Catalytic Asymmetric Diarylation of Internal Acyclic Styrenes and Enamides

Abstract

Enantioselective transformations of olefins are among the most important strategies for the asymmetric synthesis of organic compounds. Chemo-, diastereo-, and stereoselective control of reactions with internal acyclic alkenes for the construction of functionalized acyclic alkanes still remain a persistent challenge. Here, we report a palladium-catalyzed asymmetric regiodivergent Heck-type diarylation of internal acyclic alkenes. The 1,2-diarylation of two accessible acyclic alkenes, cinnamyl carbamates and enamides with diazonium salts and aromatic boronic acids, furnishes products containing vicinal stereogenic centers via the stereospecific formation of carbonyl coordination-assisted transient palladacycles. Moreover, the asymmetric migratory diarylation of enamides enables the formation of incontiguous stereocenters by an interrupted diastereoselective 1,3-chain-walking process. This protocol streamlines access to highly functionalized multisubstituted enantioenriched carbamates and amine derivatives which are embedded in the key biologically active motifs.

Recent Advances in Transition-Metal-Catalyzed Asymmetric Functionalization of Enamides

“…Chen and co-workers reported a Pd-catalyzed multicomponent regiodivergent Heck-type diarylation of internal enamides with aryl boronic acids and aryl diazonium salts (Scheme 24). 47 A wide range of coupling components and internal enamides bearing different functional groups could be coupled to give various chiral 1,2,2-triaryl ethylamine and 1,3,3-triaryl propylamine derivatives with high reigo-, diastero-and enantioselectivity. Intuitively, the choice of aryl on enamides was crucial to stabilized benzylic palladium intermediate, allowing for facile 1,2-diarylation.…”

Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes

“…Notwithstanding these important progresses, they are limited to the generation of a single stereocenter. The metal-catalyzed enantioselective synthesis of γ-branched amines containing vicinal stereocenters in an acyclic system has not been disclosed thus far . The absence of such a catalytic method is a consequence of combined challenges associated with the generation of a remote stereocenter and the simultaneous control of the diastereoselectivity.…”

Palladium(ii)-catalyzed enantioselective intermolecular oxidative diarylation of internal enamides

“…15 Very recently, we disclosed Pd(0)-catalyzed three-component cross-coupling with the use of aryl diazonium salts as electrophiles and aryl boronic acids as nucleophiles to regiodivergently achieve the enantioselective 1,2-diarylation and 1,3-diarylation of enamides. 16 As part of our continuous interest in asymmetric difunctionalization of alkenes, 9f, [15][16][17] we envision that asymmetric oxidative Pd(II)/Pd(0) catalysis would be applicable to the asymmetric diarylation of alkenes. In this communication, we present our latest investigations of the first example of Pd(II)-catalyzed asymmetric oxidative interrupted Heck-Suzuki reaction of internal enamides to forge two C-C bonds with excellent diastereo-and enantioselectivity.…”