Iridium Catalyzed Enantioselective C3 Allenylation of Pyridines

An enantioselective C3-allenylation of pyridines has been developed through the intermediacy of oxazino pyridines. This dearomatization/electrophilic substitution/rearomatization strategy leverages the nucleophilicity of oxazino pyridines, whose enamine/dienamine-like reactivity is combined with iridium-activated allenylic carbocations to achieve a formal C3-allenylation of pyridines. Using racemic allenylic alcohols as the allenylic electrophile, this reaction is catalyzed by an Ir(I)/(P,olefin) complex, and delivers a wide range of C3-allenylic pyridines in moderate to good yields with excellent level of enantioselectivity (up to >99.9:0.1 er). The modularity of this approach allows for not only subsequent electrophilic chlorination but also the deadenylation of pyridines. The latter reaction allows access to all possible stereoisomers of 3,5-diallenylic pyridines with excellent diastereo- and enantioselectivity in a three-step, two-pot process. This is the first example of an enantioselective transformation of oxazino pyridines en route to chiral C3-functionalized pyridines.