Iridium-Catalyzed Enantioselective and Chemodivergent Allenylic Alkylation of Vinyl Azides for the Synthesis of α-Allenylic Amides and Ketones.

The first enantioselective synthesis of α-allenylic amides and ketones through allenylic alkylation of vinyl azides is reported. In these chemodivergent reactions, cooperatively catalyzed by a IrI /(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. Utilizing racemic allenylic alcohols as the alkylating agent, the overall process represents a dynamic kinetic asymmetric transformation (DyKAT), where both the products are formed with the same absolute configuration. 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.

Hydroxy-directed iridium-catalyzed enantioselective formal ß-C(sp2)-H allylic alkylation of α,ß-unsaturated carbonyls.

Hydroxy-directed iridium-catalyzed enantioselective formal ß-C(sp2)-H allylic alkylation of kojic acid and structurally related α,ß-unsaturated carbonyl compounds is developed. This reaction, catalyzed by an Ir(i)/(P,olefin) complex, utilizes the nucleophilic character of α-hydroxy α,ß-unsaturated carbonyls, to introduce an allyl group at its ß-position in a branched-selective manner in good to excellent yield with uniformly high enantioselectivity (up to >99.9 : 0.1 er). To the best of our knowledge, this report represents the first example of the use of kojic acid in a transition metal catalyzed highly enantioselective transformation.

Iridium-Catalyzed Enantioselective α-Allylic Alkylation of Amides Using Vinyl Azide as Amide Enolate Surrogate.

Among the unstabilized enolates used as nucleophiles in iridium-catalyzed asymmetric allylic alkylation reactions, amide enolates are the least explored. Vinyl azides are now employed as amide enolate surrogates in Ir-catalyzed asymmetric allylic alkylation with branched allylic alcohols as the allylic electrophile. Competing reaction pathways are suppressed through the systematic tuning of the steric and electronic properties of vinyl azide to effect the α-allylic alkylation of secondary acetamides with high atom economy, exclusive branched selectivity, and mostly excellent enantioselectivity.