Synthesis of Enantiopure (rS,S)- or (rR,S)--Amino Alcohols by Complete Regioselective Opening of Aminoepoxides by Organolithium Reagents LiAlH 4 or LiAlD 4 Jose ´ M. Concello ´n,* Pablo L. Bernad, Virginia del Solar, and Jose ´ Ramo ´n Sua ´rez Departamento de Quı ´mica Orga ´ nica e Inorga ´ nica, Facultad de Quı ´mica, UniVersidad de OViedo, Julia ´ n ClaVerı ´a, 8, 33071 OViedo, Spain Santiago Garcı ´a-Granda and M. Rosario Dı ´az Departamento de Quı ´mica Fı ´sica y Analı ´tica, Facultad de Quı ´mica, UniVersidad de OViedo, Julia ´ n ClaVerı ´a, 8, 33071 OViedo, Spain jmcg@fq.unioVi.es ReceiVed March 29, 2006 The reaction of chiral (2R,1′S)- or (2S,1′S)-2-(1-aminoalkyl)epoxides, 1 or 2 with a variety of organolithium compounds to obtain the corresponding (RS,S)- or (RR,S)- -amino alcohols in enantiopure form is reported. In both cases, the opening of the oxirane ring at C-3 proceeded with total regioselectivity. Moreover, the ring opening of aminoepoxides 1 or 2 by hydride (utilizing LiAlH 4 ) to obtain the corresponding (2S,3S)- or (2R,3S)-3-aminoalkan-2-ols is also described. The reaction of 1 or 2 with LiAlD 4 in place of LiAlH 4 gave the corresponding (2S,3S)- or (2R,3S)-3-amino-1-deuterioalkan-2-ols. Introduction Enantiopure -aminoalkanols are important building blocks and have been used to prepare a large number of biologically active natural and synthetic compounds, 1 including unnatural amino acids. 2 The former compounds have also been used as chiral auxiliaries for asymmetric synthesis. 3 Consequently, a large number of syntheses of enantiopure -amino alcohols have been published. The most common and practical method for the synthesis of these compounds was the direct aminolysis of epoxides. 4 The opening of oxiranes by amines was limited by the high temperature, long reaction time, and excess of amine required. In addition, often the method failed when poorly nucleophilic amines or sterically crowded amines or epoxides were used. Finally, the total control of regioselectivity of the ring opening was, generally, unresolved. For this reason, a general synthesis of enantiopure -amino alcohols with complete selectivity, in which several enantiopure diastereoisomers could be available, would be still desirable. Previously, we reported the efficient synthesis of both enantiopure (2R,1′S)- or (2S,1′S)-2-(1-aminoalkyl)epoxides 1 or 2 by total stereoselective reduction of enantiopure R-amino-R′- chloroketones with LiAlH 4 or by highly stereoselective addition reaction of iodomethyllithium to R-aminoaldehydes, respec- tively. 5 Building on these results, we described, more recently, (1) (a) Corey, E. J.; Zhang, F. Angew. Chem., Int. Ed. Engl. 1999, 38, 1931-1934. (b) Johannes, C. W.; Visser, M. S.; Weatherhead, G. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 8340-8347. (c) Chang, B. L.; Ganesan, A. Bioorg. Med. Chem. Lett. 1997, 7, 1511-1514. (d) Rogers, G. A.; Parsons, S. M.; Anderson, D. S.; Nilson, L. M.; Bahr, B. A.; Kornreich, W. D.; Kaufman, R.; Jacobs, R. S.; Kirtman, B. J. Med. Chem. 1989, 32, 1217-1230. (2) (a) O’Brien, P. Angew. Chem., Int. Ed. 1999, 38, 326-329. (b) Li, G.; Chang, H. T.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1996, 35, 451-454. (3) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835- 875. (4) (a) Hodgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron 1996, 52, 14361-14384. (b) Bergmeier, S. C. Tetrahedron 2000, 56, 2561-2576. (d) Hanson, R. M. Chem. ReV. 1991, 91, 437-476. 6420 J. Org. Chem. 2006, 71, 6420-6426 10.1021/jo0606756 CCC: $33.50 © 2006 American Chemical Society Published on Web 07/26/2006