Generation of organolithium compounds bearing super silyl ester and their application to Matteson rearrangement.

Abstract

Organolithium compounds are versatile intermediates in organic synthesis. Since they are highly reactive and readily available from organohalides by lithium/halogen exchange, their reaction with various electrophiles is one of the most powerful methods for C-C bond formation.[1] However, their synthetic utility has been restricted due to limited functional group compatibility. For example, organolithium compounds bearing an ester group significantly suffer from self-condensation (Figure 1a). Since direct transformation of ester derivatives provides a concise synthetic route for numerous organic compounds, great efforts have been made to solve this long standing problem. One solution to utilize such an unstable intermediate is the use of a microflow system described by Yoshida et al.[2] They found the microflow reactor allows the direct lithiation of aryl halides bearing an ester group and the subsequent reaction with electrophiles.[2a, b] On the other hand, a wide range of functional groups are compatible with less reactive organometallic reagents such as organozinc[3] and organomagnesium[4] reagents. Knochel et al. reported the Turbo Grignard reagent (iPrMgBr·LiCl) undergoes metal/halogen exchange with aryl halides and the resulting arylmagnesium reagents demonstrate high tolerance toward electrophilic functional groups. Despite the advance of these alternative methods, a general strategy for direct lithiation in a macrobatch reactor that is compatible with the ester functional group has not been accomplished. Toward this end, the utilization of an unaffected ester under highly nucleophilic conditions would be straightforward and advantageous. Even the sterically demanding tert-butyl ester, however, requires extremely low temperature to suppress the self-condensation.[5] Therefore, the development of a robust protecting group for carboxylic acids, which can be easily masked and removed, is desirable.