
11.1 5.1
10.0
J s-13.6, J$=12.6
cs
4.25
2.22
a
a
3.61
4.06 4.13
8.6
12.4
4.3
a
2.0 11.5
J56=4.0,
-46
4.80
2.50
a
a
4.02
4.10 4.18
0
C]JI=10.9
a
3.4 11.5
-47
4.42
2.51
1.99 2.25
3.55
3.38
3.75 4.28
8.5
12.2
4.2
11.7 4.5
9.2
48
4.85
2.82
2.15
3.69
3.83
3.74 4.22
0
5.0
3.0
9.9 6.2
10.1
-49
4.72
2.45
3.04
4.51
8.0
1.0
-
3.5
0
or to complex to afford
ned from glycals high-pressure
‘L 3.8 for
or even after
retro-addition
a
the starting not only
10.7
J13=0, J56=10.6, J66,=10.7
JS6,=5.4,
JS6=2.5, JS6,=6.5,
J33,-13.0, 510.8 J66’ J56-10.1,
JS6,=5.3, J66,=11.9
JS6=10.4,
JS6’=5.0,
JS6,=4.6,
.J66.=10.5
analysis
standing
and isocyanates
technique
forecasts
J55,=12.5
37
Upon heating
and this
by high pressure.
compounds 37 - 49
H-2
a not resolved
by a negative
the retro-reaction
at room temperature, This
glycala.
under thermal accelerates
fact
conditions.
the reaction
adducts
explains
2 - 8. _zfi - 30 and 34 underwent why f3-lactams
Moreover, rate
this
but also
could
observation allows
not be obtaishows that
to obtain
the
compounds
Scheme
2
AGO
--a
AC
2.
0
Scheme
3
/c
Ts
,N=&j%
H
R2
High-pressure (2 + 2) cycloaddition
thermodynamically us
for
forbidden
The rearrangement Such
2,
glycals
pression
to
competition perties
can
chair
of
owing
is
equilibrium that
the of
bicyclic 1)
geometry C-6
of
the
it
has
pyranoid
rigid
earlier
in
the
a part
been
of
stable
as
observed
by one
of
compared
of
high
the
pro-
derived
6-lactams
pressure.
from
derived After
rearrangement,
decom-
and this
with
the
rearrangement.
The
to
the
conformational
pro-
in
solution
related
This
group.
ring,
which
the
vicinal
coupling
and C-4
of
atoms.
an equatorial
occupies
the
by the
valence
also
to
not,
however,
the
of
representapyranoid
the
conformers
molecule
involved
It
can
or
pseudo-equatorial
a position
and di-
four-membered
between
conformation
The ratio carbon
requires N bond
is
as a distorted supported
constants
non-chair 2).
well of
belongs
-34 and 35
(Scheme
is
A distortion
protons.
adducts
C-3
-
under
from
conformation C-l
In case
over
characteristic
discussion.
a time-average
the
a very
B-lactams
-34 and -35 exists
pyranoid
forms
the
closely
ring
of
at
whereas
is
blocking
drawn
to
substitution
most
the
Examination either
favoured
is
bicyclic
only
is
adducts
pyranoid
model
half-chair
atom,
possible
additional in
of
was observed.
cycloaddition
ring
amide
behaviour
4,6-O-benzylidene
testifies
the
a.&unsaturated
is
deserves
two pseudo
carbon
the
retro-process
for
between
on the
to
and rearrangement
f3-lactams.
of
depends
the
the
The conformational
(Table
phenomenon
as a general
rearrangement
and
the the
introduced
system.
This
no retro-addition
barrier
constants
an equilibrium
tion
energy
f3-lactams,
coupling
protons
the
retro-addition
to
other
whereas
elevation
that
angles
B-lactam
a lower
ring
recorded
- 2J,
form
hedral
to
a
be assumed
of
ring
3,
bicyclic
values
tive
2,
pressure.
g-lactam
been
- &.2-4
between
of
It Cl
12
1.
the
has
and temperature
testifies
4
of
a reaction
dihydropyrans
normal
2447
isocyanafe to glycals
8
(4+2)cycloaddition.
cess.
from
at
of toluene4sulphonyl
be assumed,
favoured
by the
or in
the
however, posianomeric
effect. The mechanism enol et
ethers a1.9*10
posed
the
from
process
in
only
however,
to
the
acts
with
positioned valence
to
ford
36,
the
model
with
an enolic
of
the
stage
above
the
intermediate.
dipolar
The difference stituent opening in for
both the
attached of
the
Z trans
in
behaviour the
of
50°C
undergoes
the
2).
Also
between ring
with
of
the
without
the
5,
8,
28
suggest enol
g-lactams
C-l
form
to 39 _.
retarded.
the This
of
as
8,
form
of
bicyclic
2
- 30,
causes
(Scheme 1
a
2).
Such
(there
is
unsubstituted can
no di-
be easily
axial
3
l5),
acetoxyl
result
with as
of
the
at
from rather
a methyl
well
the
as
or
reac-
j?J which
corresponds
reaction
an intermediate 3).
shifts Alla1
rearrangement
an absence
(Scheme
from
decompression is
- 30, (7_,
6,
xylal
and C-5
high-pressure
it
from
hyb-
strains,
In case (5,
sp2
chair
ring.
trans
mechanism
5,
involving
at
of
torsional
atoms
obtained
before
amide
and those strongly
those
obtained
and hence
carbon
mo-
an electrocyclic
ring. atoms
derived
pyranoid
the
from
was pro-
simple
a distorted
position
and C-5
retro-reaction
of
free
axial
B-lactams
to
carbon
substituents
6-lactams
in monocyclic
the
and of
open-chain shift
is
of
The occurrence
four-membered
C-4
cycloaddition
the
3).
from
Effenberger
same pathway
probably
molecule
cycloadduct
the
electrocyclic
methanol
to
experiments
to
2 and the
the
bicyclic is
and C-5
C-3,
of
because
rearrangement
a mechanism
equilibrium
the
of
high-pressure
the
C-l
atom
at
inversion
amides,
pyranoid ring
of
the
carbon
case
of
derived
detail.
isomerisation
ring
a conformation
part
cis-orientation
a concerted
to
Such
the
C-6
without
(Scheme
suggests
6-lactam
reactions. cis
at
by a rapid
amides
Such
at
in
(Schemes
B-lactams in
3);
the of
f3-lactam
ring
of
studied
(Scheme
properties
the
OAc and CH20Ac group)
mutual
unsaturated
unsaturated
the
been
explains
conformation
substituents
the
form
isocyanate
proposed
of
temperature
of
followed
in
be destabilized
between
Adducts
the
distorted
the
the
f3-lactam
atom.
a shift
well
of
trens-configuration
between
fails
the
nitrogen
angles
requires
tosyl
atom
a relative
into
the
not
rearrangement of
E.
Elevation
elucidate
does
changes
repulsion
tion
it
The
rearrangement has
as an intermediate
intermediate
enolization
a conformation
transformed
form
carbon
C-Z
repulsion
hydropyran
dipolar
the
amides
The dipolar
follows
enolization
1,3-diaxial
the
and of
a,6-unsaturated
the
having
1,3-diaxial
isomerisation to
dihydropyrans.
an equatorially
leaving
z),
postulated
or
which
6-lactams
cis-crens
isocyanate
rearrangement.
B-lactams;
glycals
ridization with
the
tosyl
have
for
nocyclic
of
and
C-3
to
well
g-lactams than
one
oxyalkyl
reafwith to via
sub-
stereospecificity
dipolar can
intermediate also
be proposed
of
2448
M.
Table5.
CHMleLewSKI
Analytical data for adducts 2 - 8, a
Substrate
Temp. oC
1.
RT
r
50
Productsb
IR cm-1
5 2
43
1800
+80.3O
102-104
-38
Q5
1600, 1695
c
c
75
1805
25
1605, 1695
77
1805
2
RT
a
RT
I
3
50 RT
II
RT
-16
RT
-17
RT
-18
RT
-20
50
- -*35 37 and -39a
Yield %
2
4
et uf.
59
c
1810
21. Lv951, X(5)
-11o.oo c -110.00
syrup
89-90 c 95-97
x(25)
65
1815
c
c
29(65), x(35)
81
1800
c
c
1810
c
syrup
71
1810
c
c
50
1605, 1695
+77.8O
98-101
2(75),
30 24(50). X(50) 39
_ a elemental analysis of compounds shown in this table are not consistent due to the instability of material obtained b c
ratios of isomers given in brackets are taken from the 'H NMR spectra crude product or a mixture of products
Table 6. Analytical data for compounds 40 - 49
Substrate
Product
(aI" c=l, CHCl
3
IR
M.P.
Molecular
cm-1
oc
formula
-40
+45.oo
3370, 1750
-41
+16.60
3360, 1750
42
-29.2'
3370, 1755
-43
-60.60
3380, 1755
-44
+5.6'
3240, 1740
50.3
5.4
2.8
a
C2l"ZPllNS
50.3
5.4
2.8
49.7
5.5
2.8
79-82
C18"2309NS
50.3
5.4
3.3
50.0
5.4
3.4
58-60
C19H2509NS
51.5
5.7
3.2
51.4
5.8
3.2
49-54
C19H2509NS
51.5
5.7
3.2
a
a
a
53.0
6.0
3.6
a
a
a
55.2
8.8
1.9
55.0
9.1
2.0
61-65
a
NW
Czl"z7OllNS
92-93
3240, 1740
45.46
Elemental analysis Found Calcd. CX H% NX C% HX
a
49
-7.Z"
3240, 1730
93-98
C17H2307NS C33H6308NSSi3
-47
-10.50
3240, 1725
167-169
C22H2507NS
59.0
5.6
3.1
59.1
s.7
3.3
-48
+42.4O
3250, 1725
219-221
C22H25O7NS
59.0
5.6
3.1
58.7
5.7
3.5
a samples of 40, 44 and the mixture of -45 and -46 obtained from different experiments and which vere identical (TLC, IR and lH NMR data) gave inconsistent elemental analyses
High-pressure (2 + 2) q&addition
of toluene4sulphonyl
isocyanate to glycals
2449
EXPERIMENTAL Melting points are uncorrected. ‘H NMRspectra were recorded for CDClr solutions with a Jeol JNM-4H-100, Bruker WH-270 or Bruker WM-500 spectrometer (6 scale, ‘I%=0 ppm). ‘? NMRspectra were obtained on a Varian CFT 20 spectrometer. Optical rotations were measured with a Perkin-Elmer 141 spectropolarimeter. IR spectra were recorded on a Beckman 4240 spectrophotometer. Gravity column chromatography was performed on Merck Kieselgel 60 (230-400 mesh). TLC was performed on Merck DC Alufolien Kieselgel 6OF-254. A mixture of diastereoisomers 29 and 33 were obtained according to the procedure described earlier.’ General method of the high-pressure cycloaddition. Reactions between glycals 1 - 5, 2, 24 - z and toluene-4-suluhonvl isocvanate were carried out for 18 - 20 h in absolute ethvl ether as solvent. at room or 50°C temperature under 10 - 11 kbar. The reaction mixture: 1 mm01 of glycal, 1.5 mm01 of the isocyanate and 2.5 ml of ethyl ether was placed in a Teflon ampoule which was inserted into the high-pressure vessel filled with hexane as a transmission medium. After decompression, the mixture was diluted with absolute ethyl ether (10 ml), dry pentane was added until the solution became clouThe crystalline cycloadduct precipitated from dy, and then it was left at refrigerator overnight. the post-reaction mixture, was isolated by filtration and characterized as crude solid (Table 5). Ratios of diastereoisomers were determined from the rH NMRspectra. General method of methanolysis of the bicyclic B-lactams. A bicyclic 8-lactam (0.5 mmol) was treated with 5 ml of methanol and left at room temperature for 1 h. Subsequently the solvent was evaporated and the product was purified by chromatography to give the appropriate methyl glycoside in about 70% yield (Table 6). Diastereoisomeric glycosides separated -47 and -48 were chromatographically into pure components. Acknowledgments for
recording
- The authors
wish to thank Dr. Klaus Bock (The Technical
the ‘H NMRspectra.
This work was supported
by the Polish
University
of Denmark)
Academy of Sciences
grant
MR - I - 12. REFERENCES 1. M. Chmielewski, (1984). 2. E. Effenberger
2.
Kaluba,
C. Betiecki,
and R. Gleiter,
3. A. G. M. Barrett,
P. Saranski
Chem. Ber.,
97,
A. Fenwick and M. J. Batts,
4. J. H. Chan and S. S. Hall,
and J. Jurczak,
and W. C. Meyer,
7. T. Asano and W. J. 8. J. Jurczak,
leNoble,
T. Kotluk,
S. Filipek
9. E. Effenberger,
P. Fischer,
10. E. Effenberger,
G. Prossel
J. Org. Chem., 36,
Chem. Rev.,
78,
G. Prossel
4797
Chem. Commun., 299 (1983)
Perkin
I,
38 (1973):
R. H. Ha.ll,
2841 (1971).
407 (1978).
and C. H. Eugster, and G. Kiefer,
and P. Fischer,
25,
195 (1984).
5. k. H. Hall, A. Jordaan and G. J. Laurens, J. Chem. Sot., daan and 0. G. de Villiers, Ibid., 626 (1975). 6. E. J. Moriconi
Lett.,
1576 (1964). J. Chem. Sot.,
J. Org. Chem., 49,
Tetrahedron
Chem. Ber.,
Helv.
Chim. Acta,
Chem. Ber., 104,
104,
2002 (1971).
66,
222 (1983).
1987 (1971).
A.Jor-
HIGH-PRESSURE
(2tZ)CYCLOADDITION OF TOLUENE-4-SULPHONYL ISOCYANATE TO GLYCALS
Marek CBMIELEWSKI~ Zbigniew KAKUkA, Czesraw BEKiECKI, Piotr SAZANSKI,
Janus.2
JURCZAK and Halina AD~OWI~§
Institute
Polish Academy of Organic Chemistry, 01-224 Warszava, Poland
of Sciences,
(Received in UK 26 February 1985)
Abstract - High-pressure (2+2)cycloaddition of toluene-4-sulphonyl isocyanate to glycals is examined. Reactions proceed regiospecifically to afford single products in case of all 3-substituted glycals. Upon heating or even after standing at room temperature adducts undergo retro-addition to give starting glycals. Various aspects of the cycloaddition are discussed, especially retro-reaction and rearrangement of B-lactams to a,S-unsaturated amides. Recentlywe
have reported on high-pressure ~2t2)cycloaddition of toluene-4-sulphonyl isocyanate to
glycals 1 - &.l The reaction proceeds regio- and stereospecifically to afford a B-lactam ring in position trans to the acetoxy group at C-3 of the glycal moiety (5 - 8). Owing to the enol ether structure of glycals, cycloaddition offers an approach to various g-lactams, particularly to oxapenams and oxacephams. Owing to the stereospecificity of the reaction, glycals of D-series 1. and 2 lead to S-configuration at the carbon atom
attached to the nitrogen and oxygen atom, whereas glycals of L-series 3 and
i lead to R-configuration at the C-l carbon atom. This offers stereocontrol in formation of an appro priate configuration at the carbon atom crucial for the biological activity of f3-lactam antibiotics. Cycloaddition of tosyl isocyanate to dihydropyran 2 at low temperature ('LOOC)and atmospheric pressure leads to formation of bicyclic f3-lactam-15. Elevation of the temperature of cycloaddition 3 2 causes a rearrangement of the four-membered ring to open-chain amide -21. Recently Barrett et al. have found that 2,2,2-trichloroethylsulphonyl,
2,2,2-trichloroethoxysulphonyl
isocyanate react with dihydropyran 2 to give unsaturated amides 19 - 2.
and trifluoroacetyl
no B-lactam being isolated
in all three cases. Similar results have been reported by Chan and Hall4 for the addition of tosyl isocyanate to dihydropyrans 12 - -14. The 5-substituted dihydropyrans 2
and -11 have, however, been
found to react with trifluoroacetyl isocyanate to give the expected S-lactams 16 and l7, respecti3 vely, obtained after cleavage of the trifluoroacetyl group with silica-gel. Attempts
at adding chlorosulphonyl isocyanate to glucal 1 have failed to give the expected !3-let5
tam; isocyanate acted only as a Lewis acid, causing the known dimerisation of the sugar substrate.
The aim of the present work was to elucidate the stereochemistry of (2+2)cycloaddition of tosyl isocyanate to glycals, as well as to interpret the chemical properties of the bicyclic B-lactams synthetized. Therefore we selected a wide and representative group of glycals. namely 1 - 5 and -22 -3. RESULTS AND DISCUSSION All cycloadditions. except that to 23, were performed in absolute ethyl ether either at room temperature or at SO'C, under 10 - 11 kbar pressure. Cycloaddition to glycals 1. 3. A, 21. 23, 25 and 27_ proceeded with formation of products which crystallized from the post-reaction mixture, vhereas
9 Permanent address: Department of Chemistry, Technical University, Warszawa, Poland 2441
M. CHMIELEWSKI
2442
Chart
er al.
1
/
Ts
AcC) 1: R1=OAc,R2=H
3:
R=H
5:
2: R1=H,R2=OAc
3:
R=CH3
5: R'=H,R'=OAc
R1=OAc,R2=H
7: R=H 8: R=CH3
R’
Q0
bR3
R3
(-$R2
R2
9. Rl,R2,R3,H -. -10: R1=R3=H,R2=CH3
d 12:
R1,R2=R3,CH3
u:
12: R1=R3=H,R2=OCH3
11: R1=R3=H,R2=CH2Ph z:
R1=H.R2=Ts
16: R1=CH3,R2=H
R1=R3=CH3,R2=OCH3
G:
R1=CH2Ph,R2=H
Is: R=Ts -19: R=CC13CH2S02 &I: R=CC13CH20S02 u:
R=COCF3
R’
9 R3
R
N--TS
/
-22: R1=CH20Ac,R2=OAc,
25: R1=R2=H
R3=H -23: R1=CH20Ac,R2=R3=H
a:
R1=H,R2=OAc
-* 24. R1=CH20SiMe2t-Bu,
3:
R1=OAc,R2=H
R2=R3=OSiMe
2
-28: R1=CH20Ac.R2=0Ac, R3=H
-31
-29: R1=CH20Ac,R2=R3=H 30: R1=CH20SiMe2t-Bu, R2=R3=OSiMe t-Bu 2
t-Bu
AGO R&Ts
PhC(q,Ts
PhC($$,fTs Y-2 AcO
d 2:
R1=CH20Ac.R2=0Ac
33: R1=CH20Ac,R2=H
-34
-35: R1=H 2: R1=OAc
CONHTs 37
High-pressure (2 + 2) cycloaddition of tolucne4sulphonyl derived
the products
from galactal
0-Benzylideneglucal Cycloadditions of addition 2.
proceeded
to glycals
both isomeric
regiospecifically.
were obtained
5),
-35 were obtained. determined
from the ‘H NMRspectra
In case
more polar
of
obtained
of cycloaddition
to 2,
g-lactam,
and it
of high-pressure
room temperature
of all
with the respective
Alla1 tained
shift
of
21 did not react
as the unique
The gross (Tables
of
For assignment
between these
be explained mation of (Table
towards
of
xylal.
by cooling
of
materials
after
Raising
separation of the tem-
the reaction
vessel
However, all
amides (5-10X);
the temperature
5).
with a minute amount of
of cycloaddition.
a,&unsaturated
Elevation
the isocyanate
products
we examined the respective rity
followed
were
Table
of solvent.
of starting
from the mother liquor
the yield
g-lactams
Experimental,
to
reaction
one of which (8)
of cycloaddition
was
to 2. cau-
amide 2.
at room temperature,
whereas at 50°C amide -39 was ob-
product.
structure
1 and 2).
the reaction with
also
Ex-
33. 3& -*
of diastereoiso-
evaporation
traces
as 3-N-tosylcarbamoyl
increased
and identified.
(cf.
careful
contained
32. _* 29 _*
of isomeric
isolated
after
low (cf.
28 _I
the mixtures
ratios
1 was contaminated
to 50°C,
by chromatography
sed a significant
materials
by chromatography
were contaminated
to rhamnal 3 the alternative
obtained,
products
was characterized
isolated
4.6-
of an addition
-23 and -25 was relatively
B-lactams
the product
mixtures
syrups.
of s (95%) over
of diastereoisomers
The approximate
as crude
decompression,
in case
2,
at room temperature
experiments
before
as crude
isomer 2, 6, 1 and 30 as a result
predominance
the crystalline
mixtures
were obtained
a single
mixtures
pure components.
compound -37 which was isolated
of crystalline perature
the respective
6 and -30 were characterized
post-reaction
(TLC).
into
(24)
whereas
respectively,
Owing to the instability
not be separated
All
yielding
to 3-deoxyglycals
and therefore
mers could
glucal
2443
conditions.
with substantial
of cycloaddition
Table
Cycloadducts
and silylated under these
l_, 2, 3 and 24,
products
Stereoselectivity
perimental,
(2)
26 was unreactive
isocyanate to glycals
of the l3 C NMRsignals
data of starting
two sets
of spectral
by introduction
the pyranoid
2 - 8 and 28 - -39 was determined glycals
data.
ring,
to appropriate
(Table
The upfield
of a four-membered which were also
ring
from the ‘H and 13C NMRspectra
into
exhibited
3).
carbon
atoms of
There is no, however,
shift
of C-3,
simila-
C-4 and C-5 resonances
the molecule
by the values
Blactams,
direct
and by changes of vicinal
can
in the confor-
coupling
constants
1).
The (2+2)cycloaddition
of
tosyl
isocyanate
to glycals
is
probably
a pseudo-concerted
reaction6
(Scheme 1). Scheme
The presence
of an a-substituent
cedifferentiation respect
to the
addition
glycal
was used.
All
g-lactams
tam ring
2.
is well
5 - g,
l5,
over
28 - 35,
oxymethyl treated
to give
stereospecifically
of
to specify
the diastereofa-
preferentially
trans
by the high stereoselectivity observed
(TLC),
could, one:
although
however,
in all
an excess
resulting
from trans
with
of cyclobe the result
reactions,
the star-
of the isocyanate
lower diastereofacedifferentiation, the adduct
and thus afforapproach
of
the iso-
group.
with methanol
the respective with
helps
enters
the alternative
mixture
23 and -25 exhibited with predominance
ring
expressed
The high stereoslectivity
to the terminal
the four-membered proceeded
This
atom greatly
The isocyanate
in the post-reaction
products,
respect
at C-3.
inglycals.
of one diastereoisomer
3-Deoxyglycals of
at the C-3 carbon bond
1. - 5 and 24.
was detected
with
ning of
group
stability
ded a mixture cyanate
the double
acetoxy
to glycals
of the lower ting
of
1
inversion
at room temperature,
glycosides
-40 - B. of the configuration
undergo a rapid
The opening at the C-l
of
ope-
the g-lac-
carbon
atom.
2444
Table
M. CHMIELEwsKlef a/. 1 H NMR data
1.
for
B-lactams
2 - 2 and 28
- 35
Comp .
H-l
H-2
H-3 H-3’
H-4
H-5
H-6 H-6’
J12
J23
2
5.88
3.55
5.27
4.91
3.67
4.01 4.20
6.2
3.1
6 1
6.03
3.40
a
a
a
a
5.3
5.3
-
a
-
5.84
3.51
5.26
4.90
3.48 3.97
-
6.2
2.7
-
5.9
-
8 28
5.85
3.52
5.22
4.71
3.48
1.12
5.3
2.4
-
5.4
-
7.5
J24=0.9,
5.00
3.35
2.00 2.30
4.87
3.67
4.16
5.5
6.1
2.6
4.2
3.5
3.3
IJ~~+J~~,
22
5.77
3.31
a
a
3.73
3.97 4.05
5.4
4.1
8.5
a
a
b
J56=4.5,
30
5.76
3.24
4.11
3.77
3.52
3.56 3.67
5.8
3.3
-
2.9
-
2.0
J24-;95;
‘34
‘3’4
‘45
-
5.6
-
7.7
J24=1.3, J66,-14.5
5.68
3.91
5.08
4.85
3.74
1.21
4.7
a.4
-
7.4
32
5.57
3.43
a
4.94
3.80
;.y;
4.6
/J23+J23,1
p34+J3,d
4.0
J56=5.3,
=16.7
-9.4
7.5
-33
5.69
3.40
a
a
a
3.83 3.88
5.6
2.0
6.8
a
a
a
-34
5.77
3.32
2.05 2.37
a
a
3.61 4.00
5.4
11.1
7.1
4.8
12.5
a
-35
5.79
3.25
1.86
a
a
4.23
4.8
8.8
6.9
3.7
11.6
a
not resolved
Table
a
2.
or too
13C NMR data
complex for
for
5 - 3,
adducts
J24=l
J56=7.2 [=a.3 J56,=5.8 J56=7.9,
2,
28,
22
37
- 35,
J56,=4.1,
.O
J33,=11.6,
IS
and Is,
(CDc13)
c-1.
80.42
80.29
79.91
80.99
89.48
165.53
80.24
al.19
80.31
80.31
79.78
160.62
C-2
51.78
49.79
51.36
52.47
46.53
108.00
45.63
45.97
48.81
45.22
48.80
103.84
C-3
66.86
65.48
66.42
66.77
23.79
20.65
23.41
21.43
a
23.68
C-4
66.65
62.86
65.37
72.04
18.44
18.60
66.50
16.82
a
73.21
C-5
69.49
68.72
60.72
67.40
57.94
66.50
71.89
67.43
66.59
64.11
a
61.38
C-6
62.71
61.58
-
la.22
-
-
64.26
65.91
65.81
68.58
a
-
not
Table
visible
3.
or
overlaped
13C NMR data
for
by absorptions
glycals
L-
4,
of
2,
a major
22,
23,
a 73.60
J35=2.2
(DM%-d6)
64.48 64.42
isomer
-25 - 21
(CDc13)
C-l
145.71
145.46
148.04
146.00
144.50
142.71
143.38
143.14
145.42
147.35
c-2
99.07
98.92
97.42
98.85
100.60
97.75
100.52
98.66
100.79
98.43
c-3
67.48*
63.81*
67.22
68.33
23.20
25.68
24.27
26.37
68.90*
62.01
c-4
67.28*
63.95*
63.62*
72.55*
19.90
65.69
19.21
75.11
77.01
76.05
c-5
74.04
72.84
63.47*
71.88*
65.80
73.96
72.72
69.97*
68.31*
64.93
C-6
61.40
61.95
-
16.56
62.41
66.23
68.99
68.90
68.60
assignments
may be reversed
-
J56,=6.0,
*
b )J45+J4.51=12.4
analysis;
J56,=6.7,
J24=1 .3
-31
-
J56-4.4,
a ::;
J66’ J56=6.6
a
*
‘23’
J66,=12.1
High-pressure (2 + 2) cycloaddition
of tolucne4sulphonyl
isocyanate to glycals
Chart 2
@e
Aches
ACQMe
42:
40: R1=OAc ,R*=H
R=H
t-BuMezSiO
&ONHT= -46
CONHTs
CONHTs
AGO
CONHTs
~ONHT~
47
Thespectral
data of the glycosides
@
- 49 (Table
4) help
to prove
the configuration
of bicyclic
B-lactams. It is well activation For
known that
volume,
Table Comp.
4.
acceleration
of
‘H NMRdata for
H-l
accelerates
enhances
the rate
of
volume varies
the reaction
reactions
characterized
, whereas it retards
the stereoselectivity
the activation
(2+2)cycloaddition,
significant
high pressure
and greatly
from -30 7
to -50 cm3/mol,
H-3 H-3’
H-4
H-5
H-6 J12 H-6 V
‘23
‘23’
‘34
J45
7.97
-
5.51
5.08
4.49 4.20
-
-
-
-
s
a
-38
7.85
-
5.66
5.23
4.59
4.14 4.35
-
-
-
a
a
39
7.71
-
5.69
3.89
4.36
3.04 4.54
-
-
-
3.4
10.6
-40
4.51
2.80
5.47
4.99
3.74
4.17 4.37
8.3
-
9.1
9.0
41 -42
4.44
2.85
a
a
3.86
a
8.2
10.8
-
a
a
4.12
2.70
5.43
4.97
a
-
7.6
10.0
-
9.5
5.3 9.0
43 -44
4.46
2.75
5.46 4.74
3.61
1.23
8.4
10.6
-
9.0
9.1
4.30
2.52
1.72 4.71 2.32
3.62
4.15 4.23
8.4
13.0
4.3
11.1 5.1
10.0
J s-13.6, J$=12.6
cs
4.25
2.22
a
a
3.61
4.06 4.13
8.6
12.4
4.3
a
2.0 11.5
J56=4.0,
-46
4.80
2.50
a
a
4.02
4.10 4.18
0
C]JI=10.9
a
3.4 11.5
-47
4.42
2.51
1.99 2.25
3.55
3.38
3.75 4.28
8.5
12.2
4.2
11.7 4.5
9.2
48
4.85
2.82
2.15
3.69
3.83
3.74 4.22
0
5.0
3.0
9.9 6.2
10.1
-49
4.72
2.45
3.04
4.51
8.0
1.0
-
3.5
0
or to complex to afford
ned from glycals high-pressure
‘L 3.8 for
or even after
retro-addition
a
the starting not only
10.7
J13=0, J56=10.6, J66,=10.7
JS6,=5.4,
JS6=2.5, JS6,=6.5,
J33,-13.0, 510.8 J66’ J56-10.1,
JS6,=5.3, J66,=11.9
JS6=10.4,
JS6’=5.0,
JS6,=4.6,
.J66.=10.5
analysis
standing
and isocyanates
technique
forecasts
J55,=12.5
37
Upon heating
and this
by high pressure.
compounds 37 - 49
H-2
a not resolved
by a negative
the retro-reaction
at room temperature, This
glycala.
under thermal accelerates
fact
conditions.
the reaction
adducts
explains
2 - 8. _zfi - 30 and 34 underwent why f3-lactams
Moreover, rate
this
but also
could
observation allows
not be obtaishows that
to obtain
the
compounds
Scheme
2
AGO
--a
AC
2.
0
Scheme
3
/c
Ts
,N=&j%
H
R2
High-pressure (2 + 2) cycloaddition
thermodynamically us
for
forbidden
The rearrangement Such
2,
glycals
pression
to
competition perties
can
chair
of
owing
is
equilibrium that
the of
bicyclic 1)
geometry C-6
of
the
it
has
pyranoid
rigid
earlier
in
the
a part
been
of
stable
as
observed
by one
of
compared
of
high
the
pro-
derived
6-lactams
pressure.
from
derived After
rearrangement,
decom-
and this
with
the
rearrangement.
The
to
the
conformational
pro-
in
solution
related
This
group.
ring,
which
the
vicinal
coupling
and C-4
of
atoms.
an equatorial
occupies
the
by the
valence
also
to
not,
however,
the
of
representapyranoid
the
conformers
molecule
involved
It
can
or
pseudo-equatorial
a position
and di-
four-membered
between
conformation
The ratio carbon
requires N bond
is
as a distorted supported
constants
non-chair 2).
well of
belongs
-34 and 35
(Scheme
is
A distortion
protons.
adducts
C-3
-
under
from
conformation C-l
In case
over
characteristic
discussion.
a time-average
the
a very
B-lactams
-34 and -35 exists
pyranoid
forms
the
closely
ring
of
at
whereas
is
blocking
drawn
to
substitution
most
the
Examination either
favoured
is
bicyclic
only
is
adducts
pyranoid
model
half-chair
atom,
possible
additional in
of
was observed.
cycloaddition
ring
amide
behaviour
4,6-O-benzylidene
testifies
the
a.&unsaturated
is
deserves
two pseudo
carbon
the
retro-process
for
between
on the
to
and rearrangement
f3-lactams.
of
depends
the
the
The conformational
(Table
phenomenon
as a general
rearrangement
and
the the
introduced
system.
This
no retro-addition
barrier
constants
an equilibrium
tion
energy
f3-lactams,
coupling
protons
the
retro-addition
to
other
whereas
elevation
that
angles
B-lactam
a lower
ring
recorded
- 2J,
form
hedral
to
a
be assumed
of
ring
3,
bicyclic
values
tive
2,
pressure.
g-lactam
been
- &.2-4
between
of
It Cl
12
1.
the
has
and temperature
testifies
4
of
a reaction
dihydropyrans
normal
2447
isocyanafe to glycals
8
(4+2)cycloaddition.
cess.
from
at
of toluene4sulphonyl
be assumed,
favoured
by the
or in
the
however, posianomeric
effect. The mechanism enol et
ethers a1.9*10
posed
the
from
process
in
only
however,
to
the
acts
with
positioned valence
to
ford
36,
the
model
with
an enolic
of
the
stage
above
the
intermediate.
dipolar
The difference stituent opening in for
both the
attached of
the
Z trans
in
behaviour the
of
50°C
undergoes
the
2).
Also
between ring
with
of
the
without
the
5,
8,
28
suggest enol
g-lactams
C-l
form
to 39 _.
retarded.
the This
of
as
8,
form
of
bicyclic
2
- 30,
causes
(Scheme 1
a
2).
Such
(there
is
unsubstituted can
no di-
be easily
axial
3
l5),
acetoxyl
result
with as
of
the
at
from rather
a methyl
well
the
as
or
reac-
j?J which
corresponds
reaction
an intermediate 3).
shifts Alla1
rearrangement
an absence
(Scheme
from
decompression is
- 30, (7_,
6,
xylal
and C-5
high-pressure
it
from
hyb-
strains,
In case (5,
sp2
chair
ring.
trans
mechanism
5,
involving
at
of
torsional
atoms
obtained
before
amide
and those strongly
those
obtained
and hence
carbon
mo-
an electrocyclic
ring. atoms
derived
pyranoid
the
from
was pro-
simple
a distorted
position
and C-5
retro-reaction
of
free
axial
B-lactams
to
carbon
substituents
6-lactams
in monocyclic
the
and of
open-chain shift
is
of
The occurrence
four-membered
C-4
cycloaddition
the
3).
from
Effenberger
same pathway
probably
molecule
cycloadduct
the
electrocyclic
methanol
to
experiments
to
2 and the
the
bicyclic is
and C-5
C-3,
of
because
rearrangement
a mechanism
equilibrium
the
of
high-pressure
the
C-l
atom
at
inversion
amides,
pyranoid ring
of
the
carbon
case
of
derived
detail.
isomerisation
ring
a conformation
part
cis-orientation
a concerted
to
Such
the
C-6
without
(Scheme
suggests
6-lactam
reactions. cis
at
by a rapid
amides
Such
at
in
(Schemes
B-lactams in
3);
the of
f3-lactam
ring
of
studied
(Scheme
properties
the
OAc and CH20Ac group)
mutual
unsaturated
unsaturated
the
been
explains
conformation
substituents
the
form
isocyanate
proposed
of
temperature
of
followed
in
be destabilized
between
Adducts
the
distorted
the
the
f3-lactam
atom.
a shift
well
of
trens-configuration
between
fails
the
nitrogen
angles
requires
tosyl
atom
a relative
into
the
not
rearrangement of
E.
Elevation
elucidate
does
changes
repulsion
tion
it
The
rearrangement has
as an intermediate
intermediate
enolization
a conformation
transformed
form
carbon
C-Z
repulsion
hydropyran
dipolar
the
amides
The dipolar
follows
enolization
1,3-diaxial
the
and of
a,6-unsaturated
the
having
1,3-diaxial
isomerisation to
dihydropyrans.
an equatorially
leaving
z),
postulated
or
which
6-lactams
cis-crens
isocyanate
rearrangement.
B-lactams;
glycals
ridization with
the
tosyl
have
for
nocyclic
of
and
C-3
to
well
g-lactams than
one
oxyalkyl
reafwith to via
sub-
stereospecificity
dipolar can
intermediate also
be proposed
of
2448
M.
Table5.
CHMleLewSKI
Analytical data for adducts 2 - 8, a
Substrate
Temp. oC
1.
RT
r
50
Productsb
IR cm-1
5 2
43
1800
+80.3O
102-104
-38
Q5
1600, 1695
c
c
75
1805
25
1605, 1695
77
1805
2
RT
a
RT
I
3
50 RT
II
RT
-16
RT
-17
RT
-18
RT
-20
50
- -*35 37 and -39a
Yield %
2
4
et uf.
59
c
1810
21. Lv951, X(5)
-11o.oo c -110.00
syrup
89-90 c 95-97
x(25)
65
1815
c
c
29(65), x(35)
81
1800
c
c
1810
c
syrup
71
1810
c
c
50
1605, 1695
+77.8O
98-101
2(75),
30 24(50). X(50) 39
_ a elemental analysis of compounds shown in this table are not consistent due to the instability of material obtained b c
ratios of isomers given in brackets are taken from the 'H NMR spectra crude product or a mixture of products
Table 6. Analytical data for compounds 40 - 49
Substrate
Product
(aI" c=l, CHCl
3
IR
M.P.
Molecular
cm-1
oc
formula
-40
+45.oo
3370, 1750
-41
+16.60
3360, 1750
42
-29.2'
3370, 1755
-43
-60.60
3380, 1755
-44
+5.6'
3240, 1740
50.3
5.4
2.8
a
C2l"ZPllNS
50.3
5.4
2.8
49.7
5.5
2.8
79-82
C18"2309NS
50.3
5.4
3.3
50.0
5.4
3.4
58-60
C19H2509NS
51.5
5.7
3.2
51.4
5.8
3.2
49-54
C19H2509NS
51.5
5.7
3.2
a
a
a
53.0
6.0
3.6
a
a
a
55.2
8.8
1.9
55.0
9.1
2.0
61-65
a
NW
Czl"z7OllNS
92-93
3240, 1740
45.46
Elemental analysis Found Calcd. CX H% NX C% HX
a
49
-7.Z"
3240, 1730
93-98
C17H2307NS C33H6308NSSi3
-47
-10.50
3240, 1725
167-169
C22H2507NS
59.0
5.6
3.1
59.1
s.7
3.3
-48
+42.4O
3250, 1725
219-221
C22H25O7NS
59.0
5.6
3.1
58.7
5.7
3.5
a samples of 40, 44 and the mixture of -45 and -46 obtained from different experiments and which vere identical (TLC, IR and lH NMR data) gave inconsistent elemental analyses
High-pressure (2 + 2) q&addition
of toluene4sulphonyl
isocyanate to glycals
2449
EXPERIMENTAL Melting points are uncorrected. ‘H NMRspectra were recorded for CDClr solutions with a Jeol JNM-4H-100, Bruker WH-270 or Bruker WM-500 spectrometer (6 scale, ‘I%=0 ppm). ‘? NMRspectra were obtained on a Varian CFT 20 spectrometer. Optical rotations were measured with a Perkin-Elmer 141 spectropolarimeter. IR spectra were recorded on a Beckman 4240 spectrophotometer. Gravity column chromatography was performed on Merck Kieselgel 60 (230-400 mesh). TLC was performed on Merck DC Alufolien Kieselgel 6OF-254. A mixture of diastereoisomers 29 and 33 were obtained according to the procedure described earlier.’ General method of the high-pressure cycloaddition. Reactions between glycals 1 - 5, 2, 24 - z and toluene-4-suluhonvl isocvanate were carried out for 18 - 20 h in absolute ethvl ether as solvent. at room or 50°C temperature under 10 - 11 kbar. The reaction mixture: 1 mm01 of glycal, 1.5 mm01 of the isocyanate and 2.5 ml of ethyl ether was placed in a Teflon ampoule which was inserted into the high-pressure vessel filled with hexane as a transmission medium. After decompression, the mixture was diluted with absolute ethyl ether (10 ml), dry pentane was added until the solution became clouThe crystalline cycloadduct precipitated from dy, and then it was left at refrigerator overnight. the post-reaction mixture, was isolated by filtration and characterized as crude solid (Table 5). Ratios of diastereoisomers were determined from the rH NMRspectra. General method of methanolysis of the bicyclic B-lactams. A bicyclic 8-lactam (0.5 mmol) was treated with 5 ml of methanol and left at room temperature for 1 h. Subsequently the solvent was evaporated and the product was purified by chromatography to give the appropriate methyl glycoside in about 70% yield (Table 6). Diastereoisomeric glycosides separated -47 and -48 were chromatographically into pure components. Acknowledgments for
recording
- The authors
wish to thank Dr. Klaus Bock (The Technical
the ‘H NMRspectra.
This work was supported
by the Polish
University
of Denmark)
Academy of Sciences
grant
MR - I - 12. REFERENCES 1. M. Chmielewski, (1984). 2. E. Effenberger
2.
Kaluba,
C. Betiecki,
and R. Gleiter,
3. A. G. M. Barrett,
P. Saranski
Chem. Ber.,
97,
A. Fenwick and M. J. Batts,
4. J. H. Chan and S. S. Hall,
and J. Jurczak,
and W. C. Meyer,
7. T. Asano and W. J. 8. J. Jurczak,
leNoble,
T. Kotluk,
S. Filipek
9. E. Effenberger,
P. Fischer,
10. E. Effenberger,
G. Prossel
J. Org. Chem., 36,
Chem. Rev.,
78,
G. Prossel
4797
Chem. Commun., 299 (1983)
Perkin
I,
38 (1973):
R. H. Ha.ll,
2841 (1971).
407 (1978).
and C. H. Eugster, and G. Kiefer,
and P. Fischer,
25,
195 (1984).
5. k. H. Hall, A. Jordaan and G. J. Laurens, J. Chem. Sot., daan and 0. G. de Villiers, Ibid., 626 (1975). 6. E. J. Moriconi
Lett.,
1576 (1964). J. Chem. Sot.,
J. Org. Chem., 49,
Tetrahedron
Chem. Ber.,
Helv.
Chim. Acta,
Chem. Ber., 104,
104,
2002 (1971).
66,
222 (1983).
1987 (1971).
A.Jor-