Asymmetric formal sp2-hydrocarbonations of dienes and alkynes via palladium hydride catalysis

Abstract

Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ3 substitution have emerged as a reliable method to construct stereogenic centers, and mainly rely on the use of heteroatom-based or carbon nucleophiles bearing acidic C-H bonds. In comparison, sp2 carbon nucleophiles are generally not under consideration because of enormous challenges in cleaving corresponding inert sp2 C-H bonds. Here, we report a protocol to achieve asymmetric formal sp2 hydrocarbonations, including hydroalkenylation, hydroallenylation and hydroketenimination of both 1,3-dienes and alkynes via hydroalkylation and Wittig reaction cascade. A series of unachievable motifs via hydrofunctionalizations, such as di-, tri- and tetra-substituted alkenes, di-, tri- and tetra-substituted allenes, and tri-substituted ketenimines in allyl skeletons are all facilely constructed in high regio-, diastereo- and enantioselectivities with this cascade design. Stereodivergent synthesis of all four stereoisomers of 1,4-diene bearing a stereocenter and Z/E-controllable olefin unit highlights the power of present protocol. An interesting mechanistic feature is revealed that alkyne actually undergoes hydrocarbonation via the formation of conjugated diene intermediate, different from conventional viewpoint that the hydrofunctionalization of alkynes only involves allene species.

Palladium-Catalyzed Asymmetric O-1,5-Addition with Oximes via Hydroximation of Unsaturated Esters

“…Palladium-catalyzed asymmetric hydrofunctionalizations of unsaturated hydrocarbons have gradually emerged as a powerful route to generate stereocenters . This 100% atom economy process can introduce different nucleophiles to the unsaturated bonds in high stereocontrol. , We thus envisioned that the application of asymmetric hydrofunctionalizations to electron-deficient conjugated diene substrates might provide a convenient route for the absence of a 1,5-conjugate addition reaction. Recently, this strategy was demonstrated feasible but limited to the use of carbon nucleophiles. , Other valuable stereocenters through the adoption of heteroatom nucleophiles are undeveloped.…”