β-Functionalization of Carboxylic Anhydrides with N-Heterocyclic Carbenes

Key words

anhydrides - N-heterocyclic carbenes - β-functionalization

Significance

Chi, Yang, and co-workers report the asymmetric β-functionalization of symmetrical aliphatic anhydrides 1. Nucleophilic attack of the N-heterocyclic carbene catalyst to the anhydride generates the NHC-bound ester intermediate, which upon deprotonation forms nucleophile 2. This adds to various electrophiles, such as alkylidene diketones, chalcones, and isatins, in a highly selective manner. Decarboxylation of the β-lactone intermediates 3 yields the final products. For almost all substrates tested, consistently very high enantioselectivities accompanied with good diastereoselectivities were achieved.

Comment

In continuation of the work by the Chi group on the activation of esters with NHC catalysts for the functionalization of the β-position (Nature Chem. 2013, 5, 835), overcoming the limitation of β-aryl substrates is the main objective of the current work. Under the previous reaction conditions, only low yields (8−40%) were obtained. The presented solution for these challenging substrates utilizes anhydride substrates instead, affording the desired products in moderate to very good yields under the optimized conditions.