Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ-Carbolines
Dr. Sergiy V. Chepyshev
Department of Chemistry, Drexel University, 32 South 32nd St., Philadelphia, PA, 19104 USA
Search for more papers by this authorProf. J. Armando Lujan-Montelongo
Departmento de Química, Centro de Investigación y de Estudios Avanzados (Cinvestav), Av. Instituto Politécnico Nacional 2508, Ciudad de México, 07360 México
Search for more papers by this authorAllen Chao
Department of Chemistry, Drexel University, 32 South 32nd St., Philadelphia, PA, 19104 USA
Search for more papers by this authorCorresponding Author
Prof. Fraser F. Fleming
Department of Chemistry, Drexel University, 32 South 32nd St., Philadelphia, PA, 19104 USA
Search for more papers by this authorDr. Sergiy V. Chepyshev
Department of Chemistry, Drexel University, 32 South 32nd St., Philadelphia, PA, 19104 USA
Search for more papers by this authorProf. J. Armando Lujan-Montelongo
Departmento de Química, Centro de Investigación y de Estudios Avanzados (Cinvestav), Av. Instituto Politécnico Nacional 2508, Ciudad de México, 07360 México
Search for more papers by this authorAllen Chao
Department of Chemistry, Drexel University, 32 South 32nd St., Philadelphia, PA, 19104 USA
Search for more papers by this authorCorresponding Author
Prof. Fraser F. Fleming
Department of Chemistry, Drexel University, 32 South 32nd St., Philadelphia, PA, 19104 USA
Search for more papers by this authorAbstract
Isocyanides are exceptional building blocks, the wide deployment of which in multicomponent and metal-insertion reactions belies their limited availability. The first conjugate addition/alkylation to alkenyl isocyanides is described, which addresses this deficiency. An array of organolithiums, magnesiates, enolates, and metalated nitriles add conjugately to β- and β,β-disubstituted arylsulfonyl alkenyl isocyanides to rapidly assemble diverse isocyanide scaffolds. The intermediate metalated isocyanides are efficiently trapped with electrophiles to generate substituted isocyanides incorporating contiguous tri- and tetra-substituted centers. The substituted isocyanides are ideally functionalized for elaboration into synthetic targets as illustrated by the three-step synthesis of γ-carboline N-methyl ingenine B.
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