Stereoselective synthesis of trisubstituted (E,E)-1,3-dienes by the site-selective reductive cross-coupling of internal alkynes with terminal alkynes: a fragment coupling reaction for natural product synthesis

A highly selective convergent coupling reaction between alkynes for the synthesis of stereodefined trisubstituted (E,E)-1,3-dienes-structural motifs commonly found embedded in the skeletons of bioactive polyketide-derived natural products is described. The preparation of complex 1,3-dienes relevant for the synthesis of polyketide-derived natural products of varying stereochemistry with typically [greater than equal to] 20:1 selectivity defined the important role of an alkoxide directing group located [delta] to preformed titanacyclopropenes is also reported.