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

α-alkylation - aldehydes - allylation

Significance

<P>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.</P>

Comment

<P>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.</P>