I. Kamiya, A. Ogawa / Tetrahedron Letters 43 (2002) 1701–1703
1703
due to the steric repulsion with substrates.14 The
present reduction of cyclic ketones proceeded almost
quantitatively, and their stereoselectivities indicated
similar trends as the LiAlH4- and NaBH4-reduction.
drawing group. In these cases, we examined the transi-
tion-metal-catalyzed reduction in the presence of
Galvinoxyl as a radical inhibitor at lower temperature
(0°C), because these conditions suppress the radical
reduction effectively (see entries 7–9 in Table 1).
In conclusion, we have developed the first example of
9. The following is a general method for the palladium-cata-
lyzed reduction of ketones: Di-n-butyltin dihydride
palladium-catalyzed
reduction
with
nBu2SnH2.
n
(nBu2SnH2) was prepared by the reduction of Bu2SnCl2
Although the transition-metal-catalyzed reduction of
n
ketones with Bu3SnH does not take place at all, the
(82 mmol) with LiAlH4 (62 mmol) in diethyl ether (100
mL) at 40°C for 4 h, and was purified by distillation
under reduced pressure (bp 55°C/7 mmHg).7 Toluene was
purified by distillation from calcium hydride (CaH2). All
reactions were carried out in a flame-dried two-necked
flask in the dark under an atmosphere of nitrogen with
magnetic stirring. nBu2SnH2 (2 mmol) was added drop-
wise over 2 h via a syringe to a solution of substrate (1
mmol) and Pd(PPh3)4 (1 mol%=0.01 mmol) in toluene (1
mL) at room temperature (or 0°C). After the reaction
mixture was stirred for 1 h, toluene was removed under
reduced pressure. Purification of the product was carried
out by using a recycling preparative HPLC (Japan Ana-
lytical Industry Co. Ltd., model LC-908) equipped with
JAIGEL-1H and -2H columns (GPC) using CHCl3 as an
eluent.
n
use of Bu2SnH2 in the palladium-catalyzed reduction
system makes it possible to reduce various ketones.
Further investigations to clarify the precise reaction
pathway are now in progress.
Acknowledgements
We thank Ms. Atsuko Kudo for her contribution to
this work at the initial stage. Financial support of this
work by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Sports and Culture, Japan is
gratefully acknowledged.
n
10. In the presence of palladium catalyst, Bu2SnH2 is easily
References
decomposed to di-(or oligo-) stannane and molecular
hydrogen. To suppress this side reaction, the palladium-
catalyzed reduction of ketones requires the use of excess
nBu2SnH2 (1.5–2.0 equiv.) and the slowly dropping of
nBu2SnH2.
1. Pereyre, M.; Quintard, J.-P.; Ralhm, A. Tin in Organic
Synthesis; Butterworths: London, 1987.
2. Harrison, P. G. Chemistry of Tin; Blackie & Son: New
York, 1989.
3. Davies, A. G. Organotin Chemistry; VCH: Weinheim,
1997.
4. Four, P.; Guibe, F. J. Org. Chem. 1981, 46, 4439.
5. (a) Kuniyasu, H.; Ogawa, A.; Sonoda, N. Tetrahedron
Lett. 1993, 34, 2491; (b) Kuniyasu, H.; Ogawa, A.;
Higaki, K.; Sonoda, N. Organometallics 1992, 11, 3937.
6. Keinan, E.; Gleize, P. A. Tetrahedron Lett. 1982, 23, 477.
7. Ferkous, F.; Messadi, D.; De Jeso, B.; Degueil-Castaing,
M.; Maillard, B. J. Organomet. Chem. 1991, 420, 315.
8. A trace amount of oxygen contaminated in the reduction
system sometimes induces the radical reduction with
nBu2SnH2, of some ketones bearing an electron-with-
11. Pd(PPh3)4-catalyzed reduction of a,b-unsaturated ketones
n
with Bu3SnH in more polar solvents such as THF in the
presence of proton sources is reported to provide the
corresponding saturated ketones (see Ref. 6).
12. (a) Bowry, V. W.; Lusztyk, J.; Ingold, K. U. J. Am.
Chem. Soc. 1991, 113, 5687; (b) Bowry, V. W.; Ingold, K.
U. J. Am. Chem. Soc. 1991, 113, 5699.
13. (a) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron
Lett. 1968, 2205; (b) Cherest, M.; Felkin, H. Tetrahedron
Lett. 1971, 383.
14. Krishnamurthy, S.; Brown, H. C. J. Am. Chem. Soc.
1976, 98, 3383.