Palladium-Catalyzed Asymmetric Hydroxymethylations

Significance

A novel catalytic asymmetric aldol reaction of acidic carbon pronucleophiles is achieved using chiral Pd(II) and Pt(II) BINAP complexes. These hydroxymethylation reactions are possible with acyclic and cyclic β-keto esters and ketones as pronucleophiles, and highly reactive formaldehyde and ethylglyoxylate as electrophiles. Under the reaction conditions, paraformaldehyde is converted into monomeric formaldehyde, providing hydroxymethylated α-all carbon stereocenters with moderate to good yields and ee values. Direct acetylation of the product with pres­ervation of enantioselectivity is possible by adding acetyl chloride and pyridine to the catalytic reaction, although very large excess of these reagents are required.