The Intriguing Reactivity of Functionalized β-Amino Alcohols with Glyoxal: Application to a New Expedient Enantioselective Synthesis of <i>trans</i>-6-Alkylpipecolic Acids

Abstract

New beta-amino alcohols possessing a vinylsilane moiety were reacted with glyoxal to produce lactones that were transformed in three steps in enantiopure pipecolic acid derivatives. The key step was a totally diastereoselective ene-iminium cyclization, whose mechanism can be viewed as a direct cyclization of the vinylsilane moiety onto the iminium ion. The reactivity of two beta-amino alcohols having an allylsilane terminator was also examined. Their difference of reactivity toward glyoxal can be ascribed to the intervention of a carbocation, which presents a behavior that differs according to the position of the trimethylsilyl group.