Catalytic asymmetric aldol reactions of enolizable carbon pronucleophiles with formaldehyde and ethyl glyoxylate

We herein describe novel catalytic asymmetric aldol reactions of acidic carbon pronucleophiles including beta-keto esters and specific ketones with reactive electrophiles such as formaldehyde and ethyl glyoxylate. In the presence of a catalytic amount of chiral Pd(II)-BINAP complexes, the hydroxymethylation of beta-keto esters with paraformaldehyde or formalin was examined, and the corresponding adducts were obtained in good yields with good to high enantioselectivity (ca. 86% ee). In some cases, the similar Pt(II) complex also worked well to give the products with better enantioselectivity. Furthermore, these complexes were found to promote the aldol reactions of less acidic ketones, and ethyl glyoxylate underwent reaction with 3-coumaranone and beta-tetralone, affording the aldol products with a significant level of enantioselectivity of up to 83 % ee.