Modular synthesis of unsymmetrical all-carbon tetrasubstituted alkenes via Pd-catalyzed multi-component coupling.

Abstract

Tetrasubstituted alkenes constitute privileged architectures in material science, biomedicine, and chemistry. However, achieving their stereocontrolled synthesis-especially for molecules with four distinct substituents-remains a formidable challenge, as conventional methods lack the necessary modularity and stereoselectivity. Herein, we report a palladium-catalyzed three-component cascade reaction that directly couples alkynyl tetracoordinate boron compounds with two different aryl halides in a single vessel. The reaction proceeds through initial coupling with one aryl halide to form an alkenylboron intermediate, followed by a second Suzuki-type coupling with the other aryl halide. This strategy effectively addresses long-standing challenges of chemoselectivity and byproduct formation in the synthesis of tetrasubstituted alkenes. It enables the modular assembly of unsymmetrical tetrasubstituted alkenes with precise control over chemo-, regio-, and stereoselectivity. Notably, this method provides access even to the most challenging targets bearing four distinct substituents in a stereodefined manner. The reaction proceeds under mild conditions, exhibits exceptional functional group tolerance, and accommodates a broad substrate scope (>100 examples). Significantly, several derivatives exhibit aggregation-induced emission (AIE) with a distinct bathochromic shift (red-shift) in the solid state, underscoring the potential of this unique alkene architecture for developing solid-state red-emitters. Furthermore, we demonstrate the concise synthesis of the pharmaceutical agents Toremifene and Tamoxifen using this method. This work establishes a versatile and practical platform for accessing these coveted architectures, with broad implications for synthetic chemistry and materials science.