α-Allylation of Aldehydes via a Conjugate Addition-Elimination Pathway

Key words

α-alkylation - aldehydes - allylation

Significance

A catalytic asymmetric α-alkylation of aldehydes with allylic bromides 3, proceeding via an S_N2′-type conjugate addition-elimination pathway, has been reported. Stoichiometric DMAP and catalytic amounts of secondary amine 1 delivered alkylation products 4 in moderate yields with high enantioselectivity. Using a more complex electrophile 6, product 7 was obtained with excellent enantioselectivity albeit in only 40% yield after three days. In addition to moderate yields, the main drawback of the reported method is the use of three equivalents of the aldehyde.

Comment

The widely pursued catalytic asymmetric α-alkylation of aldehydes has recently been advanced by using secondary amine catalysis via an intramolecular S_N2 pathway, an intermolecular radical pathway, and also via S_N1-type reactions. However, limitations of available methods with respect to suitable electrophiles prompted further research. In the current paper, Palomo and co-workers designed a system that circumvents catalyst alkylation probably by making it reversible. The crucial step of the reaction is based on a conjugate addition (A + B → C) rather than on a direct alkylation. DMAP serves a dual role: activating the electrophile via intermediate B (for example, see: Y.-C. Chen et al. Angew. Chem. Int. Ed. 2009, 48, 5737) and acting as a base to remove the liber­ated acid.