Nargenicin model studiess: dehydrative rearrangement of a dihydroxyoctahydronaphthalene

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,'