Enantioselective Nucleophilic Vinylic Substitution (S_NV) toward 3-Alkenyl-bisoxindoles Facilitated by C6′ Steric Bulk of Cinchona Alkaloid

Abstract

A C6′ bulky substituted quinine-catalyzed SNV reaction between 3-substituted oxindole and (E)-3-(nitromethylene)-oxindole was developed. This enantioselective C­(sp 3)–C­(sp 2) coupling furnished bisoxindole scaffolds featuring a vinyl-substituted all-carbon quaternary stereocenter with high stereoselectivities. In addition, the gram-scale synthesis and synthetic post-transformations were conducted to demonstrate the potential synthetic usefulness.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts

“…Chiral 3,3′-bisindolyl core structures with all-carbon quaternary stereocenters serve as key intermediates for the construction of bisindole alkaloids. Some asymmetric synthetic strategies − had been successfully reported to synthesize chiral 3,3′-bisindolyl derivatives (Scheme b). In 2011, the Trost group exemplified a Pd-catalyzed asymmetric addition of oxindoles to allenes in the presence of an acid cocatalyst to allow the formation of 3-substituted 3-indolyloxindoles with two vicinal stereocenters .…”

“…Catalytic asymmetric transformation of 3-hydroxy-3-indolyloxindoles represents another feasible method. Several groups developed chiral phosphoric acid-catalyzed direct alkylation of 3-hydroxy-3-indolyloxindoles with nucleophilic ketone counterparts for the synthesis of 3-substituted 3-indolyloxindoles. , In addition, asymmetric syntheses of other types of 3,3′-bisindolyl skeletons were also reported using asymmetric 1,4-conjugate addition, , the Friedel–Crafts reaction, the organo-catalyzed nucleophilic substitution reaction, ,, as well as the metal–organic cocatalyzed multicomponent tandem reaction . However, with a view to the synthetic value of enantiomerically enriched 3,3′-bisindoles, the development of useful and versatile methods is still highly demanded.…”