Starting from chiral glycol aldehyde hydrazones (S)-2, we sive introduction of two vicinal stereogenic centres opens a prepared differently protected a-hydroxy aldehydes ( R ) -or new, flexible syn-diastereo-and enantioselective route to (S)-4 as well as N-acetyl-protected 1,2-amino alcohols (R)-11 functionalised, N-acetyl-protected, vicinal amino alcohols in high enantiomeric excesses via azaenolate a-alkylation or (R,R)-13, which was demonstrated in the case of the y-aminonucleophilic 1,2-addition to the CN double bond. The succes-P-hydroxycarboxylic acid statin (R,R)-15 and its analogues B.1,2-Amino alcohols A are important substructures of many natural products and drugs, such as unusual amino acids, amino sugars, alkaloids, sphingolipids, and antibiotics [']. Furthermore, diastereo-and enantiomerically pure amino alcohols are becoming increasingly important in the development of enzyme inhibitors by peptide mimeticsL21. Pharmacologically interesting examples are the yamino-P-hydroxycarboxylic acids of type B, such as statin (R = iBu), 3-amino-2-hydroxy-5-phenylpentanoic acid (AHPPA, R = Bzl) and the analogous cyclohexylstatin (R = CH2C6Hll). Statin[lc.e], and AHPPA are key units of pepstatinL3I and aphatininF4], both natural peptidic inhibitors of acidic proteases, e.g. renin or HIV-I protease. The stereoselective syntheses of 1,2-amino alcohols described in the literature so far normally start from naturally occurring amino acids ("ex chiral p00l")[~I. Because of the demand for new, efficient, and highly stereoselective methods for these compounds, asymmetric syntheses are becoming more and more importantr5].Another interesting class of bifunctional molecules bearing a protected hydroxyl group are a-hydroxy aldehydes C. These are again important building blocks for the synthesis of natural products and bioactive c o m p~u n d s [~~~] . Another domain of research has been the development of diastereoselective reactions of the aldehyde group, e.g. 1,2-additions or aldol reactions [6]. Previously, many syntheses of optically active a-hydroxy aldehydes were commonly described involving transformation of chiral precursors, enzymatic methods or the use of diastereoselective reactions with chiral starting materials. Asymmetric syntheses starting with achiral substrates were also successfully We already briefly reported shortly in two communications on a new enantioselective synthesis of protected ahydroxy and the diastereo-and enantioselective synthesis of 1,2-amino alcohols[*] employing the hydrazone Aldehydes can be substituted in a-position with high enantioselectivity by electrophilic alkylation of the corresponding deprotonated hydrazone or aminated by nucleophilic 1,2-addition to the hydrazone CN double bond to give optically active amines. Our retrosynthetic analysis of the vicinal amino alcohol structure A led to the 1,2-amino alcohol synthon D with vicinal donor (d) and acceptor (a) reactivities and the corresponding electrophilic (El) and nucleophilic (Nu) reagents. New synthetic equivalents are the pro...
