Reductive dechlorination of gem-chlorofluorocyclopropanes with lithium aluminium hydride. A stereoselective process.

TetrahedronLetters No. 27, pp 2483 - 2486, 1973.

REDUCTIVE

DECHLORINATION

LITHIUM ALUMINIUM

Pergmmm Press.

Printed in Great Britain.

OF gem-CHLOROFLUOROCYCLOPROPANES

HYDRIDE.

Charles Wllllam

A STEREOSELECTIVE

Jefford*,

WITH

PROCESS.

Ulrlch Burger,

Mostyn Henry Laffer, and nTanda Kabengele, Department

of Organic Chemistry,

University

of Geneva, 1211 Geneva 4

(Reoeiredia UK 7 I&y 1973; acceptedfor publication24 I4q 1973)

We have recently reported expectations

that lithium aluminlum hydride

(LAH), contrary

of long standlng, can bring about reductive dehalogenatlon

wide variety of so-called

Inert organic halldes

ticular, gem-dihalocyclopropanes halocyclopropanes dlhalo grouping

undergo

and cyclopropanes2. appears to control

[4.l.O]heptane

(1) gives mainly

in high yields

stepwise dehalogenatlon

Furthermore,

the reduction

course.

of the gem-

the endo product 2, while 3,3-dlchlorotrlcyclo-

selective process,

taken together with the uncanny parallelism

the reactlvlty

In par-

7,7-Dibromobicyclo-

(2) gives chiefly the exo product 4.

of organotln

of a

to give mono-

the environment

[4.2.1.02'4] nonane

scopic behavlour

(>8O%)l.

to

hydrides

This hint of a stereoof the macro-

and LAH 1,3 , leads us to examine afresh

of gem-chlorofluorocyclopropanes

2483

on treatment with LAH4.

No. 27

2484 Two pairs of gn-ant1 and treated rndividually

isomers

(5, 8 and 2, -12) were prepared5,

with a threefold excess of LAH In dlglyme

In each case, reductive dechlorination

1.5 hours.

at 100° for

occurred quantitatively

give a pair of fluoro epimers in which the original (Table).

separated

skeleton remains

to

intact'

Not only 1s the second epimer formed in sizeable amounts under these

relatively mild reaction conditions,

but the isomer ratio clearly reveals the

operation of sterlc factors in the substrate.

For the z

and anti-fluoronor-

caranes 5 and 8, the overall course 1s one of retention of configuration fluorine-bearing more strained

carbon atom.

ant1 isomer 8.

Nevertheless,

less retention

is observed

The effect is more pronounced

pair 2 and 12 in which the G-disposed

substituents

bonded interactions

methylene

with the contiguous

for the

for the tricyclic

encounter

bridge.

at the

severe non-

The anti isomer 12 This

strll favours formation of retalned product, but to a less marked extent. trend away from retention stereochemical

takes a dramatic

tion of cyclopropyl

halides.

tive and not stereospecific

transition

as the recently proposed therefore

informative

Firstly,

states.

about the mechanism

the macroscopic

as previously

cannot be rationalized

two different

clalmed4.

process

Secondly,

the product

four-centre

operation

both SN1 and SN2 processes

mechanism

can all be ruled out4.

intermediate

which tends to retain its configuratlon,

rnvert If compelled to do so by virtue of intramolecular

carbanlon.

is stereoselec-

in terms of the simultaneous Obviously

of reduc-

of

as well It

follows that the results can only be explained by the formatlon of a

cyclopropyl

actions.

the overall

isomer 2;

course being inverslon of configuration.

These findings are particularly

composition

turn with 2

Only two intermedlates

fit these criteria;

but may

non-bonded

a cyclopropyl

interradical or

In both cases, direct attack by metal hydride on chlorine

account for their formation. ly react differently, aluminlum deuteride

However,

the two Intermediates

and in distinguishable

can

should subsequent-

fashion, especially

if lithium

(LAD) 1s used as reagent.

Taking compound i by way of illustration,

the derived cyclopropyl

radical

No.

W5

27

(13) and carbanion cal 13 confronted de and aluminium the protonic

(15) should display markedly with its immediate,

deuteride

rium chloride or aluminrum deuteride, deuterated

analoques

of 5 and 1 in which 100% incorporation

at the fluorine-bearing

occurs via a cyclopropyl -

carbanlons

the intermediacy (or even

radicals)

diqlyme at

of the mixture with dry pentane

cyclopropyl

carbanion,

of orqanometallic

of

carbon*.

that LAD and LAH reduction

of E-dihalo-

it is also seen that reduction

is already complete prior to the stage of the conventional Accordingly,

deute-

but not from the weakly acidic solvent.

Extraction

Apart from this strong indication cyclopropanes

from

In contrast,

from its most acidic neiqhbour,

8 was heated with LAD in anhydrous

100° for 1.5 hours under nitrogen.

had occurred

preferentially

product -16 is expected.

In the actual experiment,

deuterium

The radi-

(deuterium chlori-

isotopic product -14 should result.

the carbanion 15 will capture a deuteron

afforded the deuterio

behaviour.

but inert, environment

radical) will abstract hydrogen

solvent. A mixed

Thus the completely

different

compounds

aqueous work-up. derived

from

is most unlikely. REFERENCES

(1)

C.W. Jefford, D. Kirkpatrick (1972).

(2)

R.E. Erickson, R. Annino, M.D. Scanlon and G. Zen, J. Amer. Chem. Sot. 91, 1767 (1969); H. Yamanaka, R. Oshima, K. Teramura and T. Ando, J. Orq.Chem. 31, 1734 (1972); D. Seyferth, H. Yamazaki and D.L. Alleston, ibid. 2, 703 (1963); S.J. Cristol, R.M. Sequeira and C.H. DePuy, J. Amer. Chem. Sot. a?, 4007 (1965); W.E. Barnett and R.F. Koebel, Chem. Comm. 875 (1969).

(3)

T. Ando, F. Namiqata, H. Yamanaka and W. Fumasaka, J. Amer. Chem. Sot. as,

(4)

H. Yamanaka,

(5)

Compounds 2, 8, 2 and 12 were prepared by the addition of chlorofluorocarbene (ref. 6) to cyclohexene and bicyclor3.2.1]oct-2-ene. Separations were effected by gas chromatography (20% FFAP on Chromosorb W, 5 m, 800 and 5.0, 100°C. Structure assignments were based on the values of 3JFH, VlZ. 18.0, 6.0 and 20.0 Hz respectively.

(6)

P. Weyerstahl, D. Klamann, C. Finger, F. Nerdel and J. Bu-drus, Chem. Ber. 100, 1858 (1967).

(7)

All

(8)

(analogous to 1) The ma3or product, 7,7-deuteriofluorobicyclo[4.1.O]heptane showed values of 10.0 and 22.0 Hz for 2JFD and 3JFH respectively.

5719

(1967), J. Org. Chem. S,

and F. Delay, J. Amer. Chem. Sot. 94, 8905

33 (1970).

T. Yaqi, K. Teramura

and T. Ando, Chem. Comm. 380 (1971).

products were separated by q.c. and gave correct elemental and mass spectral anal ses. Structures of 6_, 1, 10 and 11 were attributed on the basis of the Y JFH values, viz. 68.0, 65x, 68.c 61.1 Hz and the cyclopro6.3, 2.0, 6.5 and 1.7 Hz respectively. pyllc 3JHH values, viz.

No.

2486

Table.

Reductive Dechlorination of Some Chlorofluorocyclopropanes with Lithium Aluminium Hydride Products

Reactant

94%

10%

”

Isomer Ratio

Anti

5Yn

6%

90%

Overall Course

15

Retention

9

Retention

F 17%

83%

5

Retention

29%

71%

25

InversIon

&IS 12

s

F

Cl

9

LAD dtglyme

DCI

27