Linchpin construction of unsymmetrical 1,4-alkynediols

A one-pot preparation of unsymmetrical 1,4-alkynediols such as 2a by the coupling of trimethylsilylacetylene and two different aldehydes or ketones is reported. The dilithiated species 5 is generated by the sequential addition of the first aldehyde or ketone 1b to a solution of lithium trimethylsilylacetylide, followed by the addition of methyllithium, which removes the trimethylsilyl protecting group. Addition of the second aldehyde or ketone then leads to the unsymmetrical 1,4-alkynediol 2a.