Synthesis of a polymer-bound galactosylamine and its application as an immobilized chiral auxiliary in stereoselective syntheses of piperidine and amino acid derivatives.
A 2,3,4-tri-O-pivaloylated beta-D-galactopyranosyl azide bearing a hydroxy-functionalized spacer unit at the C-6 position of the galactose was synthesized and immobilized on the solid phase by using a polymer-bound chlorosilane. The azide was reduced to the corresponding galactopyranosylamine, which served as a versatile chiral auxiliary in highly diastereoselective Ugi four-component condensation reactions at ambient temperature. Fluoride-induced cleavage from the polymeric support furnished N-glycosylated N-acylated alpha-amino acid amides. The reaction of the immobilized galactosylamine with aldehydes gave rise to the corresponding aldimines, which underwent a domino Mannich-Michael condensation reaction with Danishefsky's diene at ambient temperature to yield 2-substituted 5,6-didehydropiperidin-4-ones on the solid phase. Subsequent cleavage with tetra-n-butylammonium fluoride delivered the N-glycosylated products in high yields, purities, and diastereoselectivities. A chemoselective 1,4-hydride addition to the polymer-bound dehydropiperidinones was achieved in the presence of the bulky oxygenophilic Lewis acid methylaluminum [bis(2,6-di-tert-butyl-4-methylphenoxide)]. The conjugate addition of cyano-modified Gilman reagents to the immobilized dehydropiperidinones furnished 2,6-cis-substituted piperidine derivatives as the major diastereomers that were isolated after cleavage from the support.
Zech
Gernot
G
Institut für Organische Chemie der Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
Kunz
Horst
H
D000596:Amino Acids / Q000138:chemical synthesis*; D002853:Chromatography, Liquid; D002855:Chromatography, Thin Layer; D005688:Galactosamine / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis*; D011108:Polymers; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000596:Amino Acids; D007202:Indicators and Reagents; D010880:Piperidines; D011108:Polymers; D005688:Galactosamine