Organocatalytic Asymmetric 1,6-Additions of β-Ketoesters and Glycine Imine

The first organocatalytic enantioselective 1,6-addition of β-ketoesters and benzophenone imine
to electron-poor δ-unsubstituted dienes using cinchona alkaloids under phase-transfer conditions is
demonstrated. The scope of the reaction for the β-ketoesters is outlined for reactions with different
δ-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 β-ketoesters having different ring sizes, ring
systems and substituents in high yields and enantioselectivities. The potential of this new organocatalytic
1,6-addition for β-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 α-amino acid derivative to highly attractive
optically active pyrrolidines.