Acceleration of the reduction of aldehydes and ketones using Mn(dpm)3 catalyst and phenylsilane in the presence of dioxygen

Article abstract of DOI:10.1016/S0040-4039(01)01304-1

Saturated ketones and aldehydes are reduced to alcohols by phenylsilane and Mn(dpm)₃(cat) in the presence of dioxygen.

Full text of DOI:10.1016/S0040-4039(01)01304-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6633–6636
Acceleration of the reduction of aldehydes and ketones using
Mn(dpm)3 catalyst and phenylsilane in the presence of dioxygen
Philip Magnus* and Mark R. Fielding
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
Received 3 July 2001; revised 17 July 2001; accepted 19 July 2001
Abstract—Saturated ketones and aldehydes are reduced to alcohols by phenylsilane and Mn(dpm)3(cat) in the presence of
dioxygen. © 2001 Elsevier Science Ltd. All rights reserved.
These observations prompted the interesting notion
of whether the hydridic reagent 2 would be unreactive
towards saturated carbonyl groups, but when ‘acti-
vated’ by dioxygen (to give 3) be capable of reducing
the carbonyl group to a secondary alcohol.
Recently, we reported that tris(dipivaloylmethanato)-
manganese(III) 1 (Eq. (1)) [abbreviated to Mn(dpm)3]-
(cat), phenylsilane and dioxygen, in 2-propanol at 0°C,
converted a,b-unsaturated ketones into a-hydroxy
ketones.1 In the absence of dioxygen, conjugate reduc-
tion to the saturated ketone is the major reaction
pathway.2 We observed that 1 reacts with PhSiH3 in the
presence of 2-propanol to give a weakly hydridic reduc-
ing agent formulated as 2 (or equivalent with SiPhH2
attached to Mn).
Treatment of 4-tert-butylcyclohexanone (entry 1, Table
1) in 2-propanol/1,2-dichloroethane (DCE) containing
Mn(dpm)3 (3 mol%) under an oxygen atmosphere at
3O2
PhSiH3/CH2Cl2
HMnO2(dpm)2
HOOMn(dpm)2
HMn(dpm)2
Mn(dpm)3
(1)
No reaction until
i-PrOH is added
1
2
3
4
25°C with phenylsilane, resulted in rapid (5 min) reduc-
tion to the corresponding alcohol as a 14:1 trans:cis
mixture of stereoisomers in 98% yield.4 Conducting the
same procedure, but excluding oxygen, resulted in rela-
tively slow (4 h) conversion into the alcohol (80%
conversion, 57% isolated yield).
During the course of this work we observed that in the
presence of dioxygen the putative manganese hydride
species was more ‘hydridic’ and was able to conjuga-
tively reduce a,b-unsaturated enones, esters and nitriles
that were unreactive when dioxygen was excluded. The
uptake of dioxygen that converts 2 into 3 is reversible,
and over a period of about 3 h at 25°C 3 is transformed
into a non-hydridic species that we suggest is 4.3 It was
found that 5 was inert to conjugate reduction in the
absence of oxygen, whereas in the presence of oxygen,
5 was converted into 6 (Scheme 1).1
Table 1 lists a number of substrates that have been
exposed to the above reduction conditions. In general
entries 2, 3, 4 and 13 show a marked preference for
reduction to the more stable equatorial alcohol, in
keeping with the Felkin model for cyclic ketones.5
Me
Me
Me
OH
Mn(dpm)3
Mn(dpm)3
No reaction
PhSiH3/CH2Cl2/i-PrOH
PhSiH3/CH2Cl2/i-PrOH
Me
O
O
Me
Me
O2
5
6
Scheme 1.
Keywords: tris(dipivaloylmethanato)manganese(III); dioxygen; hydridic.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01304-1

6634
P. Magnus, M. R. Fielding / Tetrahedron Letters 42 (2001) 6633–6636
Table 1.
Substrate
Product(s)
Yield (ratio)
1
98% (14:1, trans:cis)
HO
O
But
Me
But
Me
Ref. 7
2
84% (13:1, trans:cis)
87% (2.1:1, trans:cis)
HO
O
Ref. 8
3
HO
O
Me
Me
Ref. 1
4
81% (1:9, trans:cis)
HO
Me
O
Me
Ref. 1
5
92%
HO
O
O
O
O
O
6
Only trace amounts of reduction was
observed by 1H NMR
Me
Me
Me
O
7
Only trace amounts of reduction was
observed by 1H NMR
Me
Me
Me
O
8
58% (14:1, endo:exo) 5% SM
53% (1:7, endo:exo) 31% SM
OH
O
Ref. 9
Me
9
Me
Me
Me
OH
O
Ref. 10
10
11
22%, 75% SM
13%, 85% SM
O
O
HO
HO

P. Magnus, M. R. Fielding / Tetrahedron Letters 42 (2001) 6633–6636
6635
Table 1. (Continued)
Substrate
Product(s)
Yield (ratio)
99%
12
HO
O
Ref. 11
13
92%, (35:1, 3b:3a)
C8H17
HO
H
H
H
H
Ref. 12
O
H
OH
14
47%, 37% SM, and some O-silylated product.
(mass balance)
O
H
H
H
H
Ref. 13
HO
H
OH
15
61%, 20% SM, and some O-silylated product
(mass balance)
O
H
H
H
H
Ref. 14
MeO
16
17
43%, and some O-silylated product (mass
balance)
O
OH
n-C6H13
C6H13-n
n-C6H13
C6H13-n
85%, both products shown, and diols
Me
Me
HO
Me
O
O
Me
OH
Me
O
Me
O
Me
Me
Me
Ref. 15
18
19
20
24%, by 1H NMR
OH
O
O
Ph
Me
Ph
Ph
Me
NR
Ph
80%
CH2OH
CH2OH
CHO
CHO
O2N
O2N
21
56%
MeO
MeO

6636
P. Magnus, M. R. Fielding / Tetrahedron Letters 42 (2001) 6633–6636
Table 1. (Continued)
Substrate
Product(s)
Yield (ratio)
68%
22
CHO
CH2OH
23
92%
CH2OH
CHO
The yields refer to isolated products unless otherwise stated. All reactions were run under the same conditions except entry 15, where a 1:1 ratio
of 2-propanol:1,2-dichloroethane was employed to dissolve the substrate.
Semmelhack has also reported that Et3SiH/Ru(II)/
AgOCOCF3 reduces 4-tert-butylcyclohexanone to give
the equatorial alcohol as the major stereoisomer (95:5).6
Lett. 2001, 42, 4127; (c) Inoki, S.; Kato, K.; Isayama, S.;
Mukaiyama, T. Chem. Lett. 1990, 1869.
2. Magnus, P.; Waring, M. J.; Scott, D. A. Tetrahedron
Lett. 2000, 41, 9731.
Hindered ketones (entries 6, 7, 8, 9, 14, 15 and 16) are
less reactive, and where stereoselectivity issues arise the
major alcohol results from reduction from the least
encumbered face of the carbonyl group. Medium ring
ketones (entries 10 and 11) are also less reactive. Car-
bonyl groups conjugated with an aromatic ring are only
slowly reduced, and aromatic aldehydes (entries 20, 21
and 22) were surprisingly (relative to entry 23) slow to
reduce.
3. (a) James, B. R.; Ng, F. T. T.; Rempel, G. L. Can. J.
Chem. 1969, 47, 4521; (b) Osborn, J. A.; Powell, A. R.;
Wilkinson, G. Chem. Commun. 1966, 461; (c) Roberts, H.
L.; Symes, W. R. J. Chem. Soc. (A) 1968, 1450; (d)
Lawson, D. N.; Mays, M. J.; Wilkinson, G. J. Chem.
Soc. (A) 1966, 52. All of these papers describe the forma-
tion of RhOOH from RhH in the presence of dioxygen.
4. Greeves, N. In Comprehensive Organic Synthesis; Trost,
B. M.; Fleming, I., Eds.; Pergamon Press, 1991; Vol. 8.
5. (a) Che´rest, M.; Felkin Tetrahedron Lett. 1968, 2205; (b)
Wu, Y.-D.; Houk, K. N. J. Am. Chem. Soc. 1987, 109,
908; (c) Mukherjee, D.; Wu, Y.-D.; Fronczek, F. R.;
Houk, K. N. J. Am. Chem. Soc. 1988, 110, 3328; (d)
Huet, J.; Maroni-Barnaud, Y.; Anh, N. T.; Seyden-
Penne, J. Tetrahedron Lett. 1976, 159.
Representative procedure: Phenylsilane (348 mL, 0.4
equiv.) was added dropwise to a stirred solution of the
substrate (2 mmol) and Mn(dpm)3 (36 mg, 3 mol%) in
2-propanol (2 mL)/1,2-dichloroethane (100 mL) under
an oxygen atmosphere (1 Atm) at 23°C. On completion
of the reaction (TLC), the mixture was evaporated to
dryness and the residue purified by chromatography
over silica gel eluting with EtOAc/pentane mixtures to
give the corresponding alcohol.
6. Semmelhack, M. F.; Misra, R. N. J. Org. Chem. 1982,
47, 2469.
7. Kartha, G.; Go, K. T.; Bose, A. K.; Tibbetts, M. S. J.
Chem. Soc., Perkin Trans. 2 1976, 717.
8. Kobayashi, Y.; Takahisa, E.; Nakano, M.; Watatani, K.
Tetrahedron 1997, 53, 1627.
9. Stoffers, J. B.; Tan, C. T.; Teo, K. C. Can. J. Chem. 1976,
54, 1211.
In summary, the above reduction procedure provides a
mild method that does not need exclusion of air or
moisture.
10. Coxon, J. M.; Hydes, G. S.; Steel, P. J. J. Chem. Soc.,
Perkin Trans. 2 1984, 1351.
11. Loomes, D. J.; Robinson, M. J. T. Tetrahedron 1977, 33,
1149.
Acknowledgements
12. Malinowski, E. R.; Manhas, M. S.; Mu¨ller, G. H.; Bose,
A. K. Tetrahedron Lett. 1963, 1161.
13. McDermott, I. R.; Robinson, C. H.; Deklerk, D. P.
Steroids 1978, 31, 511.
14. Kametani, T.; Matsumoto, H.; Nemoto, H.; Fukumoto,
K. J. Am. Chem. Soc. 1978, 100, 6218.
The National Institutes of Health (GM 32718), The
Robert A. Welch Foundation, Merck Research Labo-
ratories and Novartis are thanked for their support of
this research.
15. (a) Khare, A.; Moss, G. P.; Weedon, B. C. L. J. Chem.
Soc., Perkin Trans. 2 1988, 1389; (b) Tanaka, A.;
Yamamoto, H.; Oritani, T. Tetrahedron: Asymmetry
1995, 6, 1273; (c) Lamb, N.; Abrams, S. R. Can. J. Chem.
1990, 68, 1151.
References
1. (a) Magnus, P.; Payne, A. H.; Waring, M. J.; Scott, D.
A.; Lynch, V. Tetrahedron Lett. 2000, 41, 9725; (b)
Magnus, P.; Scott, D. A.; Fielding, M. R. Tetrahedron