Asymmetric Darzens Reaction of Isatins with Diazoacetamides Catalyzed by Chiral BINOL-Titanium Complex.

An efficient catalytic asymmetric Darzens reaction of N-protected isatins with diazoacetamides using a chiral BINOL/Ti(OiPr)4 complex as the catalyst has been developed. This reaction is a straightforward method for the synthesis of spiro-epoxyoxindoles in 40-95% yields, up to >20:1 dr and up to >99% ee. A gram-scale reaction was also achieved in 95% yield with excellent stereoselectivity and enantioselectivity (>20:1 dr, >99% ee).