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

• Published in: Journal of organic chemistry Vol. 67; no. 8; pp. 2424 - 2428
• Main Authors: Agami, Claude, Comesse, Sébastien, Kadouri-Puchot, Catherine
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.04.2002; Amer Chemical Soc
• Subjects: Chemical Sciences; Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ENANTIOMERICALLY PURE; TETRAHYDROPYRIDINES; ASYMMETRIC-SYNTHESIS; ORGANOMETALLIC REAGENTS; SILICON; STEREOCHEMISTRY; ALPHA; IMINIUM ION; REGIOSELECTIVITY; VINYLSILANES; Aminoalcohol; Nitrogen heterocycle; Iminium compounds; Lactone; Organic silane; Glyoxal; Stereoselectivity; Reactivity; Cyclization; Pipecolic acid derivatives; Asymmetric synthesis; Vinylic compound; Carbocation; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo010780+

New β-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 β-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.