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Organo tin nucleophiles IV. Palladium catalyzed conjugate reduction with tin hydride
Tetrahedron Printed in
Letters,Vol.23,No.4,pp Great Britain
477-480,1982
0040-4039/82/040477-04$03.00/O 01982
ORGAN0
Pergamon
Press
Ltd.
TIN NUCLEOPHILES IV?
PALLADIUM CATALYZED CONJUGATEREDUCTION WITH TIN HYDRIDE
Ehud Keinan* Department
of
Organic
Chemistry,
and Pierre
The Weizmann
A. Gleize
Institute
of
Science,
Rehovot,
Israel
Abstract: Highly chemoselective conjugate reduction of a,@-unsaturated carbonyl now possible by using tributyl tin hydride with Pd(P@5)4; an optimization study importance of added radical scavenger and proton source in these reductions.
Chemoselective functions, tools
has been
and regiooffer
hydrogenation
has been
strikingly
a number of
of
The ability fashion
Herein
is
based
The reaction
of
as n-ally1 tin
suggested
over
to
the
hydrides the more
perform
a new highly
on trialkyl
tin
nucleophiles
hydride
serves
last
extent
chemoselective hydride
transfer
relevant
of
chemoselectivity
of
metal
catalytic
synthetic
hydrides,
hydrogenation2
metallic hydrides used are 7 ruthenium, 8 iridium,’ cobalt,
on highly
bound
of
palladium
as an hydride
has been
protonation,
In terms
tile
carbonyl
of
transition
methods
significant
reduction
as a,B-unsaturated
The arsenal
two decades.
traditional
to
functionalized
hydride
to
tin
reported, 12 to donor
hydride
should
catalyzed
donor
trialkyl
previously
as an efficient
an analogous
by concomitant
such
is
forth
and
molecules
in
challenge.
covalently species
bonds
and in particular
conjugate
a continuing
palladium
that
followed
within
metal
poses
reported
methodology,
tributyl
double
transformation.
reduction methods.> The most 4 5 6 rhodium, and to a lesser copper,
a controlled
such
enriched
advantages
activated
synthetic
metal
iron, 10
palladium.
of
desired
and stereocontrol,
and dissolving those
a long
compounds puts
activated
result
in net
conjugate
and water with 1,ll
reduction
as a proton
soft
electrophilic
Our recent
*-ally1
centers
finding
palladium
olefin-palladium conjugate
donor.
that
complexes,
complexes
reduction
of
Michael
acceptors. Indeed,
addition
of
tributyl
carbonyl
compound
containinga3
work-up,
resulted
in
in Table
I.
The striking bond,
Since sirable role of
side
the
the
reaction
reactions
and relative factorial
excellent
yield
sensitivity
as demonstrated
of
in Table
the
I,
involves
hydride
of
of
of
the
experiments
carbonyl
to
potential
organometallic
products,
THF solution
room temperature,
system
a great
a number of
a stirred at
a,@-reduced
reducing
holds
five
to
% Pd(Pp)3)4
and decomposition
importance plane
tin mole
the
species.
electronic
in terms
by H20/CH2C12
Results
are
shown
at the
double
chemoselectivity.
which study
different factors were evaluated, 13 as depicted in Table II.
477
an a,S-unsaturated
density of
species
an optimization
of followed
may lead
to
was carried
based
on 8
undeout.
x
The
8 matrix
478
Table
I.
Starting material
Conjugate
reduction
Bu3SnH (addition 1 eq./h)
with
Bu3SnH/Pd(P$3)4
rate
Product
(Yield) CHO
1.5
eq.
1.5
eq.
(Bu3SnD)
1.5
eq.
(work
1.7
eq.
(’ 99%)
(> 99%)
up with
D20)
(>99%)
CHO (98%)
3 eq.
(70%) recovered starting
4 eq. 1.7
material
(0%)
n
cl+
eq.
(>99%)
0
The semi-quantitative meters slow
(eq.
1)
hydride
presumably of
or
wise
addition
between
after
the
1)
Yield
(eq.
the
the
Under the
simplex
dozen
(%) = 20.7 optimized by the
Interestingly, as judged
addition
rate. (Table
of
conditions,
quantitative
Tributyl hydride ZnC12,
donor 17 sio
both
tin
hydride,
properties 18 or in
2’ played here by addition 20 tion conditions, the when the example
reaction of
tin
- 11x3
2
only
of
a typical
in
of
to
above
para-
the
effect
reaction
in favor
and radical
consideration,
an essentially
and
scavena step-
quantitative
- 8.9X4
- 3.5x5
+ 1.92x1x2
trisubstituted
- 2.42XlX3
olefins
were
were
reduced
also
reduced
citral:
w”
,
the
commercial
free-radical
two general
combination
1:l
mixture
at
the
with
cases:
highly
reducing either
in
electrophilic
agent,
highly partners.
15,16
polar 19
same
has
exhibited
medium containing The beneficial
role
a radical
need
was followed hydride
led
suppresses solvent
temperature
on the
III)
chosen
temperature
analysis. being
of
hand,
a small
between
Based
conjugated
reduction
z and E isomers
G.C.
is
first
higher
experiments.
98%
by the
other
There exists
and these
scavenger,
on the
catalyst.
method l4
-0
rate
yield
radical
phosphine,
+ 10.4X 1 + 5.3x
set
product’s
added
correlation
and hydride
modified
the of
palladium
no significant
resulting
as demonstrated
roles
Added triphenyl
temperature of
between
beneficial
rate.
Apparently,
sequence
yield
the
by over-stabilizing
benzene.
ger
correlation
revealed
acting
for
scavenger, the inertness of the benzyl chloride to the reac18 one equivalent of Bu3Snll and the absence of CIDNP effects 21 by NMR, suggest the present hydrogenation to be another rare only
as an hydride
donor.
A plausible
mechanism
involves
palladium
479
Table
II.
Factorial
plane
of
experiments
x2
x3
x4
x5
-
-
+
-
for
reduction
of
8 iononea
W-W Exp. No.
x1
l+-
Yield
xlx2
x1x3
+
+
5.4
(%)
2++--++
-
-
29.6
3+-+--+
-
+
25.7
4
++
+
-
-
-
+
65.8
5+--+-+
+
-
5.6
6++-+--
-
+
21.0
-
4.4
+
+
7.7
7+-+++-a++++++ a)
In each
experiment
and 0.03
a 5 ml solution
mmole Pd(P$3)4
(temperature)
containing
was subjected
to
:
(2,6-di-t-butyl-4-methylphenol):
1 mmole 8 ionone
the
following
rate
(solvent)
Table exp. no.
temp.
of
Bu3SnH):
:
Simplex
III.
optimization
of
23’C
-
0.06
mmole
0.24
mmole
1 mmole/h
6 mmole/h
benzene
THF
8 ionone
reductiona
radical scavenger
solvent/proton source
yield
70.3%
9
4o”
0.48
eq.
benzene
10
60’
0.72
eq.
benzene
11
3o”
0.42
eq.
THF/H20
12
3o”
conditions:
O0
(triphenylphosphine): (addition
-c
29.7% (2.8
THF/H20 2.7
83.8%
eq.) (eq.)/
>98%
NH4C1 (2 eq.) a)
In each solution
catalyzed conditions
hydrostannation to
the
The expected stenone
or even
chemoselectively
parent
experiment
Bu3SnH was added
of
1 mmole f3 ionone
to
form
carbonyl
importance
of
an intermediate 22 compound.
steric
A1’4-cholestadienone reduced
in
and 0.03
excellent
factors to
this
yield:
enol
at
a rate eq.
1 eq./hr
to
a 5 ml
Pd(P$3)4.
stannane
was demonstrated reducing
of
system,
which
by the whereas
decomposes
resistance withanolide
under
protic
of A4-chole23 was D
480
OH OH in situ utilization of the intermediate Further scope and limitation studies, as well as -1 en01 stannane are in progress. AcknowledRement.
We
wish to thank the Sir Charles Clore - Weizmann Fund Post Doctoral Fellow-
ship and the U.S.-Israel Binational Science Foundation for their generous support. References
1) 2) 3)
4) 5)
6)
7) 8) 9) 10) 11)
12) 13) 14) 15) 16)
17) 18) 19) 20) 21) 22) 23)
For early work in this area see: B.M. Trost and E. Keinan, Tetrahedron Lett. 2591, 2595 (1980). a. R.L. Augustine, "Catalytic Hydrogenation", Marcel Dekker, N.Y.C. (1965); b. M.Freifelder, "Catalytic Hydrogenation in Organic Synthesis", Wiley, N.Y. (1978). a. M. Smith in "Reduction", p. 95-170, R.L. Augustine Ed. Marcel Dekker, N.Y.C. (1968); b. A.J. Birch and H. Smith, Q. Rev. Chem. Sot., 12, 17 (1958); c. H.O. House "Modern Synthetic Reactions". D. 173-181. W.A. Beniamin. Menlo Park Ca. (1972). J.P. Collmg, R.G. Finke, P.L. Matlock, R. Wahren, R.G: Kombto and J.I. Brauman, 3. Amer. Chem. Sot., 100, 1119 (1978) and ref. cited therein. a. T. Tsuda, T. Fuhii, K. Kawasaki and T. Saegusa, J. Chem. Sot. Chem. Comm., 1013 (1980); b. E.C. Ashby, J.J. Lin and A.B. Goel, J. Org. Chem., 2, 183 (1978); c. M.F. Semmelhack and R.D. Stauffer, J. Org. Chem., 40, 3619 (1975); d. S. Masamune, G.S. Bates and P.E. Georghiou, J. Amer. Chem. Sot., s, 3686 -974); e. R.K. Baeckman Jr. and R. Michalak, J. Amer. Chem. sot.. 96. 1623 119741. a.1: vima and-T. Kbgure, Tetrahedron Lett., 5085 (1972); b. T. Hayashi, K. Yamamoto and 111. Kurnada,Tetrahedron Lett., 3 (1975); c. A.J. Birch and K.A.M. Walker, J. Chem. Sot.(C) 1894 (1966); d. R.E. Harman, J.L. Parsons, D.W. Cooke, S.K. Gupta and J. Schoolenberg, J. Org. Chem., 34, 3684 (1969); e. J.F. Biellman and M.J. Jung, J. Amer. Chem. Sot., 2, 1673 (1968); f. F.H. Jardine and G. Wilkinson, J. Chem. Sot. (C), 270 (1967); g. J.P.Candlin and A.R. Oldham, Discuss, Faraday Sot., 46, 60, 92 (1968); h. T. Kitamura et al. Chem. Lett., 379 (1973), 203 (1975). a. D.L. Reger, M.M. Habib and D.J. Fauth, J. Org. Chem., 34, 3860 (1980); b. J.Kwiatek, Catal. Rev., 1, 37 (1967); c. R.W. Goetz and M. Orchin, J.xmer. Chem. Sot., E, 2782 (1963). Y. Sasson and J. Blum, J. Org. Chem., 40, 1887 (1975). J. Blum et al., Tetrahedron Lett., 192571981)*. N.A. Cortese and R.F. Heck ,,J. Org. CF., 43, 3985 (1978). a. J. Godschalx and J.K. Stille, Tetr edron Lett., 2599 (1980). Fox-relatedwork see also: b. D.Milstein and J.K. Stille, J. Amer. Chem. Sot., 101, 4981, 4992 (1979), J. Org. Chem., 44, 1613 (1979). E. Keinan and N. Greenspoon, accompanying manuscript in this issue. O.L. Davies Ed., “The design and analysis of industrial experiments", Oliver andEoyd, London (1954). G.E.P. Box and D.W. Behnken, Ann. Math. Statist., 2, 838 (1960). H.G. Kuivila. Svn.. 499 (19701. Non selective conjugate reduction with Bu SnH via a free radical mechanism is reported to require photochemical or thermal (15O'C) snitixon: a. M. Pereyre, G. Colin and J. Valade, Tetrahedron Lett., 4805 (1967); b. M. Pereyre and J. Valade, Tetrahedron Lett., 489 (1969). W.P. Neumann and E. Heymann, Ann., 683, 11, 24 (1965). N.Y.M. Fung, P. DeMayo, J.H. bauble and A.C. Weedon, J. Org. Chem., 9, 3977 (1978) and references cited therein. A.J. Leusink et al., J. Organomet. Chem., 13, 155, 163 (1968). Reduction of an equimolar mixture of benzalacetone and benzyl chloride resulted in quantitative reduction of the first compound and the recovery of the unreacted benzyl chloride. The reaction was followed by 270 MHz NMR, with spectra being recorded every ten seconds. An analogous stepwise conjugate reduction based on rhodium catalyzed hydrosilylation, followed by acid hydrolysis has been reported (see ref. 6a,b), however, lower selectivity was noted (e.g. compare-reductionof 8 ionone). F.W. Eastwood,I. Kirson, D. Lavie and A. Abraham, Phytochem., 19, 1503 (1980).Applfcation of this method to selective transformations in the Withanolide series will be published elsewhere. (Received in UK 20 November 1981)
Letters,Vol.23,No.4,pp Great Britain
477-480,1982
0040-4039/82/040477-04$03.00/O 01982
ORGAN0
Pergamon
Press
Ltd.
TIN NUCLEOPHILES IV?
PALLADIUM CATALYZED CONJUGATEREDUCTION WITH TIN HYDRIDE
Ehud Keinan* Department
of
Organic
Chemistry,
and Pierre
The Weizmann
A. Gleize
Institute
of
Science,
Rehovot,
Israel
Abstract: Highly chemoselective conjugate reduction of a,@-unsaturated carbonyl now possible by using tributyl tin hydride with Pd(P@5)4; an optimization study importance of added radical scavenger and proton source in these reductions.
Chemoselective functions, tools
has been
and regiooffer
hydrogenation
has been
strikingly
a number of
of
The ability fashion
Herein
is
based
The reaction
of
as n-ally1 tin
suggested
over
to
the
hydrides the more
perform
a new highly
on trialkyl
tin
nucleophiles
hydride
serves
last
extent
chemoselective hydride
transfer
relevant
of
chemoselectivity
of
metal
catalytic
synthetic
hydrides,
hydrogenation2
metallic hydrides used are 7 ruthenium, 8 iridium,’ cobalt,
on highly
bound
of
palladium
as an hydride
has been
protonation,
In terms
tile
carbonyl
of
transition
methods
significant
reduction
as a,B-unsaturated
The arsenal
two decades.
traditional
to
functionalized
hydride
to
tin
reported, 12 to donor
hydride
should
catalyzed
donor
trialkyl
previously
as an efficient
an analogous
by concomitant
such
is
forth
and
molecules
in
challenge.
covalently species
bonds
and in particular
conjugate
a continuing
palladium
that
followed
within
metal
poses
reported
methodology,
tributyl
double
transformation.
reduction methods.> The most 4 5 6 rhodium, and to a lesser copper,
a controlled
such
enriched
advantages
activated
synthetic
metal
iron, 10
palladium.
of
desired
and stereocontrol,
and dissolving those
a long
compounds puts
activated
result
in net
conjugate
and water with 1,ll
reduction
as a proton
soft
electrophilic
Our recent
*-ally1
centers
finding
palladium
olefin-palladium conjugate
donor.
that
complexes,
complexes
reduction
of
Michael
acceptors. Indeed,
addition
of
tributyl
carbonyl
compound
containinga3
work-up,
resulted
in
in Table
I.
The striking bond,
Since sirable role of
side
the
the
reaction
reactions
and relative factorial
excellent
yield
sensitivity
as demonstrated
of
in Table
the
I,
involves
hydride
of
of
of
the
experiments
carbonyl
to
potential
organometallic
products,
THF solution
room temperature,
system
a great
a number of
a stirred at
a,@-reduced
reducing
holds
five
to
% Pd(Pp)3)4
and decomposition
importance plane
tin mole
the
species.
electronic
in terms
by H20/CH2C12
Results
are
shown
at the
double
chemoselectivity.
which study
different factors were evaluated, 13 as depicted in Table II.
477
an a,S-unsaturated
density of
species
an optimization
of followed
may lead
to
was carried
based
on 8
undeout.
x
The
8 matrix
478
Table
I.
Starting material
Conjugate
reduction
Bu3SnH (addition 1 eq./h)
with
Bu3SnH/Pd(P$3)4
rate
Product
(Yield) CHO
1.5
eq.
1.5
eq.
(Bu3SnD)
1.5
eq.
(work
1.7
eq.
(’ 99%)
(> 99%)
up with
D20)
(>99%)
CHO (98%)
3 eq.
(70%) recovered starting
4 eq. 1.7
material
(0%)
n
cl+
eq.
(>99%)
0
The semi-quantitative meters slow
(eq.
1)
hydride
presumably of
or
wise
addition
between
after
the
1)
Yield
(eq.
the
the
Under the
simplex
dozen
(%) = 20.7 optimized by the
Interestingly, as judged
addition
rate. (Table
of
conditions,
quantitative
Tributyl hydride ZnC12,
donor 17 sio
both
tin
hydride,
properties 18 or in
2’ played here by addition 20 tion conditions, the when the example
reaction of
tin
- 11x3
2
only
of
a typical
in
of
to
above
para-
the
effect
reaction
in favor
and radical
consideration,
an essentially
and
scavena step-
quantitative
- 8.9X4
- 3.5x5
+ 1.92x1x2
trisubstituted
- 2.42XlX3
olefins
were
were
reduced
also
reduced
citral:
w”
,
the
commercial
free-radical
two general
combination
1:l
mixture
at
the
with
cases:
highly
reducing either
in
electrophilic
agent,
highly partners.
15,16
polar 19
same
has
exhibited
medium containing The beneficial
role
a radical
need
was followed hydride
led
suppresses solvent
temperature
on the
III)
chosen
temperature
analysis. being
of
hand,
a small
between
Based
conjugated
reduction
z and E isomers
G.C.
is
first
higher
experiments.
98%
by the
other
There exists
and these
scavenger,
on the
catalyst.
method l4
-0
rate
yield
radical
phosphine,
+ 10.4X 1 + 5.3x
set
product’s
added
correlation
and hydride
modified
the of
palladium
no significant
resulting
as demonstrated
roles
Added triphenyl
temperature of
between
beneficial
rate.
Apparently,
sequence
yield
the
by over-stabilizing
benzene.
ger
correlation
revealed
acting
for
scavenger, the inertness of the benzyl chloride to the reac18 one equivalent of Bu3Snll and the absence of CIDNP effects 21 by NMR, suggest the present hydrogenation to be another rare only
as an hydride
donor.
A plausible
mechanism
involves
palladium
479
Table
II.
Factorial
plane
of
experiments
x2
x3
x4
x5
-
-
+
-
for
reduction
of
8 iononea
W-W Exp. No.
x1
l+-
Yield
xlx2
x1x3
+
+
5.4
(%)
2++--++
-
-
29.6
3+-+--+
-
+
25.7
4
++
+
-
-
-
+
65.8
5+--+-+
+
-
5.6
6++-+--
-
+
21.0
-
4.4
+
+
7.7
7+-+++-a++++++ a)
In each
experiment
and 0.03
a 5 ml solution
mmole Pd(P$3)4
(temperature)
containing
was subjected
to
:
(2,6-di-t-butyl-4-methylphenol):
1 mmole 8 ionone
the
following
rate
(solvent)
Table exp. no.
temp.
of
Bu3SnH):
:
Simplex
III.
optimization
of
23’C
-
0.06
mmole
0.24
mmole
1 mmole/h
6 mmole/h
benzene
THF
8 ionone
reductiona
radical scavenger
solvent/proton source
yield
70.3%
9
4o”
0.48
eq.
benzene
10
60’
0.72
eq.
benzene
11
3o”
0.42
eq.
THF/H20
12
3o”
conditions:
O0
(triphenylphosphine): (addition
-c
29.7% (2.8
THF/H20 2.7
83.8%
eq.) (eq.)/
>98%
NH4C1 (2 eq.) a)
In each solution
catalyzed conditions
hydrostannation to
the
The expected stenone
or even
chemoselectively
parent
experiment
Bu3SnH was added
of
1 mmole f3 ionone
to
form
carbonyl
importance
of
an intermediate 22 compound.
steric
A1’4-cholestadienone reduced
in
and 0.03
excellent
factors to
this
yield:
enol
at
a rate eq.
1 eq./hr
to
a 5 ml
Pd(P$3)4.
stannane
was demonstrated reducing
of
system,
which
by the whereas
decomposes
resistance withanolide
under
protic
of A4-chole23 was D
480
OH OH in situ utilization of the intermediate Further scope and limitation studies, as well as -1 en01 stannane are in progress. AcknowledRement.
We
wish to thank the Sir Charles Clore - Weizmann Fund Post Doctoral Fellow-
ship and the U.S.-Israel Binational Science Foundation for their generous support. References
1) 2) 3)
4) 5)
6)
7) 8) 9) 10) 11)
12) 13) 14) 15) 16)
17) 18) 19) 20) 21) 22) 23)
For early work in this area see: B.M. Trost and E. Keinan, Tetrahedron Lett. 2591, 2595 (1980). a. R.L. Augustine, "Catalytic Hydrogenation", Marcel Dekker, N.Y.C. (1965); b. M.Freifelder, "Catalytic Hydrogenation in Organic Synthesis", Wiley, N.Y. (1978). a. M. Smith in "Reduction", p. 95-170, R.L. Augustine Ed. Marcel Dekker, N.Y.C. (1968); b. A.J. Birch and H. Smith, Q. Rev. Chem. Sot., 12, 17 (1958); c. H.O. House "Modern Synthetic Reactions". D. 173-181. W.A. Beniamin. Menlo Park Ca. (1972). J.P. Collmg, R.G. Finke, P.L. Matlock, R. Wahren, R.G: Kombto and J.I. Brauman, 3. Amer. Chem. Sot., 100, 1119 (1978) and ref. cited therein. a. T. Tsuda, T. Fuhii, K. Kawasaki and T. Saegusa, J. Chem. Sot. Chem. Comm., 1013 (1980); b. E.C. Ashby, J.J. Lin and A.B. Goel, J. Org. Chem., 2, 183 (1978); c. M.F. Semmelhack and R.D. Stauffer, J. Org. Chem., 40, 3619 (1975); d. S. Masamune, G.S. Bates and P.E. Georghiou, J. Amer. Chem. Sot., s, 3686 -974); e. R.K. Baeckman Jr. and R. Michalak, J. Amer. Chem. sot.. 96. 1623 119741. a.1: vima and-T. Kbgure, Tetrahedron Lett., 5085 (1972); b. T. Hayashi, K. Yamamoto and 111. Kurnada,Tetrahedron Lett., 3 (1975); c. A.J. Birch and K.A.M. Walker, J. Chem. Sot.(C) 1894 (1966); d. R.E. Harman, J.L. Parsons, D.W. Cooke, S.K. Gupta and J. Schoolenberg, J. Org. Chem., 34, 3684 (1969); e. J.F. Biellman and M.J. Jung, J. Amer. Chem. Sot., 2, 1673 (1968); f. F.H. Jardine and G. Wilkinson, J. Chem. Sot. (C), 270 (1967); g. J.P.Candlin and A.R. Oldham, Discuss, Faraday Sot., 46, 60, 92 (1968); h. T. Kitamura et al. Chem. Lett., 379 (1973), 203 (1975). a. D.L. Reger, M.M. Habib and D.J. Fauth, J. Org. Chem., 34, 3860 (1980); b. J.Kwiatek, Catal. Rev., 1, 37 (1967); c. R.W. Goetz and M. Orchin, J.xmer. Chem. Sot., E, 2782 (1963). Y. Sasson and J. Blum, J. Org. Chem., 40, 1887 (1975). J. Blum et al., Tetrahedron Lett., 192571981)*. N.A. Cortese and R.F. Heck ,,J. Org. CF., 43, 3985 (1978). a. J. Godschalx and J.K. Stille, Tetr edron Lett., 2599 (1980). Fox-relatedwork see also: b. D.Milstein and J.K. Stille, J. Amer. Chem. Sot., 101, 4981, 4992 (1979), J. Org. Chem., 44, 1613 (1979). E. Keinan and N. Greenspoon, accompanying manuscript in this issue. O.L. Davies Ed., “The design and analysis of industrial experiments", Oliver andEoyd, London (1954). G.E.P. Box and D.W. Behnken, Ann. Math. Statist., 2, 838 (1960). H.G. Kuivila. Svn.. 499 (19701. Non selective conjugate reduction with Bu SnH via a free radical mechanism is reported to require photochemical or thermal (15O'C) snitixon: a. M. Pereyre, G. Colin and J. Valade, Tetrahedron Lett., 4805 (1967); b. M. Pereyre and J. Valade, Tetrahedron Lett., 489 (1969). W.P. Neumann and E. Heymann, Ann., 683, 11, 24 (1965). N.Y.M. Fung, P. DeMayo, J.H. bauble and A.C. Weedon, J. Org. Chem., 9, 3977 (1978) and references cited therein. A.J. Leusink et al., J. Organomet. Chem., 13, 155, 163 (1968). Reduction of an equimolar mixture of benzalacetone and benzyl chloride resulted in quantitative reduction of the first compound and the recovery of the unreacted benzyl chloride. The reaction was followed by 270 MHz NMR, with spectra being recorded every ten seconds. An analogous stepwise conjugate reduction based on rhodium catalyzed hydrosilylation, followed by acid hydrolysis has been reported (see ref. 6a,b), however, lower selectivity was noted (e.g. compare-reductionof 8 ionone). F.W. Eastwood,I. Kirson, D. Lavie and A. Abraham, Phytochem., 19, 1503 (1980).Applfcation of this method to selective transformations in the Withanolide series will be published elsewhere. (Received in UK 20 November 1981)