Combining NHC-Cu and Bronsted base catalysis: enantioselective allylic substitution/conjugate additions with alkynylaluminum reagents and stereospecific isomerization of the products to trisubstituted allenes.

Among different types of unsaturated carbon-carbon bonds, allenes carry significant but relatively unexplored potential in chemical synthesis.[1] Research in more recent years has been focused on development of catalytic enantioselective protocols that generate allenes[1] or on providing access to molecules that contain them.[2] Various procedures have been introduced for site-, chemo- and/or stereoselective allene functionalization.[3] Nonetheless, methods of preparation have been largely centered on disubstituted variants;[1] protocols that furnish the trisubstituted allenes, especially those that are catalytic, are less common and typically involve nucleophilic SN2′ additions to enantiomerically enriched alkynyl entities.[4] Among alternative approaches, strategies that deliver trisubstituted allenes through catalytic isomerization of alkyne-containing substrates[5] pose an attractive but somewhat uncharted pathway.[6] We thus envisioned the plan outlined in Scheme 1, involving the feasibility of catalytic and stereospecific isomerization of an enantiomerically enriched alkyne.[7] Bringing such a goal to fruition, however, required a stereoselective catalytic process to effect the desired 1,3-proton shift as well as an efficient, site- and enantioselective method for synthesis of the requisite substrates. Indeed, catalytic enantioselective allylic substitution (EAS) reactions[8] with alkynyl nucleophiles are rare;[9] related catalytic enantioselective processes that generate tertiary stereogenic carbon centers are unknown.[10] Herein, we describe the realization of the plan illustrated in Scheme 1 to address the abovementioned shortcomings.