Enantioselective organo-cascade catalysis.
A new strategy for organocatalysis based on the biochemical blueprints of biosynthesis has enabled a new laboratory approach to cascade catalysis. Imidazolidinone-based catalytic cycles, involving iminium and enamine activation, have been successfully combined to allow a large diversity of nucleophiles (furans, thiophenes, indoles, butenolides, hydride sources, tertiary amino lactone equivalents) and electrophiles (fluorinating and chlorinating reagents) to undergo sequential addition with a wide array of alpha,beta-unsaturated aldehydes. These new cascade catalysis protocols allow the invention of enantioselective transformations that were previously unknown, including the asymmetric catalytic addition of the elements of HF across a trisubstituted olefin. Importantly, these domino catalysis protocols can be mediated by a single imidazolidinone catalyst or using cycle-specific amine catalysts. In the latter case, cascade catalysis pathways can be readily modulated to provide a required diastereo- and enantioselective outcome via the judicious selection of the enantiomeric series of the amine catalysts. A central benefit of combining multiple asymmetric organocatalytic events into one sequence is the intrinsic requirement for enantioenrichment in the second induction cycle, as demonstrated by the enantioselectivities obtained throughout this study (>/=99% ee in all cases).
Huang
Yong
Y
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Walji
Abbas M
AM
Larsen
Catharine H
CH
MacMillan
David W C
DW
D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis*; D002384:Catalysis; D007093:Imidazoles / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D008956:Models, Chemical; D009930:Organic Chemicals / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000447:Aldehydes; D000588:Amines; D001688:Biological Products; D007093:Imidazoles; D007097:Imines; D009930:Organic Chemicals