Functionalisation of unactivated methyl groups through cyclopalladation reactions

Tctmk&m Vol. 41, No. 4, pp. 699 to 711.1985 Printed in Cm1 Britain.

Llluc4020/85 Pcrw

s3.00+ h

FUNCTIONALISATION OF UNACTIVATED METHYLGROUPSTHROUGH CYCLOPALLADATION REACTIONS JACK E. BALDWIN.*RICHARD H. JONES, CARMENNAJERA,’ ANDMIGUELYUS’

Dyson Perrins

Laboratory,

UnivWSity

of

Oxford,

South Parks Road, Oxford OX1 3Qy, U.K.

(Received in UK 26 November 1984) Abstract - The transformation of the organopalladium compound (3) into the corresponding deuterlated, chlorinated, or oxidized derivatives (71, (8). or (9), (111, and (12) respectively, is described. The palladatlon of compound (9) takes place regloselectively leading to the palladated system (13). which is transformed into the difunctionallsed oximes (15) and (16). The palladation of E-2,2-dimethyl and 2,2.6,6-tetramethyl-cyclohexanone oxime leads to the corFespondlng organopalladium compounds (17) and (27). which through deuteriation or oxidation affords the expected products (21) and (31), or (221, (231, The second palladation of the compound (22) (241, and (32), respectively. takes place on the remaining methyl group yielding the organopalladium Finally, E-lupanone oxime is palladated selectively in the derivative (26). 23-position leading to the organopalladium compound (38); the transformation Of this compound into its 23-deuterio and 23-acetoxyderivatives (41) and (42), The stereochemistry in the palladation oP respectively is also described. lupanone oxime is deduced Prom NOE studies at 500 MHZ. Introduction o-Organopalladium

compounds are very versatile

one oP the most important If

the

o-organopalladium

palladium

atom it

reaction

being

intermediate

decomposes

HX

through

+

in organic

syntheses

the palladium(I1)

assisted

bears

a hydrogen

nucleophillc

atom at the R-position

a ‘PdHX’ B-ellminatlon

processes,’

attack

+

A

Nu

scheme However, species,

o-organopalladium for

compounds lacking

example the products

cl).’

(21.’

g-hydrogen or

(3).”

atoms are usually

on olefins.

with respect

(Scheme).

[WHX]

W(0) -

and in catalytic

quite

stable

to the

.oo

Ltd.

J. E. BALDWIN et al.

700 We were interested substituted

in the possible

cyclic

applications

oximes oP the type

(3)

of organopalladium

in order

compounds derived

to Punctionallise

unactivated

Prom

methyl

groups.‘*’

RESULTSAND DISCUSSION Functionalisation the reaction led

oP E-pinacolone

to the dimeric

oxime with disodium

organopalladium

monomeric complexes When the diner

(4)

(3)

and (5)

(6)

compound (3),

by treatment

was treated

successively

pyridlne

complex

analysis

and in the monomeric complexes

The reactivity Punctionallse

uas obtained

methanol-tetrahydroiuran

Thus,

solution*

chloride

Pollowed

exchange

and product

in other

solvents,

The oxidation

by reduction (8) e.g.

which could

with pyridine

by i.r.

toward ditierent

the reduction

of

organopalladlum

reagents

was isolated

(64% overall

mixtures

of oxidized

and halogenated

(@ R=H, X=CI

in

tetra-

palladium-chlorine was carried

products

m-chloroperbenzoic

(7) R=H, X=0

to The

in carbon

to the expected

products.’

(31 R=H, X=/i

out

were observed.

acid,”

or lead

HoweYer. when oxidation

(9) R=H, X=OCOCHS (10) R=H, X=OH

(6) R=CH,CO, X= Py

(Ill

0

in 41% yield.

decomposition

(4) R=H, X=Py (5) R=H,X=PPh3

(7)

When the chlorination only

oP compound (3) with t&bromoaucclnlmide’O.

afforded

in order

with chlorine

led

yield).

or dichloromethane,

data.’

with sodium cyanoborodeuteride

product

compound (3)

the new O-acetylated

in (3) was deduced by X-ray was studied

compound (3)

the corresponding respectively.

and pyrldine

and ‘H n.m.r.

with sodium cyanoborohydride’

water-dioxan

into

or triphenylphosphine,

The stereochemistry

and (5)

work oP Shaw -et al’ in ethanol

acetate

be translormed

anhydride

aPPorded the deuteriated

oP the same starting

tetraacetate”

(4)

Fromthe previoua

tetrachloropalladate-sodium

with acetic

in 901 yield.

OP the compound (3)

the C-Pd bond.

chlorination

Compound (3).

oP the Organopalladlua

R=CH,CO, X=OCOCH,

OCOCH,,

/x

02) HO,

N

X' X2

03) x=/2 (14) X=PPhS

(Xi) x’=D, X2= OCOCHl (16) x’= x2= OCOCH~

was periormed

compound (9) Hydrolysis hydroxy

on the pyrldine was isolated,

ot the acetoxyoxime

derivative

(10)

complex

aiter

(4)

reduction (9)

oxidation

with potassium

in 35% yield.

proceded

smoothly

with sodium borohydride’. hydroxide-ethanol

with lead in “. led

tetraacetate

quantitatiye

and

yield.

to the corresponding

Functionalisation of unsaivated methyl groups The oxidation

can be also

Thus, when compound (3) the expected

borohydride’

in overall the lead

bonds with lead

tetraacetate

oxidation

(12)

was carried

complex’

was observed.

a product this

carbonylatlon

we attempted

decomposition

palladatlon

lithium,

palladatlon

complex

via

since

the dlmerlc

of

(9)

takes

organopalladium

(14)

sequences

respectively

Preparation

and Reactivity

The palladatlon

organopalladlum of

Reduction

case

than two hours some over

Palladated

of

However,

and subsequent

in our hands only

(22)

(18)

by X-ray

(24).

Thus,

with palladium

occurs

process

methyl group’*

pyrldlne

compound (17)

exclusively

afforded

by reduction tetraacetate

prior

(18) The

to formation

yield. was

on the reaction

per qol of the -in situ with sodium borohydrlde,9

led

per mol of the --in situ (24) was isolated in 581 yield.

acetoxyketone since

dlmerlc

the complexes

and (21)

depending

if

(25)

can be easily

complex

the reflux

time was longer

was obtained

transformed

of

as the corresponding

with lead

into

as by-product. (24)

by catalytic

in carbon

tetraacetate

(1:l

product

in 791 yield.

the second

palladatlon

with the palladium trlphenylphosphlne reactions

The palladatlon

organopalladlum

(23)

tetrachlorlde

Prom a-chlorination

and subseqeunt

ox1me.l’

the corresponding

(20)

led to the expected

and also

the product

the palladatlon

2,2,6,6-tetramethylcyclohexanone

to Pd-D exchange

ketone

Cyclohexanone

respectively.

in 68% overall

yielded,

followed

into

Acetylation

(20)

one mol of oxidant

with chlorine

the reglochemlstry

isolated

Next we studled

led

a,@-unsaturated

with sodium borohydrlde’

afforded

the

reduction

to the corresponding

crystallography.

using

the mixture

led

951 and 99% yield,

must be controlled

compounds Prom Pd-Cl exchange

We have studied

the

into

on charcoal.

of c-acetylated of

into

described

was transformed

derivative

the corresponding

conditions

(25)

atom.

methyl groups

and 2,2,6,6_Tetrametyl-

substance

When two mol of lead

was employed

to

of

carbon

was transformed

by the previously

oxlme ”

tetraacetate

the oxidation,

some of the corresponding

by reduction

amd (16)

2,2-DlmethylThis

with lead

or (18)

the reglochemlstry

which was transformed

compound (13)

or triphenylphosphineln

in 961 yield.

The chlorination

conditions

naphthalenlde yielding

and

structure

was not observed.

on one of the remalnlng

in 83% yield,

(15)

the g-acetylated

the reaction

The oxidation

this

to palladium(O)

the C-Pd bond.

out to establish

The organopalladium

was determined

complex

oxidation

hydrogenation

chlorinated

led

CO

in 9811 and 86% yield.

Oxidation

(22)

complex last

followed

When the

unstable

be bonded to a methyl or a methylene

with sodium cyanoborodeuterlde

products

to acetoxyoxime

If

(18)

(17)

pyrldlne

generated

out in the

the acetylated

The exact

activate

Palled,

(4)

conditions.

CO insertion

or lithium

exclusively

in 851 yield.

complex afforded of

stolchlometry,

In this

reaction ethanol

compounds,

was carried

complex

oxlme.”

to usefully

of E-2,2-dlmethylcyclohexanone

in 89s yield.

generated

carbonyl

the corresponding

the expected

was carried

compound (13)

with pyrldlne

complex

the pyrldlne

isolated

with sodium

the C-Pd and C-NOH

oxidation

dlmerlc

metal,

could

derivatives of

compound (17)

by treatment

structure

of

or benzaldehyde)

place

in 715 yield.

or oxldation

of

(6).

and lead

reduction

of

pyridlne

out in refluxlng

Pd-Ll

compound (9)

or acetoxy

and (19)

described

oxidized

lithium

iodide

oxidation

under different

in any case,

the palladium

deuterlo

.

carried

but,

(methyl

corresponding

Oxlmes

pyridlne, after

the corresponding

generated

the formation

the transmetallation

with butyl

metallation

We Pound that phosphlne

complex

products.

A two stage

yielding

toluene

to be the corresponding

with electrophlles

the second

of compound (3)

The same reaction

the transmetallatlon treatment

the --in situ in 641 overall yield.

has not been determined

Finally,

anhydride,

the simultaneous

per qol of

out in refluxlng

which appears

product

pyridlne

was isolated

gives

of oxlmes”

Thus, when the previously

was obtained

attempted

reaction

with acetic oxlme (11)

we attempted

tetraacetate.

ketone

We also

acetoxy

g-acetylated

831 yield.

of two mol of oxidant

hydroxy

treated

0-acetylated

when they are not too hindered,” presence

out on the protected

was successively

tetraacetate Since

carried

701

of

led

to a mixture

of

the oxlme.

on compound (22)

and Pound that

atom bonded to the remaining complex

(26)

(821 yield).

of a very hindered of this

dlmer (27)

molar ratio)

ketone

oxlme,

oxlme under the standard in 86% yield,

which upon treatment

702

J. E.

BALDWINet al.

(17) R=H, X=&

{2l) R=H, X=0

(18) R=H, X= Py

&I) R=H, X=OCOCHI

(19) R=H,X=PPha

(29 Ft=CH,CO, X=OCOCn,

(20 R=CH&O.

X= Py

I

-w-x R4rF

R”bJx

e

6

(27) R=H, X=/,

C3D R=H,X=D

(M

(~~R=CH&O,X=OCOCH,

R=H. X=Py

(29) R=H. X=PPh, (=$ R=CH,CO,x=Py

with pyrldlne or triphenylphospine

Acetylation

in ~a. 100s and 901 yield.

pyridine yielded the g-acetylated The deuterfation oxidation and

led to the corresponding complexes (28) and (291, respectively of (27) with acetic

anhydrlde and subsequent treatment with

pyrldlne complex (30) (915 yield).

of compound (27) led to the expected

product

(31) (6&l yield).

of (27) through the --in situ generated pyridlne complex (28) alforded

f&acetoxy oximes in good yield

(9%

$&. 1:l molar ratio)

Houever ,

a mixture

arising from isomerlsation

To avoid this problem we protected first

of

both

z-

of the

the oxime

oxlme group under the reaction

conditions.

group of (29) by acetylation.

Then, the oxidation of the pyridine complex (30) with lead tetra-

acetate followed by reduction with sodium borohydrfde led to the expected product (32) (83s yleldf. Attempts at chlorination intractable

of (27) with chlorine

in carbOn tetrachlorlde

yielded only an

mixture of reaotion products.

Finally,

ye studied the palladation

dfmethylcyclopentanone,” unsuccessful

f-)-earvone,ao

of oxlmes derived from 2-methylcyclohexanone,‘* (-)-f’enchone,

*’ and (+)-csmphor.*a

and either the corresponding oxlme complexes or intractable

2.2-

These reactions

Were

mixturea were

obtained.‘**’ Preparation and Reactivity from lupenyl acetate yield),” finally

(33).‘*

of Palladated LupanOneOXime. E-Lupanone oxime (37) was prepared

which was successively

hydrolyzed to lupanol (35) (862 yield),** treated with hydroxylamine hydrochloride

hydrogenated to lupanyl acetate oxidized“

1891).

(34) (Ca. 100s to lupanone (36) (861 yield),” and

Functionalisation The palladatlon dimeric

of g-lupenone

OrganopalladlrrP

equatorial

methyl

pyrldine

(23-1.X,)

was confirmed

the

in situ

oxime

generated

with

the

(41)

pyrldine

in situ

(38)

wlth

monomeric

complex

(39)

sodium

Y’=

(@

Y’=H, &OCOC%:

at

uafi unsuccessful, complex

method

led

(39)

to the expected

took place

5OCUHz.”

at

The dimeric

and (40)

by

compound

treatment

led

(38)

with

to the lead

with

corresponding

tetraacetate

through

but when the same reaction of

the

100% yield.

cyanoborohydride of

703

palladatlon

complexes

Oxidation

pyrldine

H, B-OCOCWs;

(33)

the

in 97% and ~a.

in 911 yleld.

formed g-acetyl

described

That

by HOE studies

respectively,

of campound

methyl groups

by the above

In 761 yield.

corresponding

or triphenylphosphine,

23-deuteriolupanone out

(38)

into

The reduction

(37)

compound

group

was transformed

(38)

oxlme

of unactivatal

(38)

successive

(i

X=L

oxidation

the

uaa carried with

lead

Y2=CH2

YeH.CH,

(35) Y’=H. lbOH;Y’=H,CH,

(39) X= Py

(~6) 60;

(m) X=PPtl,

Y~=H,CH~

(37) V’=E_-NOH;Y2=H,CH,

($1)R=H.X=D @2)R=CH&O, tetraacetate

and reduction

in 901 yield. palladium

dlmer

agreement

with

(38).

oxlme and the

cornPent.

of

All

borohydride (41)

and

led

to the

(42) was based data

for

the

expected on that

23-aoetoxy determined

lupanone

derivative

(42)

of the organo-

derivative8

were also

in

sterecchemletry.

Considerations.

in lupanone

(23-w,)

cyclohexanone deserve

sodium

The ‘If, ‘Ii, and “C n.m.r.

the assigned

Stereoelectronic group

with

The stereoohemlstry

X=OCOCH2

0Ame. course

of these

The exclusive the

course

of the

resulta

of the

two-stage

functionalisatlon two-stage palladation

can be explained

by the

palladation sequence operatlon

of the

equatorial

sequence

on pinacolone of

methyl

on 2.2-dimethyl-

two effects:-

oxime

704 (1)

J. E. BALDWINet cf. Cyclopalladation

“target”

is facilitated

methyl group.

closest

approach

This

by a coplanar perhaps

is

arrangement

unexceptional

between the oxime-coordinated

since

palladium

of it

the oxime and the

is

the geometry giving

and the methyl hydrogens;

as in

(43).

Figure 1

This geometry

is

cyclohexanone

oxime.

suitable

achieved

substrates

double

this

complex

reaction,

of

this

explain3

bearing

why cyclopentanone The crystal

show3 the expected methyl group

substituted oximes were not

structure

of

the

near-coplanarity

, confirming

of the oxime

in the product

the general

effect.

The operation

even in the case E-substituents

also

methyl group in a P-methyl

vide ~upra.

(181, fig.1,

bond and the palladium

validity (2)

This requirement for

monomeric pyridine

by the equatorial

of A(**‘)

strain

of pinacolone

being

axial.

”

in 2-disubstituted

oximes

, will

result

Thus compound (221,

cyclohexanone

in a preference the substrate

for

oximes,

for

and perhaps

the larger

a second

stage

of

the

of

HQ :

HO- --

cyclopalladation. funotlonalisation methyl

group.

will

prefer

will

occur,

as vas indeed

conformation

(45)

from consideration

over (1)

(44).

Consequently,

the second

above,

at the unfunctionalised

observed. EXPERIMENTAL

General.apparatus. were recorded

i4.p.s

1.r.

are uncorrected

spectra

vere

and Were measured on a Buchi-Tottoli

determined

in a Bruker Wi 300;

‘H,

“C.

with a Perkin-Elmer and “P

n.m.r.

capillary

257 spectrometer.

spectra

melting-point

‘H n.m.r.

spectra

were measured in a Bruker AH

Functionalisation of unactivated methyl groups The NOE studies

250. n.m.r.

were carried

were performed

phosphoric

acid.

kllcroanalyses available

were performed

purification.

Dlsodium

Palladatlon A solution solvent crude

g-lupanone

palladated

of Compounds (131,

oxlme,

8.4 Hz. CH,Pd), CH,CN),

20.93

170.58

3.96, (g,

C-0).

(3.

Compound (17), (C-N);

CHIC), 1.87

4.01

cH,CO),

m.p.

22.23

6H 1.29

(3 H,

3.05

(CH,),CCNl,

26.48

(3 H, s.

(dec.)

cellte.

CH,),

(methanol)

1.42-1.92

39.65

oxlme,”

further

2,2.6,6-

derivatives

(3).

-and (38). General Procedure.(1.2 mmol). and the for -ca. 3 d. The in dlchloromethane

was dissolved

The solvent

v(CC1.1

33.67

(br t,

was evaporated

3360 (OH). (3 H,

B,

1740 (C-01,

to give

the

and 1655 cm-’

CH,CO). 2.34,

(lH,

CH,Pd),

(t,

(Found:

N, 4.96;

H, 5.00;

2.63

(2 H, 2 d, J

br B, OH); 6C 12.75

52.90

(s.

CCH,),

C, 34.6:

Cl,

H. 5.1;

12.57);

N, 5.1;

v(Nujo1)

68.84

(9.

(t,

CH,O).

(1 H. br B, OH): 6C 21.76,

LJH,CN), 40.40

(br t,

CH,Pd),

2.57

24.01,

49.47

Cl,

12.6.

3440 (OH). and 1650 cm-’

C7 H, m, (CH,),CCN and CHaxCNI, 2.51,

m, CHeqCN), and 8.15

(q,

comnerclally without

used

at room temperature

CH,CN). 2.16

m/e 562 (M+ for “Cl and “‘Pd). -Compound (271, q.p. 177-170°C (dec.1 (hexane) (B,

reagents

C-N).

(B,

C, 34.07; CH,),

B,

(lH,

or to

by recrystallization.

(q. cH,CC),

ppm

182-1850C

requires

Hz. CH,Pd).

(271,

(2 H, 2 d. J 11.3 Hz, CH,O), and 8.27

and 173.11

C,.HI,C1,N,O,Pd,

through

Yhlch was purified

B,

(171,

(15 mmHg), the residue

135-138OC (hexane-chloroform);

6H 1.18 (3 H,

(C-N);

All

grade and

best

Bodlum acetate

(10 ml) was stirred

filtered

and “P

procedures.

mmol),

pressure

“C,

ZAB 1P and l6F instruments.

laboratory. the

‘H,

to the solvent

and the organo-palladium

Isolation

(1 mmol) in ethanol

m.p.

oxlme,”

tetrachloropalladate,(1.2

and the solution

Compound (13,

this

to the literature

was removed under reduced

(3 x 20 ml),

of

All

are referred

with VC Micromass

according

of Oxlmes.

oxlme

shifts

M _E-2,2-dlmethylcyclohexanone

tetrachloropalladate, oxlme,”

of disodlum

corresponding

were determined

by Dr. F. 8. Strauss

were prepared

and (5)’

chemical

Johnson Matthey or Sigma) were of

BDH,

tetramethylcyclohexanone (41,

in a Bruker AM 500 instrument.”

in deuterlochlorofonn:

Mass spectra

(Aldrich,

out

705

(2 H, 2 d, J 8.2

24.47

13 t,

CCH,),

(3,

and 176.71

PPm

C-N);

requires

C, 38.73:

H, 5.85:

CH,CCRd), 1.29-1.69 J 7.1 Hz, CH,Pd). 31.04

(3 q.

and 8.42

m.p.

requires

C, 61.85;

(3 H, s.

28-CH,),

27-CH,),

0.95-1.94

CHI, 2.03

(12 H, m with

3 x CH,),

Compound (381,

H, 8.65;

Preparation

(281,

of

Pyridine ml,

N, 4.6.

B

at 1.05

Complexes

40.10

(br t,

C, 61.1;

1.0,

(25-CH,)

H, 8.6;

CHCl,);

(br t.

(181,

and 1.26

CHPd). 2.61

(28). (271,

23-CH,Pd)

was stirred

recrystallized

to afford

C,oH,,C1,N,O,Pdl 6H 1.24 2.33,

(CH,),l,

v(CC1.j

0.93

(24-CH,).

28.09, C-N).

ppu~ (B,

C,,H,,,Cl,N,O,Pd, (OH); 6H 0.76

(6 H, 2 8, 26- and

2 x CH,, 9 x CH,, and 6 x

(1H. d, J 7.5 Hz. CHPd), 2.98 General

ppm

Procedurb.-

10 min.

To a solution

m. of

(5 ml) was

The solvent

the corresponding

(lH,

C-N).

(B,

mmol) in tetrahydrofuran for

B,

(2 H, 2 d.

25.51,

3360 cm-’

D.91,

(3 H,

2.46

and 179.61 N, 2.4.

and 177.69

-and (39). or (38) (0.1

0.2 rnmol) and the mixture

C3 t,

CH,Pd),

Hz. 29- and 30-CH,),

(1 H, br signal,

compound (17).

36.46, 41.22

-31.g”(c

(C-N);

was

complexes

(181,

and (39). (Py);

m.p.

6H 1.27

21.96,

24.10,

CCH,),

124.98.

Complex (281, (CH,),

2

H. 6.2;

2 x CH, and 3 x CH,),

(Found:

Caky

(1 H. br B, OH); 6C 43.15

(0.02

8.6 Hz, CH,Pd).

cm-’

2.50

(15 mmHg) and the residue

Complex (18), cm-’

OH); 6C 17.74.

(6 H, 2 d, 26.8

C30 H, m with

organopalladium

added pyrldine

B,

(2 B. 2 x CCH,).

N. 2.40);

0.84

C, 38.9;

at 1.37 and 1.49,

B

>21OoC (hexane-chloroform)

(1 H, m. CH,,CN),

the dlmerlc

51.19

(Found:

w(CHC1,) 3370 (OH) and 1630 cm-’

2

(1 H, br

39.10,

0.77,

CHeqCN), and 8.14

evaporated

N, 4.52):

(Py);

138-140°C (3 H. s,

3.08 24.51

(lH, C3 t.

137.66, m.p.

6H 1.25

and 2 x CH,],

(hexane-chloroform); CH,),

(CH,),],

170°C (dec.1 1.91

B.

26.89

(3 d, Py),

w(CHC1,) 3230,

(q.

7.78,

8.68

CH,),

and 176.77

(hexane-chloroform);

CH,CCPd),

3140 (OH),

(7 H. m. 3 x CH, and CH,,CN),

q , CHeqCN). 7.34,

152.49

(3 H,

1.45-1.92

1.30-1.72

(5 H. 3 q, Py),

40.58

(t,

ppm (s. v(CCl.1

CH,CN),

1640 (C-N).

2.11,

and 9.93 44.35

(t.

2.47 (1 H,

CHIPd),

B.

OH); 6C

48.76

(B,

C-N). 3330,

3120 (OH). 1635 (C-N).

Cl2 H, m with s at 1.40 and d at 1.49,

(1H. d, J 7.5 Hz, CHPd), 2.42

and 1600

(2 H, 2 d, J

and 1610

J 1.3 Hz,

(1 H. dd. 2 7.5 and 1.4 Hz. CHPd). 7.33.

J. E. BALDWIN er al.

706

7.78,

8.67

28.13,

(5 H, 3m, Py),

31.46

(3 d,

Py).

Complex (OH),

(3q, and

(39). 3080.

30-CH,), 1.26

179.43

0.93,

0.94

(24-CH,),

CH,,CN), 8.92

OH);

Preparation

of

(29).

above

described

Complex 1570 p

or

10.2

and JHp 4.2 CH,O),

12.60

(q.

cH,CN).

128.37 Hz,

m.p.

C,,H,,ClNOPPd cm-’

(Ph); 3

Hz, 7.67

X

CH,

(15

h,

ring),

2 m, 3 x Ph),

Cl,, and

(q,

130.41

(d,

(dd,

.&p

134.40

1585

(26),

cm-’

(Ph); (5

CH,~CN),

3.81.

10.67

gH,CN),

(d,

CH,+

Complex

4.28

(2 h,

mol)

(14), it

was

1600,

1.69

3.97

Hz,

CCH,).

Hz, CL,,

and

(1 H, dd.

(2 H, 2 d,

2.6

(s,

N, 2.6:

2 m with

Hz,

(C-N),

OH);

6C

70.23

134.39

(t.

(dd,

Jcp

ppm.

P,

H,

3.76,

JCp 49.4

(8

OH);

175.17

an

The

as

CHPd),

d,&P

52.48

6.51;

d,

10.0

(0.1

owplexes

1640

Hz,

(lH,

H, 5.4;

(lH,

and

5.69:

CHPd),

CH,Pd),

49.15

Hz,

Ck),

130.41

(s.

C-N);

6p 30.94

Cl,

CHp).

(OH) and 3090 and&P

(3

128.26

t,

(dd,

131.11

(d,

508

W!+ -35,

ppm; $2

7.4

m, CHeqCN),

24.44

CCH,),

5.6.

29.6

(1H.

23.75,

(s,

P,

3130 1.33,

3.12-3.25

(d,

6.5;

u(NuJol) dd at

bC 22.07.

(t.

6P 30.49 (29).

(1 H,

7.40,

3 x CH,

Jcp

Jcp

10.0

48.8 for

HZ, “Cl

Complex

30-CH,), 1.27,

(9.

(9,

L 10.2

and JHP 7.0

at

cH,C),

CCN),

CL),

2.05,

(dd,

(t,

24.09.

12.0

(C-O), Hz,

1670

(C-N).

(15

24.47

128.31

Hz,

H. 2 m,

(3

(dd,

t, tip

170.63,

Ch),

1600,

3 x CH, ring

CHPh, CHaxCN, and CH,CO.

CH,O)

ap

1725

7.62-7.81

21.98,

68.29

134.40

(15

H, m with

7.35-7.50,

40.56

(3 t.

(t,

(dd,

7.60-7.75

11.7

128.29 Hz.

(C-N)! H.

Hz (24-CH,).

CHPd and CH,,CN).

q

6H 0.74

3 x CH,. 3.12

9

x

0.88,

CH,,

(1 H, q ,

6

&p

28.30, 10.8

(26-

Hz, (8,

-4.05O(c

CH,

cm-’

and

(Ph);

1.43,

and

and CHPd),

3.22

(1 H, m,

3 x Ph),

and

3 x CH, ring),

36.62

10.7

Hz,

130.53

and

171.46

Ck).

(2 8.

C-O

Cb),

1.48, 0.76,

2.00-2.20

lo.71

(3 q. 130.38

6p 30.75

CHCl,);

0.84

and 27-CH,),

and CHPd].

and

32.42

C-N);

6H 1.17

(6H, and

(1 H. dd.

3 x CH, an 3 x CH, ring),

H, 2 q , 3 x Ph).

177.76

28-CH,),

0.99 X

1.33,

25.39,

and

[air (3 H, 9,

3 s at

with

(15

(dd.

CHP),

(OH) and 3040

1.28,

3 x CH, ring),

CH,Pd),

Jcp

3120

3 s at

(hexane-ohloroform);

cm-’ [37

v(NuJo1)

(ethanol);

49.39

134.40

1665

0.88-1.95

1.40,

(OH),

Hz, CH,O), 7.35-7.53,

6C 21.03

Hz,

CHPI),

m.p.>210°C

and

JI 3.3 Hz,

2 x~CH,),

(40).

(Ph),

J lo.8

1.25-1.63 Hz.

Cl),

dd at

Hz, and s

52.87

192-193°C

CHPd).

38.24,

Hz,

m with E 10.2

v 3200

ppm.

18.16,

(2 s, 48.3

2 d,

50.8

d, J 8.8

6c

1.87.

CH*Pd), Jcp

m.p.

Hz.

OH):

50.77

(d,

(acetone-hexane);

(7H,

at

3. 0 HZ, OH); (t,

130.94

8.8

.php

8.5

57.4;

Hz.

Jcp

(38)

prepared

(C-0).

CH,CO).

(d,

6P 30.37

Cl,

JHP 2.4

CHPd and

30 min. the

dimer

CH,Pd),

130.86

1.76-2.02

47.76

Hz.

Oeneral or

afford

1730

(t,

40.47

C,

(40).

for

and JHp 3.4

(3 H, s,

(1 H, d. J 9.6

(d,

Ch),

2.05

N. 2.57;

cH,CN),

(dec)

6H 1.21-1.75

H, m with d

42.30

and C-N)8

3050

Hz,

156-158OC

(1 H. d, &p

(t,

Jcp

11.4

(OH),

10.2

2.06

lo.46 (t,

to

CHIC),

1.20-1.62,

CHp), 131.11

m.p.

1.82-2.11

2.11

and

40.77

J

CHp),

and

and

(5 H, 3 m. Py),

(27).

was refluxed

and 10.63

(d,

-and

(17).

2m, 3 x Ph),

(Pound:

H. 5.37;

(29).

corresponding

3150

dd.

29-

(25-CH,)

J 8.5

8.67

3165

Hz,

(26).

3210,

H,

1.07

2.11,

7.78,

(13).

ml)

the

u(CC1,) 2 6.8

“‘Pd).

Complex

Hz.

CH,),

(26).

(20

C-O and C-N);

(ethanol)

CH,).

(19).

CH,CN),

H,

130.60

CHPd, and CH,,CN,

ring,

152.64

C-N).

aompoond

complex

(1

(q,

(2 8,

C, 57.37;

(3 H. s,

(15

Ck),

171.29

ppm (s,

d at

7.34,

(26)

1.56

23.40

2 s at

was recrystallized

(3 H, s,

cH,CO)

and

25.40, 137.60,

CHCl,);

H, m with

complex the

1.8,

(6 H, 2 d,

residue

w(CHC1,)

CHIC),

1.95

ll.OHz,

requires

27.71

Hz, Ca,,

(q,

RX,),], 124.97,

0.85

92 H, m with

(14).

into

(ethanol);

196OC (dec.)

6H 1.17

situ

[30

in methanol

the

7.62-7.76

20.89

170.60,

(19).

of in

CHPd),

Jcp

mol)

0.77,

2.00-2.17

and 177.69

and the

case

(3 H, s,

Hz.

C3 t,

CH,Pd),

-30.47°(c

Cal’; 28-M,),

organopalladium

0.2

ImHg)

7.37-7.52,

(dd.

CH,),

Ccmplex

g,

130-132°C

6H 1.06

40.19 (t,

(1 H. m, CHeqCN).

Complexes

dimeric

In the

m.p.

(Ph);

Hz,

12.7

(15

37.60, 45.32

0.98-1.97

3.04

23-CH,Pd),

(0.053

(40).

$1.0

CH,O),

CHPd).

was transformed

(14).

cm-l

(t,

27-CH,),

and 6 x CH],

Hz.

the

was evaporated

(19),

6C 18.04,

(3 H. s,

and

9 x CH,,

of

and triphenylphosphine solvent

26-

Triphylphosphine

A mixture

OH);

(2 8). 2 x CCH,),

6H 0.76

2 I,

6C 46.32

a,

(hexene-chloroform);

(Py);

(6H,

(lH, 50.56

C-N).

(1 H. d, J 8.5

s,

Procedure.-

(9, (dec.)

om-’

2 x CH,,

2.47

(lH,

1600

10.16

38.99,

wm

190°C

m.p. and

and

3 x CH,),

1.08

&J

38.68,

(dr

131.34

CH,).

3.0

(d,

pPm.

v(CC1,) 2 d,

(1 HI d,

3 x CH,).

3160

J 6.8 (25-CH,),

(2 H. m with

(OH),

Hz.

29-

3070, and

and d at d at

2.04,

CHeqCN).7.30-7.56,7.64-7.80(15 H. 2 m, 3 x Ph), and

10.43 (1 H. d, JHp 2.6 Hz. OH); 6p 30.83 ppm.

J

Functionalisation of unsctivataimethylgroups Preparation of 0-Acetyl

Pyridlne Complexes (6),

of the dimeric organopalladium compound (3). mmol), acetic

dichloranethane

(171, or (27) (0.33 nmol). trlethylamine

(20 al) was stirred

(MgSO,).

and stirred

for 15 h at room temperature.

acid,

(0.14 ml. 1.0

(6.0 188, 0.05 mmol) in

The resulting

solution was

sodium hydrogen carbonate , and water, the organic layer was

with pyridine

(0.052 ml, 0.66 mmol) for 10 min.

evaporated (15 mmtIg)and the residue recrystallized (20).

General Procedure.- A mixture

(30).

anhydride (0.094 ml, 1.0 anuol), and 4-dimethylaminopyridina

washed with diluted hydrochloric dried

(201, s

707

The solvent was

to afford the corresponding complexes (61,

and (30).

Complex (6). m.p. 190°C fdec.1 (hexane-chloroform);

VW&)

3070, 1600

(Pyf.

1775 (C-0).

and 1645

cm-’ (C-N); 6~ 1.30 (6 H, 8. 2 x CH,G), 1.88 (3 H, s, CHICI), 2.31 (5 H. s, CH,COand CH,Pd>, 7.29, 7.75.

and 8.75 (5 H, 3

CH,Pd). 49.84 (s, ccn,),

m,

Py);

6~

14.04

fq,

19.01 (q, CH,CO), 27.98 fq, $,C).

CH,CN).

41 .Ol (t,

124.76, 137.40, 152.75 (3 d, PY), 167.17 (9, C-N), an 192.04

Complex (Zo), m.p. 139-1400C (hexsne-chloroform); S.

CH&O).

(8 H. m with d at 2.03, J 7.4 Hz, 3 x CH, ring,

2.46 (1 H. PI. CHPd), 2.78 (1 Ii, m, CHeqCNlv

7.30.

and 8.72 (5 H. 3 m. Py); 6~ 18.95 (9. cH,CO), 21.61, 24.76, 26.18 13 t, 3 x CH, ring), cH,c),

C-0).

v(CHC1.1 3080, 1615. 1600 (Py), 1770 (C-O), and

1635 cm-’ (C-N); 6H 1.44 (3 H, 9. CH,C), 1.51-2.10 CHPd. and CH,,CN), 2.31 (3 ii,

ppm (9.

7.74,

27.38 (q,

40.48, 42.42 (2 t, CH,CNand CH,Pd), 49.89 fs, CCH,), 124.73. 137.37, 152.72 (3 d. Py),

167.34 (9, C-N), and 193.74 ppm (9. C-0). Complex (30). m.p. 125-1270C fhexane-chloroform); (C-O), and 1640 cm-’ (C-N); 6~ 1.17-1.77 CH, ring),

v(CC1.1 3100, 3080, 3050, 1615, 1600 fPy), 1780

(15 H, m with 3 8 at 1.25, 1.31. an 1.66, 3 x CH,C and 3 x

1.84 (1 H, d. 2 7.5 Hz, CHPd), 2.32 (3 H. 8, CH,CO), 2.46 (1 H, m, CHPd). 7.31, 7.75,

and 8.70 (5 H. 3 m, PY); 6~ 17.76, 37.85. 40.80 (3 t, 3 x CH, ring),

19.89 (q, ~H,Co, 26.64, 28.60,

31.64 (3 q. 3 x cH,C). 40.14, 51.72 (2 s. 2 x CCH,), 43.79 (t, CH*PH), 124.70, 137.22, 152.94 (3 d, Py), 167.79 (9, C-N), and 194.02 ppm (br 8, C-0). Preparation of the Deuterlated Oxlmes (71. (151 (21). a solution

(31). -and (41). General Procedure.- To (17). (27). or (38) (0.5 aynol) in

of the dimeric organopalladlum compound (31, (13).

tetrahydrofuran

(8 ml) an6 methanol (2 ml) was added a solution of sodium cyanoborodeuteride

(O.O66g, 1 amol) In tetrahydrofuran for 1 h allowing to warm it till

(4 ml) and methanol (1 ml) at O°C and the mixture was stirred

row temperature.

The black precipitate

was filtered

off,

the

solvents were evaporated (15 amHe>and the residue hyrolysed with water, extracted with dichloromethane, the organic layer dried (HgSO,), and evaporated (15 mmHg). The resulting recrystallized

to afford the deuterlated oximes (7).

(15).

(211, (31).

E~4-Deuteriopinacolone Oxime (7). m-p. 77-78OC (hexane-ch~orofo~); CID-’ (C-N); 6H 1.12 (2H. s, CH*D), 1.14 (6 H. 8, 2 x CHJ), 9,

restdue uas

and (41).

v~Nujo1) 3240 (OH) and 1650

1.88 (3Si. 9, CH,CN), and 9.17 (lH, br

OH); 6D (CHCl,) 1.165 (CH,D); 6~ 9.86 (q. CH,CN), 27.22 (tt,

&D 18.9 HZ, CH,D),, 27.51 (9.

C&C), 37.08 (9, ($H,).

and t64.63 ppm (a. C-N); -m/e 116 (M*). E-1-Acetoxy-2-deuteriomethyl-2-methylbutan-3-one Oxime. (151. m.p. 85-86oc (hexane); v(Nujol) (OH>, 1730 (C-O), and 1645 cm-’ (C-N); 6H 1.16 (5 H, s, CHICand CH,D),

3250

1.87 (3 H, s, CH&N), 2.07

(3 H. s, CH,CO), 4.06 (2 H, 8. CH,O). and -ca. 8.10 (1 H. br 8, OH); dD (CHCl,) 1.185 (CH,D); 6~ 9.95 (q, ;H,CN), 20.86 (q, CJH,CO),22.47 (tt, &D 19.7 Hz, CH,D), 27.77 (qr 2H.C). 40.56 (9, CCH,), 70.04 (t,

CH,O), 161.24 (9, C-N), and 170.98 ppm (s, C-0); .m/e ..- (DCI, NH,) (W++2). Oxime (211, m-p. 91-9206 (hexanef (Found: C, 67.5; H/D,

~-2-Deuteri~et~yl-2-methycy~lohexanone

10.7; N. 9.5. C,H,,DNO requires C, 67.56; H/D, 11.34; N, 9.85); (C-N); 6~ 1.05 (2 H, 9,

v(CHCl,> 3260 (OH) and 1660 cm-’

CH,D), 1.13 (3 H, s, CH,f. 1.44, 1.54 (6 H, 2 m. 3 x CH, ring),

2.56 (2H,

m, CH,CN), and 8.77 (lH, br s. OH); 6D (CHCl,) 1.185 (CH,D); 6D 20.72, 21.74, 26.07 (3 t. 3 ring),

26.30 (tt,

x CH,

&D 18.7 Hz. CH,D), 26.58 (q, CH,). 37.51 (se $CH,), 41.24 ft, gH,CN). and 165.63 ppm fs, C-N); -m/e 142 (?4+>.

708

J.E. BALDWINeIal.

g-2-Deuter1omethy1-2,6,6-tr1methy1cyc10hexanone Oxime (311,m.p. 152-154OC(hexane-chlorofoFm); v(Nujol)3300, 3220 (OH), and 1650 cm-' (C-N);6H 1.17, 1.18, 1.35 (11 H, 3 s, CH,D and 3 x CH,), 1.49-1.69(6H, 2 m, 3 x CH, ring), and 7.97 (1 H, br s, OH); 6D 9CHC1,) 1.223 9CH,D); 6C 17.46, 37.65. 40.61 (3 t, 3 x CH, ring), 26.90, 30.59 (2 9, 3 x CH,), 30.31 (tt,&D

20.1 Hz, CH,D),

37.04. 41.68 (29, 2 x CCH,), and 168.25ppm (s. C-N); m/e 170 @I*). E-23-Deuteriolupanone Oxlme (41),q.p.>2lOoC(ethylacetate-chloroform); v(Nu.jol) 3240 (OH) and 1650 cm-' (C-N);&H 0.76 (3 H, s, 28-CH,),0.76. 0.84 (6H, 2 d, J 6.7, 29- and 30-CH,),0.92, 0.95 (6 H, 2 s, 26- and 27-CH,),0.97-2.00[32 H, m with 2 s at 1.05 and 1.07 (24- and 25-CH,),and d at 1.13,J 5.6 Hz (23-CH,D),2 x CH,, 9 x CH, and 6 x CHI, 2.26, 2.98 (2H. 2 m, CH&N). and 7.27 (1 H, br s, OH); 6D (CH,Cl,)1.14 (CH,D);6C 27.07 (tt,JCD = 19 Hz, CH,D), and 167.49ppm (s. C-N);'* m/e (DCI,NH,) 444 (l4++2). -Chlorinationof Compound (3). E-4-Chloropinacolone Oxlme (8).-Througha solutionof compound (3) (0.147g, 0.287 mmol) in carbon tetrachloride(20 ml) was bubbledchlorinefor 30 min. The solventwas evaporatedand the residuedissolvedin tetrahydrofuran (4 ml) and methanol (1 ml). To the resultingsolutionws added sodium cyanoborohydride (0.038g, 0.574 awol) in tetrahydrofuran (4 ml) and methanol (1 ml) at OoC and the mixturewas stirredPor 30 min. The black precipitate was filteredoff, the solventsvere evaporated(15 mmHg), and the residuewas extractedwith ether. The solventwas removed (15 nxnHg)to aPford the title compound(0.055g. 61(S), m.p. 60-620C (hexane);v(CHC1,)3300 (OH) and 1660 cm-' (C-N);6~ 1.23 (6H, S, 3.57 (2

2 x CHIC), 1.90 (3 H,

S,

CH,CN),

H, s, CH,Cl),and 8.79 (1 H, br s, OH); 6C 10.01 (q, sH,CN), 23.64 (q, 2 x CHIC), 42.25 (s,

CCH,), 52.73 (t, CH,Cl),and 160.99ppm (s, C-N); -m/e 150 (M*+l,for "Cl). OxidationoP Organopalladium Compounds(31, (13). (171, (201, (271, (301,-and (38) with Lead Tetraaoetate(Pd:Pbmolar ratio 1:l). Isolationof AcetoxyDerivatives(91, (111, (16), (221, compound (231, (32),-and (42). GeneralProcedure.-To a solutionof the dimericorganopalladium (31, (131,or (17) (0.4 am101)in tetrahydrofuran (15 ml) was added pyrldine(0.06 ml, 0.8 mm011 and stirredfor 10 min. Then, a solutionof lead tetraacetate(0.35g, 0.8 mol) in acetic acid (5 ml) vas added to the resultingpyridinecomplexat OoC, and the mixturewas stirredfor 2 h allowingto rise the temperatureto 20°C. A solutlonof sodium borohydride(0.03g, 0.8 mmol) in 1 N aqueous sodium hydroxide(5 ml) was then added, and stirredfor 30

min.

The black suspensionwas filtered,

the filtratewas extractedulth ether,washed with water and sodium hydrogencarbonate,dried (Mgso,),and evaporated(15 mmHg) to afford the products(91, (161, and (221,which were distilled and/or recrystallized.In the case of the preparationof products (23) and (32) the oxidationwas carriedout as it was above describedstartingdirectlyfrom the pyridineComplexes(20) and (30). In the case of the oxidationof compounds(3) and (38) to give the products (11)

and

(421,

respectively,the acetylatlonof the corresponding dimericorganopalladium compoundwas carriedOut prior to the In situ oxidation,which was performedas it was above described. E-4-Acetoxypinacolone Oxime (9). m.p. 85-86OC (hexane)(Found:C, 55.9; H, 8.8; N, 7.9 C,HISNOI requiresC. 55.47; H, 8.73: N, 8.09; v(Nujol)3250 (OH), 1730 (C-0).and 1645 cm-' (C-N);6H 1.15 (6 H,

2

S,

x

CH,C), 1.87 (3 H, s,

CH,CN),

2.06

( 3 H,

9.

CH,CO),

4.07

(2

H,

9.

CH1O),

and 8.46 (1

H, s, OH); 6C 10.03 (q, CH,CN), 20.83 (q, cH,CO), 22.77 (q, CHIC). 40.60 (s, CCH,), 70.01 (t, CH,O), 161.10(s,C-N), and 170.98ppm (9, C-0); -m/e (CI, NH,) 175 (M*+2). E-4-Acetoxy-0-acetylpinacolone Oxime (11).011; v(neat.1 1740 (C-0) and 1630 cm-' (C-N);6H 1.22 (6 H,

S,

2

x

CH,CN). 2.05

(3

H, s, CH,CO,C).2.19 (3 H, s, CH,CO,N),and 4.10 (2H. s. CH,O); 6C 12.05

(q. CH,CN), 19.87,20.79 (2 q. 2 x cH,CO), 22.68 (q, cH,C). 41.52 (s, CCH,). 69.68 (t, CH,O), 168.35, 169.29,and 170.76ppm (3 s. C-N and 2 x C-0); -m/e (DCI,NH,) 216 (M*+l). E-1-Acetoxy-Z-acetoxymethyl-2-methylbutan-3-one Oxime (161, m.P. 45-47OC (hexane-chloroform); -V(CCI,) 3460. 3315 (OH), 1735 (C-0).and 1640 cm-' (C-N);6~ (3 H, s, CHIC), 1.88 (3 H, s, CH.CN), 2.06 (6~, S,

2

x

CH,CO), 4.16, 4.21 (4H. 2 d, J 11.5 Hz, 2 x CH,O), and 8.13 (1 H, br 9, OH); 6c

10.03 (q, CH,CN), 18.22 (q. cH,C), 20.79 (q. cH,CO), 43.91 (s. CCH,), 65.70 (t. CHSO), 158.35 (9. C-N). and 170.76ppm (s, C-0); --m/e

(CI, NH,) 233

#+*2).

of unactivatcd methyl groups

Functionalisation

E-P-Acetoxymethyl-2-•ethylcyclohexanona (OH),

1740 (c-o),

and 1650 cm-’

2.06

(3 H,

S,

(lH,

br

OH); 6c 20.84,

36.13 199

S,

(t.

CH,CO), 2.51-2.66

CH&N),

(s,

6~ 1.17

25.51

ccH,),

69.10

4.20

3 x CH, ring).

(t,

CHIO). 162.16

tig,

Kugelrohr);

1.46-1.73

v(neat)

3400

(6H, m. 3 x CH, ring),

(2 H, 2d, J 11.0 Hz, CH,O), and 8.96 20.84 (9,

(q. ~H,CO),

C-N),

21.94

and 171.07

(9. c&C),

PPm (s,

C-0);

m/e

@I’).

(C-N); 2.60

6~ 1.26

(3 H, s,

(2H. m. CH,CN),

20.49,

23.26,

CH,O).

CH,C),

and 4.34

4.2,

25.65

(3 t.

169.53,

1.55-1.78

(2 H. 2 d, 211.2

3 x CH, ring).

169.78

and 170.88

(23).

Oxlme

1630 cm-’ H, 2 s,

(C-N);

6~ 1.29,

2 x CH,CO),

CH, ring). CCH,),

20.07, 71.34

1.33

22.01

20.87

(t.

CHIC),

oxima 1.47-1.80

3 xCH,),

(t. (321,

27.53,

and 172.85

011;

and 1625 cm-’

(6 H, 2 8, 2 x CHJO).

20.38

sH,CN),

m/B (CI.

(2 9, 2 x cH,CO),

41.91

(s,

CCH,),

27.69

v(neat)

6C 17.04,

(3 q,

ppm (3 s,

68.82

NH,) 242 (M’*l). 1745 (C-0)

(6 H. m. 3 x CH, ring),

(2 H, 2 d, J 10.7 HZ, CH,O); 170.78

1750 (C-0).

2.18

6C 19.90.

36.29

C-N and 2 x C-0);

(2 q, 2 x CHICO). 26.51,

CH*O), 169.16.

v(CC1.j 2.07,

Hz, CH,D);

(q,

ppm (3 s,

(9 H, 2 9.

and 4.31

4.07,

011;

(6 H, m. 3 x CH, ring).

E-2-Acetoxymethy1-0-acety1-2,6,6-tr1emthy1cyc1ohexanone

x

125OC (0.1

t.

(3

E-L-Acetoxymethyl-0-acetyl-2-methylcyclohexanone

(t,

b.p.

(3 H, 9, CH,C).

(2H. m. CH,CN), 4.08,

21.21,

40.89

Oxime (22),

(C-N);

709

32.80,

3 x cH,C),

2.06,

40.51 37.86,

C-N and 2 x C-O);

and 2.19

(3 t. 42.22

m/e (Cl,

(6

3 x (2 s,

2

NH,) 270

(M++l). 23-Acetoxy-0-acetyllupanone 1626 cm-’ 0.93

(C-N);

(6 H. 2 s,

(3 H, s,

28-CH,).

and 27-CH,).

26-

011;

Oxime (42).

6~ 0.76

0.97-1.91

x CH,. 9 x CH,, and 6 x CH]. 2.06, (2H. 2 d, J 11.0 Hz. CH,O);

+16.55o(c 0.84

1.4.

CHCl,);

(6 H, 2 s,

(t,

2 x CH,CO), 2.64

169.65,

CH,O),

v(neat)

1740 (C-0)

and

(6 H, 2 d. J 6.7 HZ, 29- and 30-CH,).

[30 H, m with 2 s at 1.07

2.17

6C 68.29

[a]‘;

0.76,

(25+X,),

and 1.17

0.90,

(24-C%),

(2 H. m. CH,CN). 4.09,

and 170.84

ppm (2 s.

2

and 4.19

C-N and 2 x C-O);

m/e

(DCI, NH,) 543 (M++2). Oxidation 1:2).

of Organopalladlum

Isolation

palladium

compound (3)

ml) was stirred acetic

acid

the solvent

(17)

Por 10 min.

carbonate,

ether,

(12),

2.03

20.68

(q, CHJO,).

21.68

OC-0).

and 210.89

ppm (s,

1OOcC (0.1 (3 H, s,

(q, cH,C). C-0);

(C-0);

6~ 1.14

2.36-2.53 170.92

(3 H, s.

(CI,

20.95,

(s,

27.08,

OC-01,

Hydrolysis

(0.155

was relluxed

Por 15 h.

treated

with water

and the solvent the title UO-’

(H++2).

(q.

g,

0.89

evaporated

6H (CDCl,-D,O)

cH,C).

42.13

(s.

b.p.

g,

3511,

1.06

(6 H.

v(neat)

130°C (0.1

solution

(12)

oP sodium

or (241,

1750 and 1710 cm-’

CHJO) and 4.10 CCH,),

69.82

(2 H. s, (t,

nraHg, Kugelrohr);

J

which

(C-0);

6~

CH,O);

CH,O),

48.59

6C

170.66

(s,

4-Hydroxypinacolone hydroxide

(0.050

The residue 80-82oC x

CCH,),

20.81

68.67

2H.C

(2 q.

ct.. CH,O),

(Lit..”

m.p.

and 3.54

and 163.54

(15 amIHg) an the residue The organic

H.

layer

was dried

(hexane-chloroiorm)

82%); (2

A mixture

1.0 mmol) in ethanol

was recrystallized

CH,C),

ct.. CH,O),

Oxime (10).

g.

was evaporated

with dichloromethane.

2

6C 20.65.

1745 and 1715 CH,CO,).

(DCI, NH,) 186 (t4**2).

the solvent

S.

(s.

v(neat) (3 H, s,

2.04

Hz. CH,O);

11.0

4 x CH, ring),

m/s

Oxlme (9).

m.p.

CCH,) 70.15

at room temperature,

the crude product

47.56(s,

(2 H, 2 d.

(4 t,

(15 mmHg).

in

(5 ml) was

nashed with water and dried

(6 H, m, 3 x CH, ring),

prpol) and potassium

APter cooling

layer

(3 H, s,

(q, cH,CO),

C-O);

(2 ml) and extracted

compound (0.041

(C-N);

22.70

38.77

oP 4-Acetoxyplnacolone

compound (9)

2.16

1.63-1.96

ppm (s.

Por 2 h, cooled

acid

NH,) 160 (M+*2).

and 4.17

36.16,

and 212.88

was suspended

0.8 um101) in acetic

was washed with an aqueous

nWlg, Kugelrohr);

(210,

CHIC).

(2 H, m, CH,CO), 4.12,

and cH,CO),

was rePluxed

CHJO,).

2-Acetoxymethyl-2-methylcyclohexanone cm-’

8,

(10

pressure.

25.33

m/s

(15 IrmHg), the residue

(15 mmHg) aiiorded

under reduced b.p.

2 x CH,C),

ml, 0.8 mm011 in tetrahydroiuran

(0.35

and the ethereal

oP the solvent

by distillation

(6H. s,

tetraacetate

The mixture

with

(0.063

was evaporated

oP lead

(15 nnnHg) and the residue

extracted

4-Acetoxypinacolone

mmol) and pyridine

suspension.

The evaporation

(MgSO,).

(0.4

The solvent

was evaporated

was puriiied 1.16

or

(5 ml) and a solution

added to the resulting hydrogen

Compounds (3) -and (17) with Lead Tetraacetate (Pd:Pb molar ratio General Procedure.A mixture oP dimeric organo-

oP Compounds (12) and (24).

v(Nujol) 8,

ppm (9.

CH,O);

C-N);

3300

(CI,

was (HgSO,) to aPPord

(OH) and 1640

6C 10.02

m/s

oP

(15 ml)

(q, CH,CN), NH,) 133

J. E. BALDWIN et al.

710 X-Ray Structure monoclinic, - 1.656

determination

a - 10.648(4)

g cm-‘.

u(Mo - K,)

An orange

crystal

chromator. 550.

- 14.3 cm-‘.Space

varied

A total

of

with

effects

I > 3(0)1

isotropic

and followed

by anisotroplc

difference

Fourier

reflection

which showed gross

n - 361.16,

Aa. 2 - 4, Dc

‘ride’

equipped for

Data collection

with a graphite

reflections

in the range 0 < 28 <

upon the intensity

factors

of

by full

matrix

factors.

All

Lorentx

and gave 2874

The structure least

the

for

1.78 - 2.01)”

calculations.

mono-

squares,

was solved

first

hydrogen atoms were located

uas omited

from the refinement.

term Chebyshev series

in

One

The weight

whose coefriolents

by

with

on the atoms to which they were bonded.

effects

from a three

from

x 0.63 x 0.73 mp.

depending

transmission

temperature

extinction

was calculated

U - 1448.1

were measured which were corrected

methods , and refined

maps and were made to

Data C,,H,,N,OPdCl

by recrystallisation

of 0.48

the m-20 scan technique

(relative

density

4342.1

was obtained

which were used in subsequent

and electron

Crystal

diffractometer.

3325 unique reflections

Patterson

each reflection

(18)

dimensions

between 1.1 and 6.7 deg/mln

and absorption

reflections

using

(18).

A. 8 - 106.83(2)0,

group P2,/c.

complex

with a CAD-4 computer controlled

Data were collected

polarisation

complex

c - 9.620(2)

which had approximate

The scan rate

reflection.

the pyrldine

of the pyridine

dichloromethane/hexane was performed

for

b - 14.769(3),

for

were 3122.6,

and 1313.9."

The refinement performed

converged

with a final

the CRYSTALS” package

with

R value

of

on the Chemical

0.042

(Rw - 0.043).

Crystallography

All

calculations

Laboratory

were

VAX 11/750

computer. Tables

of atomic

coordinates.

Cambridge Crystallographic

bond lengths

Data Centre,

and bond angles

University

Chemical

have been deposited

Laboratory,

Lensfield

at the Road, Cambridge

CB2 1Ew. REFERENCES AND NOTES

1.

Permanent address: Oviedo.

2.

For a recent

3.

0. E. Hartwell,

V. I.

Departamento

review

Sokolov,

see:

J.Organomet.Chem.. Y. Fuchita,

5

A. C. Constable,

6.

Facultad

de Qulmica,

Universldad

de

and T. Uchiyama, Dalton Trans.,

on the palladation

appeared:

K.Carr

of the present

8.

R. A. Holton

9.

When the reaction

1984.

L. I.

J.Chem.Soc.,

of

1980,

40. 2415. Chem.Commun., 1970,

Solovieva,

912;

and 0. A. Reutov,

Dalton

Trans.,

1983,

897.

and 8. L. Shau, J.Chem.Soc.,

Chem.Cmun.,

1992. and lanost-8-en-3-one-

2,2,6-cyclohexanone-

and J. K. Sutherland,

work has been submitted

and M. Yus, J.Chem.Soc.,

reaction

L. L. Troitskaya,

W. G. McDonald, L. C. Sawklns,

A communication

A part

Tetrahedron,

and M. J. Smas, J.Chem.Soc.,

1972. 36. 389.

K. Hlrakl,

1061; J.Chem.Soc.,

recently 7.

L. H. Hegedus,

R. V. Laurence, J. A. Soroklna,

4.

1978,

de Pulmica Organica.

Spain.

J.Chem.Soc..

oxlme

Chem.Commun., 1984,

in a preliminary

form:

has

1227.

J. E. Baldwin,

C. Najera,

removes Pd(IIl

from the

Chem.Commun.

and R. A. Kjonaas, product

J.Am.Chem.Soc.,

is an oxlme derivative

1977, 99, the final

4177. reduction

product.

10.

J.

11.

A. K. nahapatra.

E. B&ckvall

and E. E. BJdrkman, J.Org.Chem., D. Bandyopadhyay.

1980,

P. Bandyopadhyay,

45,

2893.

and A. Chakrovorty,

J.Chem.Soc.,

Chem.Commun., 1984. 999. 12.

Y. Yukawa, H. Sakal,

and S. Suzuki,

13.

G. Just

Can.J.Chem..

14.

and K. Dahl,

P. A. S. Smith,

‘Open-Chain

Bull.Chem.Soc.Jpn.,

1966, 39, 2266.

1970. 48. 966.

Nitrogen

Compounds’,

Vol.11,

W. A. Benjamin,

pp.30-36 15.

F. E. King,

T. J. King,

16.

F. Johnson,

Chem.Rev.,

and J. G. Topllss, 1968.

68. 375.

J.Chem.Soc.,

1957, 919.

Inc.,

New York,

1966,

Functionaliaation of unactivated methyl groups

17.

J. M. Conla,

18.

Bellstein,

Bull.Chsm.Soo.Fr.,

711

1950, 537.

1, 14.

19.

J. Colonge,

20.

Bellstein,

Bull.Chem.Soc.Fr.,

21 .

Bailstein,

7, 98.

22.

Bellstein,

7,

23.

A. C. Constable,

7,

1938,

98.

156. 112. W. S. MoDonald. 8. Odell.

and B. L. Shaw. J.Chem.Soc.

Dalton

Trans.,

1983.

2509. 24.

We thank Dr. T. G. Halsall

25.

I.

26.

A. J. Mncuso,

27.

We thank Dr. A. Derome for

28.

J. Tsuji,

29.

The signal

30.

Beileteln,

H. Heilbron,

a gift

of lupenyl

acetate.

J.Chem.Soc.,

S. L. Huang, and D. Swern, J.Org.Chem.,

‘Organic

III,

31.

A. C. T. North,

32.

J. R. Carruthera

33.

D. J. Watkin

1938,

1978,

329.

43, 2480.

the NOg studies.

Synthesis

at 27.41

with Palladium

ppm corresponding

oxime is not present

Laboratory,

for

T. Kennedy , and F. S. Spring,

in this

COrnpounds’,

Verlag,

Springer

to the 23-CH, in the

“C

n.m.r.

Berlin.

spectrum

1980, p 2. of lupanone

spectrum.

1, 3239. D. C. Phillips

and F. S. Hathewe, Acta Crystallogr.,

and D. J. Yatkln,

and J. R. Carruthers, University

of Oxford,

Acta Cryatallogr.,

WtYSTALS, Users Guide”, Oxford,

1982.

1968, A24. 351.

1979, A34, 698. Chemical

Crystallography