A Catalytic Asymmetric Ring-Expansion Reaction of I satins and α-Alkyl-α-Diazoesters: Highly Efficient Synthesis of Functionalized 2-Quinolone Derivatives

摘要

The ring-expansion reaction of cyclic ketones and diazo compounds is a classical way to expand the ring size of cyclic carbonyl compounds by one-carbon unit. The ring expansion of isatin and other ketones with diazomethane was reported early in the last century. Since then, a number of advances have been made, such as the development of variants that use α-diazoesters, which are more stable and less reactive than α-diazoalkanes. However, the development of catalytic asymmetric variants seems particularly difficult. Innovative approaches have recently been reported by Kingsbury and co-workers and by Maruoka and co-workers. However, the catalytic reactions developed by these research groups involved the ring expansion of symmetric aliphatic cyclic ketones through 1,2-alkyl migration. Extremely low reaction temperatures and high catalyst loadings were required, especially when α-alkyl-d-diazoesters were used to incorporate all-carbon quaternary centers. To the best of our knowledge, asymmetric ring expansion of prochiral cyclic carbonyl compounds, which usually suffer from complicated regiochemical problems, has not been documented to date. Although isatin was chosen as the substrate in the first example of a ring-expansion reaction with diazomethane, a reaction that was reported in the year 1919, an asymmetric ring expansion of isatins has not been reported. In this reaction multiple products are possible because of competitive 1,2-aryl migration and 1,2-carbonyl migration reaction pathways (Scheme 1). Thus, the development of a suitable catalyst for the ring expansion of unsymmetric substrates with high regio- and enantiocontrol is particularly desirable, albeit challenging. In a continuation of our research with diazo compounds, we report herein a highly enantioselective ring-expansion reaction of isatins and aα-alkyl-α-diazoesters involving 1,2-aryl migration.