Conjugate reduction of α,β-unsaturated ketones using an Mn(III) catalyst, phenylsilane and isopropyl alcohol

Article abstract of DOI:10.1016/S0040-4039(00)01728-7

Treatment of a variety of α,β-unsaturated ketones with Mn(dpm)₃ (3 mol%)/PhSiH₃ (1.3 equiv.)/isopropyl alcohol with the exclusion of air resulted in the formation of the saturated ketone. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01728-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9731–9733
Conjugate reduction of a,b-unsaturated ketones using an
III
Mn catalyst, phenylsilane and isopropyl alcohol
Philip Magnus,* Michael J. Waring and David A. Scott
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
Received 7 August 2000; revised 25 September 2000; accepted 28 September 2000
Abstract
Treatment of a variety of a,b-unsaturated ketones with Mn(dpm) (3 mol%)/PhSiH (1.3 equiv.)/iso-
3
3
propyl alcohol with the exclusion of air resulted in the formation of the saturated ketone. © 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: reduction; conjugate; manganese; phenylsilane.
In the accompanying letter we reported the conjugate reduction of a,b-unsaturated ketones
followed by oxidation of in situ generated enolates to give a-hydroxyketones using
1
Mn(dpm) (cat)/PhSiH /O /i-PrOH. In this letter the application of this reagent system (minus
3
3
2
2
O ) to the conjugate reduction of a,b-unsaturated ketones is reported.
2
In a stoichiometric reaction a dark olive-green solution of Mn(dpm) in i-PrOH at 23°C was
3
treated with PhSiH to give a pale yellow solution, which rapidly reduced 5 to give 6. When the
3
same reaction was conducted with catalytic amounts of Mn(dpm) (3 mol%) the reduction was
3
much slower but proceeded in good yields. Table 1 lists a series of enones that were
conjugatively reduced using this procedure.
Deuterium labeling experiments using PhSiD converted 11 (Scheme 1) into 12d with the
3
incorporation of one deuterium atom in the b-position. This demonstrates that the hydride
III
addition is irreversible since if a putative Mn enolate 12a could b-eliminate HMn(dpm)2
(
isotope effect) one would expect to accumulate 12b which would be converted into the
b,b-dideuterium derivative 12c. Similarly, treatment of 5 with Mn(dpm) /PhSiD gave 6 with
3
3
incorporation of one deuterium atom. Attempts to increase the rate of reduction of 5 by
conducting the reaction at slightly higher temperatures than 23°C did not work and also lead to
3
small amounts of 1,2-reduction to give 4-hydroxyisophorone. The use of alcohols other than
isopropyl alcohol was not productive. For example, if methanol is substituted for isopropyl
*
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01728-7

9732
Table 1
Entry Substrate
Conditions
Product
Yield
50%
1
Me
Mn(dpm) (3 mol%), PhSiH (2 equiv.),
Me
3
3
O
i-PrOH (0.2 M conc of 1)
O
Me
Me
1
2
2
Me
Mn(dpm) (3 mol%), PhSiH (1.3 equiv.),
i-PrOH/DCE
Me
99%
3
3
O
O
H
H
H
H
H
H
H
O
O
O
3
4
3
4
5
Me
As above
As above
99%
25%
50%
Me
O
O
Me
O
Me
Me
Me
5
6
Me
O
Me
O
Me
Me
Me
O
Me
O
Me
Me
7
8
As above
As above
Ph
Ph
9
10
O
6
7
O
74%
Me
Me
Me
Me
4
4
1
2
11
Me
Mn(dpm) (3 mol%), PhSiH (1.3 equiv.),
Me
100%
3
3
i-PrOH/DCM (1:4)
O
O
O
O
OTr 13
OTr1
OTBS
4
8
OTBS
As above
100%
Me
Me
O
O
Me
O
Me
O
OTr 15
OTr1
6
alcohol there was rapid gas evolution (H ), no reduction of 5, and the formation of
2
4
PhSi(OMe) . If the proton source is t-BuOH the reduction proceeds very slowly, consequently
3
i-PrOH is the preferred (optimal) alcohol. The use of other hydride sources was briefly

9733
examined, and it was found that Ph SiH was very slow, Et SiH did not work and polymethyl-
2
2
3
hydrosiloxane was also very slow and incomplete.
(
dpm)2Mn
O
O
D
O
D
D
O
Me
3
Mn(dpm) /PhSiD3
Me
Me
Me
Me
Me
Me
Me
4
i-PrOH
4
4
4
D
11
12a
12b
12c
Me
Me
O
D
O
O
D
O
Mn(dpm) /PhSiD3
3
Me
Me
i-PrOH
O
Me
Me
4
Me
Me
1
2d
5
6
Scheme 1.
As expected from the results described in the accompanying paper, b,b-disubstituted a,b-
unsaturated ketones (and esters) are not conjugatively reduced using the above conditions.
Acknowledgements
The National Institutes of Health (GM 32718), The Robert A. Welch Foundation, Merck
Research Laboratories and Novartis are thanked for their support of this research.
References
1
2
. Magnus, P.; Payne, A. H.; Waring, M. J.; Scott, D. A.; Lynch, V. Tetrahedron Lett. 2000, 41, 9725.
. A number of methods have been reported in the literature to accomplish this transformation.
Conjugate reduction using Na(MeOCH CH O) AlH /CuBr: Semmelhack, M. F.; Stauffer, R. D.; Yamashita, A.
2
2
2
2
J. Org. Chem. 1977, 42, 3180. [(Ph P)CuH] : Mahoney, W. S.; Brestensky, D. M.; Stryker, J. M. J. Am. Chem. Soc.
3
6
1
988, 110, 291. [(Ph P)CuH] (cat)/n-Bu SnH or PhSiH : Lipshutz, B. H.; Keith, J.; Papa, P.; Vivian, R.
3 6 3 3
Tetrahedron Lett. 1998, 39, 4627. PhSiH /Mo(CO) (cat): Keinan, E.; Perez, D. J. Org. Chem. 1987, 52, 2576.
3
6
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4
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