Asymmetric and switchable divergent multicomponent reactions involving distinct alkynes via palladium catalysis

Abstract

Asymmetric multicomponent reactions represent an efficient and economic strategy for the construction of complicated structures, and those involving two different alkynes have been rarely explored, probably due to the challenges in sequence control and chemo-, regio-, and stereoselectivity. Here, we disclosed an asymmetric multicomponent cascade vinylogous addition/Sonogashira reaction between 1,3-enynes, N -sulfonylimines, and terminal alkynes catalyzed by Pd(0), which consecutively served as a π-Lewis base catalyst and a traditional coupling catalyst. High selectivity has been achieved; moreover, the cascade reaction with a switchable hydroamination process was realized in a one-pot or stepwise manner by slightly tuning the catalytic conditions, thus furnishing enantioenriched N -heterocycles with an exocyclic double bond in either E or Z configuration stereodivergently. This work provided rapid access to a full set of stereoisomers possessing a stereogenic center and a trisubstituted double bond, and it could arouse more interest in palladium catalysis and asymmetric multicomponent reaction. • An asymmetric palladium-catalyzed reaction involving two alkynes is developed • Switchable stereodivergent synthesis of enantioenriched N -heterocycles is realized • Wide functional groups are tolerated With the advantages of simplicity, efficiency, and atom economy, the asymmetric multicomponent reaction provides easy access to structurally diverse products from independently tunable starting materials. We developed an asymmetric multicomponent process between 1,3-enynes, N -sulfonylimines, and terminal alkynes via π-Lewis base catalysis of Pd(0), which showed a broad substrate scope and was even compatible with the late-stage modification of acetylene-embedding drugs. Moreover, a domino or a sequential hydroamination reaction led to a full set of stereoisomers of N -heterocycles with an exocyclic double bond and a stereogenic center by simply tuning the catalytic conditions. The cascade reaction involving different alkynes—which proceeded in a strictly ordered fashion to furnish densely functionalized products with stereodiversity in high chemo-, regio-, and stereoselectivity—might have more applications in synthetic chemistry. A Pd-catalyzed asymmetric multicomponent reaction between 1,3-enynes, N -sulfonylimines, and terminal alkynes is reported, proceeding in a cascade vinylogous addition and Sonogashira coupling sequence with high chemo-, regio-, and stereoselectivity. A tandem hydroamination process to access N -heterocycles with a switchable Z - or E -exocyclic double bond can be further realized by simply tuning the catalytic conditions.