Rhodium-Catalyzed Highly Regio- and Enantioselective Reductive Cyclization of Alkyne-Tethered Cyclohexadienones

Rhodium-catalyzed
asymmetric hydrogenation of alkyne-tethered cyclohexadienones
enables highly regio- and enantioselective reductive cyclization to
afford cis-hydrobenzofurans and cis-hydroindoles in high yields. Desymmetrization of 1,3-diyne-tethered
cyclohexadienones was also explored, wherein the intramolecular coordination
of a Rh complex with the cyclohexadienone ring induces exclusive regioselectivity.
Mechanistic studies including hydrogen–deuterium crossover
experiments suggested that hydrogen activation is the rate-determining
step for tandem reductive cyclization. Moreover, this highly practical
and atom-economical transformation has tolerance to many functional
groups with a broad range of substrate scope, allowing further transformations
to expand the structural complexity of the bicyclic scaffolds.

铑催化（Rhodium-catalyzed）炔基连接环己二烯酮（alkyne-tethered cyclohexadienones）的不对称氢化（asymmetric hydrogenation）反应，可实现高区域选择性与对映选择性的还原环化（reductive cyclization），以优异收率得到顺式氢化苯并呋喃（cis-hydrobenzofurans）和顺式氢化吲哚（cis-hydroindoles）。研究同时对1,3-二炔基连接环己二烯酮（1,3-diyne-tethered cyclohexadienones）的去对称化（desymmetrization）过程进行了探索，其中铑配合物（Rh complex）与环己二烯酮环的分子内配位（intramolecular coordination）可诱导专一的区域选择性。包括氢氘交换实验（hydrogen–deuterium crossover experiments）在内的机理研究表明，氢活化是串联还原环化（tandem reductive cyclization）反应的决速步（rate-determining step）。此外，该兼具高实用性与原子经济性（atom-economical）的转化可耐受多种官能团（functional groups），底物范围（substrate scope）广泛，还可通过后续衍生反应进一步丰富双环骨架（bicyclic scaffolds）的结构复杂度。