Ag2O/squaramide cocatalyzed asymmetric interrupted Barton-Zard reaction of 8-nitroimidazo[1,2-a]pyridines.

Imidazo[1,2-a]pyridines are present in numerous biologically active compounds as the core structural motif. Herein, we report an asymmetric interrupted Barton-Zard reaction of electron-deficient imidazo[1,2-a]pyridines with α-substituted isocyanoacetates. The reaction enables the dearomatization of 8-nitroimidazo[1,2-a]pyridines and hence offers straightforward access to an array of optically active highly functionalized imidazo[1,2-a]pyridine derivatives that possess three contiguous stereogenic centers in good yields (up to 98%) with high stereoselectivities (>19:1 dr, >99% ee). It is worth noting that the catalytic system consisting of a chiral squaramide and silver oxide displays remarkable reactivity and stereoselectivity, and a gram-scale reaction is compatible with the catalyst loading of 0.5 mol%. In addition, the synthetic potential of this method was showcased by versatile transformations of the product.