Tetrahedron Letters,Vo1.26,No.47,pp Printed in Great Britain
NARGENICIN
MODEL
5845-5848,1985
: DEHYDRATIVE
STUDIES
0040-4039/85 $3.00 + .OO @1985 Pergamon Press Ltd.
REARRANGEMENT
OF A DIHYDROXYOCTAHYDRONAPHTHALENE
Raymond
C.F.
Jones*
(Department
and John H. Tunnicliffe
of Chemistry,
Nottingham,
Summary
- Cyclic
ether
formation
The University,
NG7 2RD).
by dehydration
5-acetyl-1,5-dihydroxyoctahydronaphthalene ment
to give
of a cis-fused
occurs
with
a 12-oxatricyclo[5.4.11'7.03'a]dodecene
the ll-oxatricyclo[4.4.11'6.02'7
lundecene
system
rearrangerather
than
of the nargenicin
antibiotics. The nargenicin nodusmicin(lb),l ting macrolide The novel
antibiotics,
comprise
reports
(la) and
biomimetic3)
C-8,13
The strategy
a highly
linkage
us to report
we adopted
is outlined
functionalised
ether
include
and
of structurally
antimicrobial
functionalised
fascina-
activity. oxygen-bridged
(ll-oxatricyclo[4.4.11'6.02'7]undecene) nucleus. 2 of such a moiety, and on the biosynthesis
below
of a cis-octahydronaphthalene a highly
group
significant
Al(la)
of the synthesis
(1b),3 have prompted
this area.
by nargenicin
identified
displaying
features
cis-octahydronaphthalene Recent
a recently
antibiotics
structural
represented
(2), and
macrolide
a;
Diels-Alder
elaboration.
R= 0,s !
b; R=H
features
(b) the subsequent
(11
R’OZC
5845
studies
now may be regarded
and has as its central by intramolecular
triene
before
on our own synthetic
(and which
of
in
as
(a) formation
cycloaddition closure
of the
of
5846
Although
our expectation
addition
of
we chose
to confirm
formation
(2), leading
to the required
this prediction
on a simplified
prepared
as follows.
4-bromobutanal
4 h; 87%L5 aldehyde
model
Addition
diethyl
a hydroxy-acetal
acetal
(83%)4a
(CH2C12;5
for the exo-mode
cis-ring
system.
reflux,
was well-precedented,*
methodology
reagent
for the ether
prepared
(2E,4E)-hexa-2,4-dienal
of the acetal
of cyclo-
To this end the trienone
of the Grignard to
fusion,
and to examine
that was acetylated
Hydrolysis
(3a) (94%J5 which
phorane
of a preference
from
(THF, O'C) afforded
(Ac20, Et3N,
(5%[CO2H]2-H20;
(4) was
catalytic
25'C,
DMAP;
25'C,
48 h) produced
was condensed
with
2-oxopropylidenetriphenylphos-
4.5 h) to give
the
E,E,-trienone
an
(4) (69% after
chromatography). The intramolecular accomplished
chromatographic as a mixture efficient which
1 h, then
with
140°C,
(90%).
of trienone
dry xylene
(54%) and unchanged proceeded
trienone
directly
the cycloadduct
After
be
12 h
cycloadduct (28%).
(5j5
A more
from the dienal
2-oxopropylidenetriphenylphosphorane
5 h) afforded
(41, could
at 130°C.
the octahydronaphthalene
for cycloaddition
in xylene
(3a),
(lOO'C,
(5) as the same mixture
of
Further
separation by preparative h.p.1.c. gave the 5 (6a) with the desired.cis-ring fusion and a-acetoxy
octahydronaphthalene stereochemistry with
yielded
of stereoisomers
protocol
cycloaddition
in oxygen-free
separation
on heating
isomers
Diels-Alder
by heating
as the major
the benzoate
(3bj5 gave
single
isomer
similar
(37%).6
results
Repetition
of this
but a less convenient
sequence
separation.
The assignment of the illustrated stereochemistry to this major adduct 1 on H n.m.r. studies at 250 MHz (CDC13) on both acetate (6a) and
is based
the alcohol
(6bJ5 obtained
hydrolysis].
from
These
indicate
5, and 6, and an equatorial confirmed although
it after
(6a), excluding
(6b) regenerated
basic
methanolysis
the possibility
inter
alia
proton
the presence
at C-1.6
[acetylation
of epimerisation of axial
The relative
of
during
protons
at C-4a,
configuration
was
as
(6) by an _ X-ray crystal structure determination of alcohol the crystal conformation (Fig.1) is different to that observed
(6b),8 in
solution. The introduction initially give
radical
allylic
hydrogen
only
to afford
Attempted
the undesired
C-5 was eventually
achieved
ButOK,
35'C,
ButOH,
and recovered
02;
Acid-catalysed ether
formation,
but
a cyclohexene
then
dehydration
of
of
reqioisomer
by base-catalysed
20 min.
instead
(6b), for example,
halogenation
(6b) (33%); 10 convex face.
at C-5 for ether with
formation
Pb(OAc14
was
did not
from C-5 but instead
monobromo
alcohol
the less hindered
of
abstraction
fragmented
regioisomer).
afforded
functionality
Treatment
unsuccessful.
the desired
alkoxy
of suitable
(815.
oxygenation
Zn, AcOH)
the oxygen
the intermediate 5 (or its derivative (7) 9 (6a) by various methods
to give
insertion
(9) (HCl, CH2C12;
of the required
Functionalisation of acetate the diol
(9) (40%j5
was assumed
25'C,
at
(6a)
to be from
16 h) did lead to
ll-oxatricyclo[4.4.11'6.02'7]-
5841
OR CHO (3)
a;
R = COMe
b; R = COPh A
/
ti
OCOMe (6)
15)
a;
R= COMe
b;
R=H
CHO
Br
jg,,H(jgH ii
Fig. 1
MeCOO
(7)
HO
CfY 0
‘I “H
l4
(10)
undecene
system,rearrangement
12-oxatricyclo[5.4.11'7.03'8 studies.
A reasonable
a 1,2-shift ment
ldodecene
pathway
in the hemi-acetal
and further
presently
occurred
efforts
underway.
to afford
(10) (58%).5
formulation
is supported
for the production (ll).ll
to close
Studies
the ether
of this novel
This by n.0.e. system
invokes
on the scope of this rearrange-
bridge
without
rearrangement
are
5848
References
1.
(a)
and Notes
W.D. Celmer, G.N. Chmurny,
J.Am.Chem.Soc.,
1980, c,
R.J. Wnuk, Tetrahedron
C.E. Moppett,
4203;
Lett.,
represents
the three-dimensional
from that usually
J. Kallmerten,
3.
(a) D.E. Cane and C. Yang, J.Am.Chem.Soc.,
4.
ibid., p.787;
assessed 6.
1982, 47,
1984, 106, 784;
combustion
1985, 38, 423.
1981, 103, 5200,
(b) R.L. Funk and
180.
analysis
or accurate
with the assigned
mass measurement.
structure,
Purity was also
by t.1.c. examination.
The signal for H-5 in (6a) (62.84, dd) showed J 9.1 and 10.8 Hz, whilst (63.05, dd) had J 9.5 and 11.3 Hz. The resonance spin-spin
7.
of drawing
W.C. Snyder and K.L.
(IR, UV, NMR, MS) consistent
gave spectra
and satisfactory
the method
employed,
(c) D.E. Cane and C. Yang, J.Antibiot.,
J.Orq.Chem.,
All new compounds
In particular,
and
in (1)
1984, 25, 2843.
(a) W.R. Roush, and S.E. Hall, J.Am.Chem.Soc., W.E. Zeller,
5.
Lett.,
S.A. Mizsak,
illustrated
but we feel it better 3c This has also been noted elsewhere.
structure.
2.
Rinehart,
C.G. Chidester,
The stereochemistry
shown in ref.l(b).
at C-2 differs
Tetrahedron
R.S. Ware, P.C. Watts, and E.B. Whipple,
H.A. Whaley,
1980, 1_1, 3659.
is based on the Ij-ray structure the configuration
(b)
coupling
Also isolated
of sufficient
were the a-acetoxy
magnitude
for
H-l
to represent
epimer of (6a)(13%),
that in (6b
in (6a) and (6b) showed no an axial-axial
and a mixture
arrangement
of two a-fus'
ed
isomers. 8.
This determination details
triclinic
system,
separately.
c = 12.230(2);,
u.= 98.97(l)', The structure
at an earlier
pyrrolidine
series;
hydrotribromide,
stage, by using
olefination-cycloaddition
and refined
and full
crystallised
a = 6.411(l),
in the
b = 8.207(l),
and y = 110.41(1)0 with two molecules from 1643 observed
reflections
by direct
to R = 5.19%. Br2-AcOH,
Inclusion
and CuBr2.
I-halo-2-oxopropylidenetriphenylphosporanes
sequence
the major cycloadduct
(Nottingham)
(6b), C,3H2002,
B = 97.12(l)', was determined
using the MULTAN program
These included
by Dr. M.J. Beqley
Alcohol
space group P-i, cell dimensions
per unit cell. methods 9.
was kindly performed
will be reported
with dienal
in the
(3a), led to decomposition
in the chloro-series
was assigned
of a halogen
in the bromo-
the undesired
trans-
ring fused configuration. 10. 11.
E.J. Bailey,
D.H.R. Barton, J. Elks, and J.F. Templeton,
The hemi-acetal
(11) is chosen on the basis of stereoelectronic
C-C bond and a lone pair on the bridging breaking
C-O bond
Pergamon
Press, Oxford,
(Received
J.Chem.Soc.,
(see P.Deslonqchamps, 1983).
in UK 30 September
1985)
1962, 1578.
effects:
the migrating
oxygen atom are both antiperiplanar 'Stereoelectronic
Effects
in Organic
to the Chemistry,'