Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes

Journal of the American Chemical Society
Barry M TrostJames J Cregg

Abstract

Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1 H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.

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Citations

Dec 9, 2020·Chemistry : a European Journal·Minghe SunChangkun Li
Jun 1, 2021·ACS Omega·Tushar M KhopadeRajesh Viswanathan
Aug 3, 2021·Tetrahedron Letters·Bhaskar D Joshi, John D Chisholm
Nov 6, 2018·The Journal of Organic Chemistry·Xianfu ShenHongbin Zhang
May 30, 2020·Chemical Reviews·Vincent PirenneJerome Waser
Sep 22, 2018·Journal of the American Chemical Society·Santanu Panda, Joseph M Ready
Nov 20, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Sourav KunduAlakesh Bisai

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