The π-route to 2,4-substituted adamantanes

THE

Printed in Great Britain.

Pergamon Press.

Tetrahedron Letters No.23, pp. 1971-1974, 1970.

l?'-ROUTE TO 2,4-SUBSTITUTED ADAMANTANES

M.A. McKervey, D. Faulkner, and H. Hamill Department of Chemistry, The Queen's University, Belfast BT9 5AG (Received in UK 1 April 1970; accepted for publication 16 April 1970) During a study of adamantane rearrangements it was observed that 4-oxohomoadamantan-5one (I) (1) undergoes a smooth rearrangement exemplifies the W-route

in %

to 2,4_disubstituted

by oxidation of adamantanone

adamantanes.

dioxide in hot t-butanol, was

The product was a 1:6 mixture of (I) and 4a-

(II), m.p. 316-320°, (65% yield);

n.m.r. (loo'MHz, CDC13) -C

a mechanism which

The lactone, obtained in 96% yield

(2) with hydrogen peroxide-selenium

heated in 50% sulphuric acid at 90° for 5 hr. hydroxyadamantan-2-one

sulphuric acid e

i.r. W3r):

3400, 1720, and 1710 cm

-1

;

: 5.72 (IH, C-4), 7.35 (lH, C-3), 7.53 (lH, C-l), and 7.63-6.20 (10H).

Additional evidence for the location of the hydroxyl group was obtained by oxidation with chromic acid in acetone to the known adamantane-2,I-dione

(III) (3).

The n.m.r. spectrum of

(II) indicated the presence of a single stereoisomer and this was confirmed by capillary g.1.p.c. analysis of the corresponding trifluoroacetate. follows.

The configuration at C-4 was assigned as

Reduction of (II) with lithium aluminium hydride gave two dials (ratio 19:l).

The

n.m.r. spectrum of the major diol contained a single low field absorption for the protons on C-2 and C-4 suggesting that this product was one of the two possible symmetrical adamantane-2,4dials (IV) and (V), and the i.r. spectrum (4.10D3M CC14) exhibited a strong absorption at 3540 cm

-1

due to intramolecular hydrogen bonding.

has the correct configuration the hydroxy-ketone (IV), respectively,

Of the two diols (IV) and (V) only the former

for intramolecular hydrogen bonding.

It follows, therefore, that

and its major reduction product have the configurations shown in (II) and Reduction of adamantane-2,I-dione

with lithium aluminium hydride gave ali

three adamantane diols in yields of 45% (IV) 16% (VI, and 39% (VI).

1971

1Y72

NO.,?j

&I A? R ’

OH

0

0

OH

OH&H

@OH

OH

OH

(ml

(a)

(E) c;OCl

CN

IQ (IQ 8 0

OMs

I@)

(VIII)

O

Cl

1x1

(ij,

methanesulphonic

adamantan-Z-one prepared by

These authors found that treatment of adamantanone with sodium azide in acid gave 4-methylsulphonyloxyadamantan-Z-one

and the suggestion was made that

the product results from a direct substitution reaction on adamantanone. configuration

(jgi,

1-1

We can now comment on the configuration of the 4-substituted Sasaki et al. (4).

8 /

at C-4 was not established,

into bicyclo[3.3.l]non-2-ene-7-carboxylic

Although the

the observation that the product could be converted acid (VII) (1) on treatment with potassium hydroxide

suggests that the mesylate group is equatorial as in (VIII) since this is exactly the configuration which permits fragmentation of the adamantane skeleton. spectral data for 4a-methylsulphonyloxyadamantan-2-one chloride, now show this to be the case

:

The physical and

(IX), obtained from (II) and the acid

mesylate (IX), m.p. 106-107°, was distinctly

different from mesylate (VIII), m.p. 73-75O. The rearrangement of (I) into (II) is reversible in 50% sulphuric acid and the mechanism, which can be interpreted as shown in the scheme, illustrates the v-route substituted adamantanes.

50% sulphuric acid.

to

Acid (VII) also gave (I) and (II) in the ratio 1:G when treated with

In 80% sulphuric acid, with added carbon tetrachloride, the rearrangement

of (I) gave 4a -chloroadamantan-Z-one

(X), m.p. 207-209°, in 58% yield.

(X) was also produced

when the acid chloride (XI), obtained from (VII) and oxalyl chloride, was treated with boron trifluoride etherate in diglyme.

1973

NO.23

In fact the conversion of adamantanone into the keto-mesylate of the r-route

(VIII) is also an example

to substituted adsmantanes and is not a direct substitution reaction as was

suggested by Sasaki et al. (4). Korsloot and Keiser (5) reached this conclusion as a result of their study of the Beckman" rearrangement of adamantanone oxime in 96% sulphuric acid, a reaction which proceeds by ring fission and recyclisation giving (II) and its equatorial isomer, and we have obtained direct evidence on this point. azide in methanesulphonic

Treatment of adamantanone with sodium

acid at O" for 14 minutes afforded, in additton to (VIII), 15% of the

unsaturated nitrile (XII) (5). treatment with methanesulphonic

This compound is an internediate in the reaction since further acid alone produced (VIII) in high yield.

(VIII) is, therefore, an example of a Schmidt fragmentation-cyclisation direct substitution reaction with the ketone.

Nevertheless,

The formation of

reaction and is not a

it is possible to effect such a

reaction with adamantanone although the conditions required contrast greatly with those necessary for a similar reaction with adamantane. l-bromoadsmantane

Conditions under which the hydrocarbon gives With aluminium bromide catalysis,

in high yield leave the ketone unchanged.

however, and a reaction time of 10 days, bromination does occur giving 5-bromoadamantan-2-one (XIII) (6) in 90% yield.

A second product (2%) was identified as 6-bromoadamantan-Z-one

(XIV),

m.p. 187-189'. on the basis of the spectral data and on conversion -via 6-hydroxyadsmantan-2-one (XV) into adamsntane-2,6-dione

(XVI) (7).

F”2cH3

0

J? 0

(xrll) OH

4

(EJii)

(m

(XVI)

No.23

1974

Finally

we wish Exposure

adamantanes. (XVII)

of saturated

and (XXI)

(12H,

(14%),

ml.

and 1710 cm

Wolff-Kishner

hydride

reduction

of steric

preponderance addition

formation alcohol

reduction

of (XXII) approach

of (XX),in acid

equatorial

of the formates

9.09

:

reaction

products

(VIII)

(VII) in 50% sulphuric

gave

(3H,s),

was determined a single

the axial

The dichotomy

mesylate

the diene

(XXII),

8.76

(3H,s),

configuration

can reasonably

from

acid,

m.p.

cation

with

requires

143-144O

(8).

aluminium which

on the grounds

preferentially

the earlier

(XII) in methanesulphonic

still

174-175O;

Similarly,

(xX1).

occurs

m.p.

and 7.48-8.55

194-196O,

be explained

and a

(XX) (86%)

Lithium

as follows.

alcohol,

of behaviour

m.p.

ester

(X1X)(1%)

the alcohols

gave 2,2_dimethyladamantane,

to the 4,4-dimethyl-2-adamantyl side.

from the unsaturated

acid for 2 hr. gave

(CDC13)Z

assigned

the cyclised

prepared

56.5-58O,

in high yield

was

to 2,4_trisubstituted

gave 4,4-dimethyladamanta-2-one

of (XXII)

afforded

control

of the equatorial (II) from

n.m.r.

of the cyclisation

of formic

less hindered

;

of the v-route

Hydrolysis

oxidation

-1

m.p.

to hot formic

(8%).

and subsequent

1720

(KBr):

the extension (XVIII),

iodide,

formates

The stereochemistry

basis

of alcohol

and methylmagnesium

mixture

i.r.

to illustrate

on the the that

from the

cyclisations,

acid and the axial

an explanation

(9) (10).

References (1)

A.C. Udding,

(2)

H.W. Geluk

J. Strating,

(3)

A.C. Udding, J. Strating, and H. Wynberg, Tetrahedron Letters, 1345 (1968); we thank Professor Wynberg for providing us with the spectral data for adamantane-2,4-dione.

(4)

T. Sasaki,

(5)

J.G.

(6)

H.W. Geluk

(7)

O.W.

and J.L.M.A.

E. Eguchi,

Korsloot

and T. Toru,

and V.G. Keizer,

and J.L.M.A.

Webster

and H. Wynberg,

Schlatmann,

(8)

C.W. Woodworth,

(9)

All new compounds

V. Buss,

(10)

We thank

gave

the Northern

J. Amer.

Tetrahedron

Schlatmann,

and L.H. Sommer,

Tetrahedron

Tetrahedron, -

Ireland

analytical

Ministry

3517

24,

Chem., 2,

and P. van R. Schleyer,

satisfactory

5361

5369

(1968).

3390

(1969).

(1969). (1968).

3103

(1964).

Chem.

Comm.,

and spectral

of Education

5719

(1968).

Chem. Sot., 91, Letters,

Tetrahedron,

J. Org.

Letters,

2,

569

i.e.

(1968).

values.

for a postgraduate

grant

to D.F.