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. 2017 Apr 3;56(15):4310-4313.
doi: 10.1002/anie.201612574. Epub 2017 Mar 13.

Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ-Carbolines

Sergiy V Chepyshev  1 , J Armando Lujan-Montelongo  2 , Allen Chao  1 , Fraser F Fleming  1
Affiliations

Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ-Carbolines

Sergiy V Chepyshev et al. Angew Chem Int Ed Engl. .

Abstract

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.

Keywords: conjugate addition; isocyanides; organometallics; synthetic methods; γ-carbolines.

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Figures

Figure 1
Figure 1
Isocyanide representations.
Scheme 1
Scheme 1
Synthesis and addition to sulfonylisocyanide 3a.
Scheme 2
Scheme 2
Conjugate addition-alkylation mechanism.
Scheme 3
Scheme 3
Isocyanide cyclization to γ-carbolines.
Scheme 4
Scheme 4
Synthesis of N-Methyl ingenine B (20).
See this image and copyright information in PMC

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