Enantioselective organocatalytic aminomethylation of aldehydes: a role for ionic interactions and efficient access to beta2-amino acids.
Organocatalytic Mannich addition of aldehydes to a formaldehyde-derived iminium species catalyzed by proline-derived chiral pyrrolidines provides beta-amino aldehydes with >/=90% ee. Mechanistic analysis of the proline-catalyzed reactions suggests that non-hydrogen-bonded ionic interactions at the Mannich reaction transition state can influence stereochemical outcome. The beta-amino aldehydes from our process bear a substituent adjacent to the carbonyl and can be efficiently converted to protected beta2-amino acids, which are important building blocks for beta-peptide foldamers that display useful biological activities.
Chi
Yonggui
Y
Department of Chemistry, University of Wisconsin, Madison, WI 53706, USA.
Gellman
Samuel H
SH
D000447:Aldehydes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D008745:Methylation; D011392:Proline / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D055672:Static Electricity; D013237:Stereoisomerism
D000447:Aldehydes; D000588:Amines; D000596:Amino Acids; D011759:Pyrrolidines; D011392:Proline