Carreira Alkynylations with Paraformaldehydee A Mild and Convenient Protocol for the Hydroxymethylation of Complex Base-Sensitive Terminal Acetylenes via Alkynylzinc Triflates

A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 degrees C. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metalation. While N-methylephedrine (NME) is generally the best Zn(OTf)(2)-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.