Polar and solvent effects in the reduction of substituted cyclohexanones

l%l.

No. 12, pp. 404-409,

Tetrahedron Lstters in Great Britsin.

Pergamon Press Ltd. Printed

POLABAND SOLVENTEFFECTSIN THE REDUCTION OF SUBSTITUTEDCKLOHU(ANONES* Miss M.G. Combe and H.B. Henbest Department of Chemistry, The Queen’s

University

of Belfast,

(Received THE direction olefinic

of

bonds

direction

the effect

borohydride cular

reaction

transference

related

reducing

carried

out.

Unhindered, hydrides

to give

1

linear

reagent

being

agents,

diborane

substituted

equatorial being

alcohols formed

Some of the results reported Conference on Stereochemistry Edmonton, September 1960.

saturated

rings.

substituent

to carbonyl

and lithium

react

as main products, yield

In order

the ketone-

by intermolewith

hydride,

with for

1

upon the

experiments

aluminlum

cyclohexanones

on

bonds, we chose

as proceeding

Comparative

in SO-84

acid,

by borohydrides,

visualised

anions.

perlauric

by polar substituents,

dipolar

of chloro-cyclohexanones usually

alkyl

two or three

of a nucleoohilic

of hydride

4-methylcycloh~exanol

*

across

of a simple,

to study the reduction

reagent,

compounds can be influenced

are located

of addition

17 May 1961)

of the electroahilic

in cyclic

even when these to determine

attack

N.Ireland

the

were also

complex

example,

on reduction

a-

of L-methyl-

in this paper were presented at the held at the University of Alberta,

N.S. Cnossley, A.C. Darby, H.B. Henbest, and M.F. Stewart, preceding paper.

404

J.J.

McCullough,

B. Nicholls

Reduction

No.12

cyclohexanone alcohol

is

with also

borohydride upon the that

of

lithium

substituted

aluminium

the main product

(Table),

The solvent

the same order

(yield

when the

tetrahydrofuran,

reduction

of 3-methylcyclohexanone,

major

product.

steric

effect,

around

each transition

Results chlorine

This

four

solvents;

was different experiments chlorine

from that

substituent

saturated

rings,

unsubstituted group

is

cyclic of

2 3

the

with

in the sequence; observed

in the is

upon solvent of the

directing

solvation

than a-

with

of

effect

product

between

shells

of

12a-alcohol by 10-15s

substituent

axial

alcohol

in each

Preliminary show that

across

when a 3awith

those

of

of

in reactions

the monoeffect of

borohydrides.

D.S.

Noyce and D.B.

Denney,

E.L.

Eliel

Ro,

and R.S.

4 W.G. Dauben and R.E.

J.Amer.Chem.Soc.

J.Amer.Chem.Soc.

Bozak,

J.Ora.Chem.

29, &,

a,

the

or 3p-chloro-

has the general formed

a

the three

formed on reduction

in conjunction

a chlorine

the

and solvent

12-oxospirostans effect

problem.

in contrast

ratio

the methyl-ketones.

a directing

increased

for,

was formed

product

the

may be a

show that

reduction

of

noteworthy

of 4-chlorocyclohexanone

results,

proportion

is

made of this

observed

show that

increasing

hexanones

These

ratio

study

the relation

being

is

depends

being

at C can exert 3

ketone

series,

product

is

the proportion

present.

of

Further

on the borohydride

sodium

where -cis-3-methylcyclohexanol

more &-

however,

but it

acetonitrile)

has a considerable

series,

with

increasing

sizes

state.

reduced

large,

of the relative

from the reduction

to the C-methyl of

dependence

The trans-4-methyl-

is

alcohol

isopropanol,

a reflection

substituent

are not

equatorial

m,sthanol,

ketone

405

of transrcis-methyl-alcohols

effects

of

2,394

hydride.

but the proportion

solvent.

cyclohexanones

5743 (1950).

5992 (1957). 1956 (1959).

cyclo-

Reduction

406 Ratios

of

substituted

cyclohexanones

of transrcis-Substituted

the Reduction

formed

in

of Substituted.Cvclohexanones

C-Methyl cyclohexanone

Sodium borohvd,ride

Alcohols

No.12

4-Chloro cyclohexanone

3-Methyl cyclohexanone

in

methanol

82: 18

41:59

tetrahydrofuran*

83: 17

478 53

14r86

17183

propan-2-01

85: 15

37163

13187

acetonitrile’

83rll

48: 52

8x92

73827 **

55145

89rll

31:69

84: 16

33:67

Eouilibration

in

propan-2-01

Diborane

8:92

in

tetrahydrofuran

A similar,

less

when the -cis

pronounced,

effect

and -trans-isomers

of the

were each brought

to equilibrium

2-propoxide.

The same ratio

chloro-alcohols

tetrahydrofuran5

Suspension

or the usual

of

solvent,

of sodium borohydride

85-92s

chlorine

of the 4-methyl-

cyclohexanols

*

(refs.3,4)

aluminium

hvdride

observed

c&

in

tetrahydrofuran

Lithium

77-7s

in these

(refs.2,3)

substituent

was

and 4-chloro-

in the presence was obtained

propan-2-01.

c&

In the

of using

former

aluminium either solvent,

solvents.

** W.G. Dauben and R.E. Bozak, preceding reference, give a ratio of 71r29. 5 Equilibration of the chloro-alcohols occurred more quickly in tetrahydrofuran (than in propan-2-ol), and this solvent may therefore offer advantages for alkoxide-ketone interconversions in general.

Reduction

No.12 the dominant

species

to be present

expected

to be more acidic to a large

The effect &-products

groups,

one of the being

greater

with

its

smaller

reactions;

smaller alcohols

negative there

of transition

this

is

state

proportion

related

to

between carbon

than with

to

for

of

free

they may also

the

chloro-

the chloro-alcohols

can be

be present

as

interpretation

than on reduction

oxygen

oxygen and 4.12

and Cl-O related

to the

of the results,

stability

of a &-structure

atom (in

A

attraction

is because

respectively).

states

chlorine. obtained

the chloro-ketone

position)

(in m-structures)

preference

is

an axial

this

of the results,

when R equals

of

the Cl-C4

viewpoint

at the 4-position;

an increased

of a-chloro-alcohol

I

can be explained

in structures

this

in the transition

therefore

of a

to the w-chloro-alcohol.

equatorial

charge

between

the increased its

the ratio

experiments

support

from C4 (3.40

(I a)

in changing

more favourable

later,

deficient

distance

According the greatest

being

force

axial

but since

interactions

contributing

the attractive electron

the

and equilibration

be reported

factors

tendency

substituent

than in those

and the

of

chlorine

electrostatic

to

complexes

extent.

such interactions

Calculations,

407

be aluminium

than propan-2-01,

in the reduction

&-chloro-alcohol

should

in propan-2-01,

of the

by intramolecular

cyclohexanones

would be a greater

alcohols

complexes

substituted

at equilibrium

There

chloro-alcohols.

of

the oxygen

carries

of

ketone-borohydride

for

the development

The fact

that

on equilibration

suggests

that

a of the

the species

Reduction

408 present,

e.g.,

8- charge this

is in accord

differences

than

with

in isomer

hjave polar

charges

probably

being

and

gave even larger

of /+-methyl-

and l-chlorobeing

Therefore

69 and these

the bulk of the B- and 6+

of the

of &chlorocyclohexanone

gave a larger

ments

in the vicinity

reagent

respectively.

states,

reduction,

oxygen and the BH2 groups

and m).

Reduction

prssportion

I -cis ratio

being

closer

to that

lithium

than

from L+-methylcyclohexane,

for diborane

aluminium

than

of reduction

rather

than

aluminohydride

to decide

this

question.

hydride7

are required

of -cis-product

with

This may be indicative

reduction.

of aluminium

transition

(smaller

structures.

of -cis-chloro-alcohol

and dichloromethane

also

hydride

the yields

polar

for ketone

covalent

and this

No. 12

are less

states

when the reductions

were compared,

reactions

trans

essentially

by diborane,6

ratio

75% in tetrahydrofuran

II c&

are the transition

their

are reduced

cyclohexanones

(Ef.

cyclohexanones

C1C6H100A1(CCHMe2)2, at equilibrium

on oxygen)

Ketones

of substituted

anions,

The reaction

that

hydride

also the

for boro-

proceeding

by attack

but further between

experi-

&methoxy-

’ H.C. Brown, H.I. Schlesinger and A.B. Burg, J.Amer.Chem.Soc. & 673 (1939) 7 D.&S. WheNeler and J.W. Huffman, Exverientia &, 516 (19601, have suggested ‘that aluminium hydride may be theactive species in reductions of alkyl-ketones. l

Reduction

No.12 cyclohexanone 70% yield bent

8

aluminium

of &-f+-methoxycyclohexanol.

dipole

in this

and lithium

of substituted

it

exhibits

therefore

409

cyclohexanones

hydride

has been reported’

Although the same directing

to give

the methoxyl effect

group

a is a

as chlorine

reaction.

D.S. Noyce, G.L. Woo and B.R. Thomas, J.Ora.Chem.

&,

260 (1960).