Enantioselective aldehyde alpha-nitroalkylation via oxidative organocatalysis.
The first enantioselective organocatalytic alpha-nitroalkylation of aldehydes has been accomplished. The aforementioned process involves the oxidative coupling of an enamine intermediate, generated transiently via condensation of an amine catalyst with an aldehyde, with a silyl nitronate to produce a beta-nitroaldehyde. Two methods, one that furnishes the syn beta-nitroaldehyde and a second that provides access to the anti isomer, have been developed. Data are presented to support a hypothesis that explains this phenomenon in terms of a silyl group-controlled change in mechanism. Finally, a three-step procedure for the synthesis of both syn- and anti-alpha,beta-disubstituted beta-amino acids is presented.
Wilson
Jonathan E
JE
Merck Center for Catalysis, Princeton University, Princeton, New Jersey 08544, USA.
Casarez
Anthony D
AD
MacMillan
David W C
DW
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry*; D000478:Alkylation; D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000447:Aldehydes; D000588:Amines; D000596:Amino Acids