Communications
CuH, see ref. [5] and Y. Moritani, D. H. Appella, V. Jureakau-
seas, S. L. Buchwald, J. Am. Chem. Soc. 2000, 122, 6797.
[10] N. J. Lawrence, M. D. Drew, S. M. Bushell, J. Chem. Soc. Perkin
Trans. 1 1999, 3381. Although four equivalents of hydride were
used in these experiments, we have since found that only two
equivalents are actually needed.
[11] a) B. H. Lipshutz, K. Noson, W. Chrisman, A. Lower, J. Am.
Chem. Soc. 2003, 125, 8779; b) B. H. Lipshutz, K. Noson, W.
Chrisman, J. Am. Chem. Soc. 2001, 123, 12917.
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Am. Chem. Soc. 2000, 122, 6797. See also, B. H. Lipshutz, J. M.
Servesko, P. Papa, T. Petersen, A. Lover, in preparation.
[13] a) S-(À)-BITIANP: T. Benincori, E. Brenna, F. Sannicolo, L.
Trimarco, P. Antognazza, E. Cesarotti, F. Demartin, T. Pilati,J.
Org. Chem. 1996, 61, 6244; b) R,S-(À)-BoPhoz: N. W. Boaz,
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7 h).
prochiral enones provides access to compounds with highly
stereodefined centers b to acyclic ketones. Reliance on
catalytic quantities of a base metal in the form of CuH,
along with readily available nonracemic ferrocenyl ligands
and inexpensive PMHS as the stoichiometric source of
hydride, all combine to offer an exceedingly mild and
straighforward procedure.[18] New technologies utilizing this
initial CuH-based 1,4-reduction/transmetalation protocol but
which rely on boranes[19] (in place of silanes), thereby
providing entries to subsequent aldol reactions, a-arylations,
etc., will be reported in due course.
Received: July 4, 2003 [Z52313]
Published Online: September 23, 2003
Keywords: conjugate reductions · copper hydride · enones ·
.
hydrosilylation · phosphane ligands
[14] a) A. Togni, C. Breutel, A. Schnyder, F. Spindler, H. Landert, A.
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[15] Product S-9 gave a negative rotation ([a]25406 = À6.0 (c = 1.8,
CHCl3), whereas R-9 gave an equal and opposite (positive)
rotation, as expected for these known compounds; cf. G. Bram,
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[18] Represenative procedure (Table 3, entry 2): To a 5-mL round-
bottom flask flame-dried and purged with argon was added
CuH·PPh3 (2 mg, 0.006 mmol) and ligand ent-B (5.42 mg,
0.003 mmol). Toluene (0.3 mL) was added and the solution
cooled to À788C. PMHS (78 mL, 1.21 mmol) was introduced
dropwise by syringe and then the enone was added (neat; 82 mg,
0.304 mmol). The reaction mixture was stirred for 6 h at À788C
until the reaction was complete by TLC (2% Et2O:ligroin). It
was then quenched at À788C with 3m NaOH, warmed to room
temperature, diluted with Et2O/H2O, and stirred for 2 h. The
aqueous layer was extracted twice with Et2O, and the combined
organic layers were washed with brine, dried over anhydrous
MgSO4, filtered, and concentrated by rotary evaporation. The
residue was purified by flash chromatography (2% Et2O:ligroin)
to afford the product ketone (78 mg, 95%) as a clear oil. The
product (Rf = 0.27, 10% Et2O/ligroin) was analyzed by chiral
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~
GC (BDM 110) which indicated an ee of 98%. IR (neat): n =
2929, 1718, 1255, 1097, 835, 774 cmÀ1 1H NMR (400 MHz,
;
[6] Due to the lack of any suitable means of effecting such
asymmetric conjugate reductions, this strategy is usually not
even considered an option for the control of stereochemistry at a
site b to a ketone.[1] For early hydrogenation studies on enones
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C6D6): d = 0.08 (s, 6H), 0.82 (d, J = 6.4 Hz, 3H), 1.00 (s, 9H),
1.14–1.24 (m, 2H), 1.24–1.37 (m, 2H), 1.43 (m, 2H), 1.66 (s, 3H),
1.80 (dd, J = 17.5, 6.8 Hz, 1H), 1.95 (m, 1H), 1.98 (dd, J = 17.5,
5.7 Hz, 1H), 3.54 ppm (t, J = 6.1 Hz, 2H); EIMS: m/z (%): 215
(40) [M+ÀBu], 171 (64), 115 (29), 75 (100); HR-EIMS calcd for
C15H32O2Si·C4H9: 215.1467; found 215.1470. Additional data for
all new compounds can be found in the Supporting Information.
[19] B. H. Lipshutz, P. Papa,Angew. Chem. 2002, 114, 4762; Angew.
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Am. Chem. Soc. 1989, 111, 8818. c) For in situ generation of
4792
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2003, 42, 4789 –4792