Enantioselective Synthesis of α-Tertiary Hydroxyaldehydes by Palladium-Catalyzed Asymmetric Allylic Alkylation of Enolates

摘要

Chiral α-tertiary hydroxyaldehydes are important functionalized intermedi-ates for the synthesis of natural products. However, reports regarding the useof catalysts for the enantioselective synthesis of a-hydroxyaldehydes fromprochiral precursors have always been lacking. In this study, the authorsused a palladium complex with a chiral ligand as catalyst for the conversionof enol carbonates to α-tertiary hydroxyaldehydes in high regio- and enanti-oselectivity and excellent yields. Capitalizing on previous studies done bythe group on competitive reactions between enolates with labile alkoxygroups producing either a ketone or aldehyde (Fig. 1), the authors exploredthe effects on the enantioselectivity and regioselectivity of the products bythe use of different nucleophiles, R, allylic electrophiles, and various pro-tecting groups for RI. Results have shown that the use of the palladium-ligand complex favored the formation of a-tertiary hydroxyaldehyde overthe ketone (Table 1). Moreover, the same conditions can tolerate varioushydroxy protecting groups for RI, a wide range of aryl, alkenyl, or alkynylgroups, R, and electrophiles of varying ring size. Product yields and enantio-meric excess were generally high. One of the products formed from thisscheme was used as an intermediate for the synthesis of (S)-oxybutynin.