We report herein a gold and palladium sequential catalysis system to access furan-fused nine-membered heterocycles in high efficiency and enantioselectivity. In this one-pot procedure, easily accessible enynamides undergo cyclization to generate azadienes in situ that participate in enantioselective formal [5+4] cycloaddition with vinyl ethylene carbonates. Conformation-controlled highly diastereoselective derivatizations of these medium-sized rings, coupled with oxidative furan cleavage, have enabled the access to diverse densely-functionalized nine-membered lactams.Medium-sized heterocycles (8 to 11-membered rings) are important structural motifs in various bioactive natural products. [1] The synthesis of these medium-sized rings, however, still remains a great challenge for catalytic method development. Out of the different synthetic strategies developed for medium-sized ring formation, intramolecular cyclization or ring expansion is most explored. [2,3] As an alternative and synthetically flexible approach, intermolecular dipolar cycloaddition provides a significant advantage of directly coupling two building blocks (serving as dipoles and dipolarophiles) to produce medium-sized heterocycles. [4] However, success along these lines remains limited, with cycloaddition of only a few classes of 1,4-dipolarophiles reported in the literature. Our group has introduced a dihydrobenzofuran-derived azadiene [5] to realize highly stereoselective Pd-catalyzed cycloadditions for the preparation of nine-or ten-membered benzofuran/indole-fused heterocycles. [5b-d] The same substrate was also used by the Lu group to achieve phosphine-catalyzed enantioselective eight-membered heterocycle synthesis. [6] The Shibata group has introduced CF 3 -substituted benzooxazinones for Pd-catalyzed decarboxylative cycloaddition to access benzo-fused nine-or twelve-membered heterocycles. [7] The formal [5+4] cycloaddition using ortho-quinone methides to access enantioenriched benzo-fused nine-membered rings have also been reported by the Fan group and the Guo group. [8] Despite these advances, it is important to note that due to the special Scheme 1. Diverse nine-membered heterocycles prepared from in situ generated azadienes.
An efficient tandem catalysis method is achieved for the direct conversion of alcohol‐containing alkynyl anilines to valuable chiral 2,3‐fused tricyclic indoles. This method relies on a tandem indolization followed by enantioconvergent substitution of alcohols via borrowing hydrogen to construct two rings in one step, enabled by relay and cooperative catalysis of a chiral iridium complex with a chiral phosphoric acid. Highly diastereoselective transformations of the tricyclic indole products also provide efficient access to a diverse array of complex polycyclic indoline compounds.
We report herein a gold and palladium sequential catalysis system to access furan-fused nine-membered heterocycles in high efficiency and enantioselectivity. In this one-pot procedure, easily accessible enynamides undergo cyclization to generate azadienes in situ that participate in enantioselective formal [5+4] cycloaddition with vinyl ethylene carbonates. Conformation-controlled highly diastereoselective derivatizations of these medium-sized rings, coupled with oxidative furan cleavage, have enabled the access to diverse densely-functionalized nine-membered lactams.Medium-sized heterocycles (8 to 11-membered rings) are important structural motifs in various bioactive natural products. [1] The synthesis of these medium-sized rings, however, still remains a great challenge for catalytic method development. Out of the different synthetic strategies developed for medium-sized ring formation, intramolecular cyclization or ring expansion is most explored. [2,3] As an alternative and synthetically flexible approach, intermolecular dipolar cycloaddition provides a significant advantage of directly coupling two building blocks (serving as dipoles and dipolarophiles) to produce medium-sized heterocycles. [4] However, success along these lines remains limited, with cycloaddition of only a few classes of 1,4-dipolarophiles reported in the literature. Our group has introduced a dihydrobenzofuran-derived azadiene [5] to realize highly stereoselective Pd-catalyzed cycloadditions for the preparation of nine-or ten-membered benzofuran/indole-fused heterocycles. [5b-d] The same substrate was also used by the Lu group to achieve phosphine-catalyzed enantioselective eight-membered heterocycle synthesis. [6] The Shibata group has introduced CF 3 -substituted benzooxazinones for Pd-catalyzed decarboxylative cycloaddition to access benzo-fused nine-or twelve-membered heterocycles. [7] The formal [5+4] cycloaddition using ortho-quinone methides to access enantioenriched benzo-fused nine-membered rings have also been reported by the Fan group and the Guo group. [8] Despite these advances, it is important to note that due to the special Scheme 1. Diverse nine-membered heterocycles prepared from in situ generated azadienes.
An efficient tandem catalysis method is achieved for the direct conversion of alcohol‐containing alkynyl anilines to valuable chiral 2,3‐fused tricyclic indoles. This method relies on a tandem indolization followed by enantioconvergent substitution of alcohols via borrowing hydrogen to construct two rings in one step, enabled by relay and cooperative catalysis of a chiral iridium complex with a chiral phosphoric acid. Highly diastereoselective transformations of the tricyclic indole products also provide efficient access to a diverse array of complex polycyclic indoline compounds.
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