TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 1313–1321 Pergamon Chiral aminoalcohols with a menthane skeleton as catalysts for the enantioselective addition of diethylzinc to benzaldehyde † Stefan Panev, a Anthony Linden b and Vladimir Dimitrov a, * a Institute of Organic Chemistry, Bulgarian Academy of Sciences, BG -1113 Sofia, Bulgaria b Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland Received 17 April 2001; accepted 8 May 2001 Abstract—Novel chiral aminoalcohols were synthesized by highly diastereoselective addition of Me 3 SiCN and LiCH 2 CN to (-)-menthone followed by LiAlH 4 reduction. The addition of CH 2 CH-MgBr and PhCHCH-MgBr to menthone and the following epoxidation, provided useful hydroxy epoxides, one of which could be aminolyzed to afford an aminodiol. In one case, the configuration of the newly formed epoxidic stereogenic center was determined by X-ray crystallography. When applied as catalysts in the enantioselective addition of Et 2 Zn to benzaldehyde, the aminoalcohols induced enantiomeric excesses (e.e.s) of up to 77%. © 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction Catalytic asymmetric carboncarbon bond formation has been one of the most studied fields in synthetic organic chemistry over recent years. 1–3 The enantiose- lective addition of dialkylzinc compounds to aldehydes in reactions catalyzed by different types of chiral lig- ands has been investigated intensively because the preparation of enantiomerically pure or enriched alco- hols is of considerable interest for the synthesis of bioactive compounds and natural products. 4 Aminoal- cohols have been shown to be highly efficient chiral catalysts and among them the -aminoalcohols have been thought to provide the best results. In general, since Noyori demonstrated the high activity of (-)-3- exo -dimethylaminoisoborneol and suggested a mecha- nistic model for the catalytic cycle, -aminoalcohols have usually been employed. 5 Until recently, only a few examples of the use of - 6 and -aminoalcohols 7,8 have been reported. However, there has been increased inter- est in the preparation of -aminoalcohols, and their utility as catalysts for the asymmetric addition of dialkylzincs to aldehydes has been demonstrated. 9 The -aminoalcohol N,N -dimethylaminopropyl neomen- thol, 8 prepared in one step by the addition of dimethyl- aminopropyl lithium to (-)-menthone, catalyzed the enantioselective addition of diethylzinc to several alde- hydes with excellent enantioselectivities of up to 95%. We were therefore interested in preparing (-)-menthone derived - and -aminoalcohols and testing them as chiral ligands. The synthetic strategy used for the study presented herein was developed during recent investigations. 10 This strategy involves the addition of suitable organometallic reagents to (-)-menthone, which pro- ceeds highly diastereoselectively, 11 and further transfor- mation of the products to afford the desired aminoalcohols. 2. Results and discussion The first step in the investigation was, based on previ- ous experiences, 10 the addition of Me 3 SiCN, LiCH 2 CN, CH 2 CH-MgBr and PhCHCH-MgBr to (-)-men- thone. For a successful reaction with Me 3 SiCN, the (-)-menthone 1 needed to be activated with an equimo- lar quantity of BF 3 ·OEt 2 . Interestingly, the attack of the reagent occurred predominantly from the axial face of the menthane skeleton leading to the axial and equatorial addition products presented in Scheme 1. In the case of the equatorial addition product, it was not possible during the hydrolytic work-up to cleave com- pletely the initially formed silyl ether 3, to give the corresponding cyanohydrin 2 (ratio 2:3:4=20:11:69 in * Corresponding author. E-mail: vdim@orgchm.bas.bg † Dedicated to Professor Heinz Heimgartner on the occasion of his 60th birthday. 0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(01)00206-3