Organocatalytic asymmetric 1,6-additions of beta-ketoesters and glycine imine.
The first organocatalytic enantioselective 1,6-addition of beta-ketoesters and benzophenone imine to electron-poor delta-unsubstituted dienes using cinchona alkaloids under phase-transfer conditions is demonstrated. The scope of the reaction for the beta-ketoesters is outlined for reactions with different delta-unsubstituted dienes having ketones, esters, and sulfones as electron-withdrawing substituents giving the corresponding optically active products in good yields and enantioselectivities in the range of 90-99% ee. The 1,6-addition also proceeds with a number of cyclic beta-ketoesters having different ring sizes, ring systems and substituents in high yields and enantioselectivities. The potential of this new organocatalytic 1,6-addition for beta-ketoesters is demonstrated by a two-step synthesis of the bicyclo[3.2.1]octan-8-one structure, a bicyclic bridged skeleton occurring in a variety of natural compounds. Benzophenone imines also undergo the organocatalytic asymmetric 1,6-addition to the activated dienes in high yields and with enantioselectivities from 92% to 98% ee, except in one case. The synthetic utility of this asymmetric reaction is demonstrated by the two-step transformation of the allylated alpha-amino acid derivative to highly attractive optically active pyrrolidines.
Bernardi
Luca
L
Danish National Research Foundation, Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
López-Cantarero
Jesús
J
Niess
Barbara
B
Jørgensen
Karl Anker
KA
D000146:Acids, Carbocyclic / Q000138:chemical synthesis; D001577:Benzophenones / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D004952:Esters / Q000138:chemical synthesis; D005998:Glycine / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D007651:Keto Acids / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry
D000146:Acids, Carbocyclic; D001577:Benzophenones; D004952:Esters; D007097:Imines; D007651:Keto Acids; D011759:Pyrrolidines; D014753:Vinyl Compounds; D005998:Glycine