Stereospecific rearrangement of optically active tertiary allylic epoxides to give optically active quaternary aldehydes: Synthesis of α-alkyl amino aldehydes and acids

Article abstract of DOI:10.1021/ja00133a011

2-Methyl-2-vinyl-3-alkyloxiranes, readily obtained from Sharpless-Katsuki asymmetric epoxidation of allylic alcohols, undergo facile 1,2-alkyl migration with inversion of configuration leading to 2-methyl-2-vinylalkanals, thereby establishing an acyclic quaternary carbon in high yield and optical purity. The reaction conditions necessary for rearrangement are generally quite mild, e.g., BF₃·OEt₂ at -78°C for 2 min, 5 M LiClO₄ in refluxing ether, anhydrous Zn(OTf)₂ or ZnCl₂, EtAlCl₂, silica gel, and sonication. As an application of this methodology, and to prove the stereochemical course of the process, the synthesis of (S)-(-)-α-methylphenylalanine [(+)-16a] is described. This methodology also permits access to optically active N-protected amino aldehydes [i.e., (-)-15a and (-)-15b], compounds which are difficult to make by other routes. The key step in each case is the rearrangement of (-)-8a or (-)-8b to give the quaternary aldehydes (+)-9a or (+)-9b in good yield and optical purity.