The b-amino alcohol and a-hydroxy-b-amino acid moieties are found in a large variety of biologically important compounds and natural products [1] as well as in a growing number of ligands and chiral auxiliaries for asymmetric synthesis. [2] Existing synthetic routes towards enantiopure vicamino alcohols have traditionally relied on derivatization of the chiral pool of amino acids for the most part; however, there is an inherent limitation of accessible targets. [3] Considerable efforts have been made in developing asymmetric routes to b-amino alcohols to circumvent these drawbacks; these can be divided into two strategically different approaches. [4] Most commonly, the amino alcohol functionality is introduced into a pre-existing carbon skeleton, and this can be accomplished by Sharpless aminohydroxylation [5] or by ring opening of epoxides [4,6,7] or aziridines [4,7, 8] with appropriate nucleophiles. More effectively, the amino alcohol moiety can be constructed by concomitant formation of a new carbon-carbon bond and two vicinal stereogenic centers in a single step. This approach has been realized by addition of glycine-derived enolates to aldehydes to yield anti-b-amino alcohols [1b, 9] or by addition of a-alkoxy enolates to aldimines in a Mannich-type reaction. [1a, 10] Although several methods are currently available for the stereo-and enantioselective formation of vic-amino alcohols, there is clearly a demand for simple and efficient entries to this interesting class of substance.
It was envisioned that vic-amino alcohols A could be obtained by hydrolysis of the corresponding oxazolidines B, and that these heterocycles could be prepared from the 1,3dipolar cycloaddition of a carbonyl ylide C to an imine D (Scheme 1). [11] The carbonyl ylide C, in turn, could be prepared from insertion of the carbene derived from E into aldehyde F. Herein, we report the realization of this strategy by detailing the first example of such a three-component protocol for the synthesis of syn-a-hydroxy-b-amino esters and its application to the asymmetric synthesis of the C13 taxol side chain.