Enantioselective Heck/Tsuji-Trost reaction of flexible vinylic halides with 1,3-dienes.

Zhang, Li-Zhi; Zhang, Pei-Chao; Wang, Qian; Zhou, Min; Zhang, Junliang · Nat Commun · 2025

basic_science · Level V

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Abstract

The enantioselective domino Heck/cross-coupling has emerged as a powerful tool in modern chemical synthesis for decades. Despite significant progress in relative rigid skeleton substrates, the implementation of asymmetric Heck/cross-coupling cascades of highly flexible haloalkene substrates remains a challenging and and long-standing goal. Here we report an efficient asymmetric domino Heck/Tsuji-Trost reaction of highly flexible vinylic halides with 1,3-dienes enabled by palladium catalysis. Specifically, the Heck insertion as stereodetermining step to form ƞ<sup>3</sup> allyl palladium complex and in situ trapping with nucleophiles enable efficient Heck/etherification in a formal (4 + 2) cycloaddition manner. Engineering the Sadphos bearing androgynous non-C<sub>2</sub>-symmetric chiral sulfinamide phosphine ligands are vital component in achieving excellent catalytic reactivity and enantioselectivity. This strategy offers a general, modular and divergent platform for rapidly upgrading feedstock flexible vinylic halides and dienes to various value-added molecules and is expected to inspire the development of other challenging enantioselective domino Heck/cross-couplings.