Ir-Catalyzed Chemodivergent Allenylic Alkylation of Vinyl Az-ides: Highly Enantioselective Synthesis of α-Allenylic Amides and Ketones

Enantioselective allenylic alkylation reactions of unstabilized enolates have never been reported. We now present a unified fragment-coupling strategy for the first enantioselective synthesis of α-allenylic amides and ketones through allenyl-ic alkylation of vinyl azides. In these chemodivergent reactions, cooperatively catalyzed by Ir(I)/(phosphoramidite,olefin) complex and Sc(OTf)3, vinyl azides act as the surrogate for both amide enolates and ketone enolates. The desiccant (molecular sieves) plays a crucial role in controlling the chemodivergency of this enantioconvergent and regioselective reaction: Under otherwise identical reaction conditions, the presence of the desiccant led to α-allenylic amides while its absence resulted in α-allenylic ketones from the same substrate combinations. Utilizing race-mic allenylic alcohols as the alkylating agent, the overall process represents a dynamic kinetic asymmetric transformation (DyKAT), where both α-allenylic amides and ketones are formed with the same absolute configuration generally with outstanding enantioselectivity. To the best of our knowledge, this is the first example of the use of vinyl azide as the ketone enolate surrogate in an enantioselective transformation.

Enantioconvergent alkylation of ketones with racemic secondary alcohols via hydrogen borrowing catalysis

An enantioconvergent hydrogen borrowing strategy enables the catalytic asymmetric alkylation of ketone enolates with unactivated, racemic secondary alcohols.

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

Due to their closely matched reactivity, the coupling of two dissimilar ketone enolates to form a 1,4-diketone remains a challenge in organic synthesis. We herein report that umpolung of a ketone trimethylsilyl enol ether (1 equiv) to form a discrete enolonium species, followed by addition of as little as 1.2–1.4 equivalents of a second trimethylsilyl enol ether, provides an attractive solution to this problem. A wide array of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition.