Organocatalytic cycloaddition of alkynylindoles with azonaphthalenes for atroposelective construction of indole-based
Hui Yang1, Huai-Ri Sun1, Rui-Qing He1
1Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry & Materials Science, National Demonstration Center for Experimental Chemistry Education, Northwest University, Xi'an, 710127, P. R. China.
Abstract:
The axially chiral indole-aryl motifs are present in natural products and biologically active compounds as well as in chiral ligands. Atroposelective indole formation is an efficient method to construct indole-based biaryls. We report herein the result of a chiral phosphoric acid catalyzed asymmetric cycloaddition of 3-alkynylindoles with azonaphthalenes. A class of indole-based biaryls were prepared efficiently with excellent yields and enantioselectivities (up to 98% yield, 99% ee). Control experiment and DFT calculations illustrate a possible mechanism in which the reaction proceeds via a dearomatization of indole to generate an allene-iminium intermediate, followed by an intramolecular aza-Michael addition. This approach provides a convergent synthetic strategy for enantioselective construction of axially chiral heterobiaryl backbones.
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