TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 14 (2003) 1463–1466 Pergamon Asymmetric reduction of ketoxime derivatives and N -alkylketimines with borane–oxazaborolidine adducts Marek P. Krzemin ´ ski and Marek Zaidlewicz* Department of Chemistry, Nicolaus Copernicus University, 87 -100 Torun ´ , Poland Received 13 February 2003; accepted 7 April 2003 Abstract—Oxime ethers of acetophenone, isopropyl methyl ketone, and tert -butyl methyl ketone were reduced to the correspond- ing hydroxylamine ethers of 45–94% ee with borane–oxazaborolidine 1 derived from (-)-norephedrine. A one-pot reduction of acetophenone oxime with 1 to 1-phenylethylhydroxylamine of 87% ee is described. The reduction of 6-methyl-2,3,4,5-tetra- hydropyridine and N-methylimines of the above mentioned ketones with borane-B -methyloxazaborolidine adduct 2, derived from (-)-diphenylprolinol, gave the corresponding amines of 40–74% ee. © 2003 Elsevier Science Ltd. All rights reserved. In contrast to excellent reagents and catalysts devel- oped for the asymmetric reduction of prochiral ketones, limited success has been achieved in the reduction of prochiral ketoximes and ketimines. 1 Boranes and boro- hydrides are among the reagents of choice for these reductions. 2 Although many years ago it was reported that the reduction of oximes can be controlled to produce hydroxylamines, 3 only recently, in connection with the synthesis of 5-lipoxygenase inhibitor, has the asymmetric reduction of 7-benzyloxycumaranone oxime O -benzyl ether with borane–oxazaborolidine adduct 1 derived from (-)-norephedrine, been achieved. 4a The reaction depends on the ether group as indicated by unreactive hindered ethers, and mixtures of products obtained from O -methoxymethyl and allyl ethers. 4b However, its scope has not been delineated. Also, little is known on the asymmetric reduction of N -alkylket- imines with boranes. The small amount of reported data show low to moderate enantioselectivity. 5 Conse- quently, in continuation of our earlier studies on the reduction of oximes, 6 we decided to examine the asym- metric reduction of representative ketoxime derivatives and N -alkylketimines with borane-oxazaborolidine adducts 1–3. The adducts 1 and 3 are prepared in tetrahydrofuran and used in situ, 2a,4b,7 whereas 2 is a stable crystalline compound, and can be used in other solvents (Fig. 1). 8 Acetophenone oxime O -methyl ether 4a, isopropyl methyl ketone oxime O -methyl ether 5a, and tert -butyl methyl ketone oxime O -methyl ether 6a were reduced with 1. The reaction run in tetrahydrofuran at 0°C afforded mixtures of the corresponding hydroxylamine O -methyl ethers and amines of 45–82% ee in 31–92% yield (Table 1). The products were readily separated by flash chromatography. Enantiomeric excesses of the hydroxylamine ethers and amine products are the same, since the amines are formed by the reduction of hydroxylamine ethers not affecting the stereogenic cen- tre. The reduction of 4a proceeded in a high yield to give a mixture of 1-phenylethylhydroxylamine O - methyl ether 7a and 1-phenylethylamine 10 of 55% ee in a 54:46 ratio. Oxime ethers 5a and 6a were reduced with 1 to the corresponding hydroxylamine O -methyl ethers 8a and 9a with higher chemoselectivity, 87 and 77%, respectively. Enantioselectivity increased to 82% ee for 8a, but decreased to 45% ee for the more hindered 9a. The reduction of O -benzyl ether 4b with 1 showed higher chemo- (77%) and enantioselectivity (94% ee) as compared with 4a, whereas a slight decrease in selectiv- Figure 1. * Corresponding author. Tel.: (+4856) 6114522; fax: (+4856) 6542477; e-mail: zaidlevi@chem.uni.torun.pl 0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0957-4166(03)00314-8