Carreira alkynylations with paraformaldehyde. 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 °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.