Iridium-Catalyzed Enantioselective Formal meta-Allenylation of Pyridines
Pankaj Roy1, Pratibha Mahto1, Santanu Mukherjee1
1Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Abstract:
Site-selective functionalization of pyridines is an important yet challenging transformation. Temporary dearomatization of pyridines through redox-neutral cycloaddition has recently emerged as a reliable and attractive strategy for meta-functionalization of pyridines. Despite the amenability of the resulting bench-stable cycloadduct, oxazinopyridine, to a variety of electrophilic and radical-based reagents, its enantioselective functionalization remains unexplored. Herein, we present the first enantioselective meta-functionalization of pyridines through the intermediacy of oxazinopyridines. This highly enantioselective formal meta-allenylation of pyridines is achieved by treating the easily accessible oxazinopyridines with racemic allenylic alcohol under the combination of a catalytic amount of an Ir(I)/(P, olefin) complex and Lewis acidic Sc(OTf)3 followed by acid-mediated rearomatization. With oxazinopyridines derived from unsubstituted or suitably substituted pyridines, iterative 3,5-difunctionalization is possible, which also allows for the stereodivergent synthesis of all four stereoisomers of 3,5-bis-allenylic pyridines.
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