Decarboxylative oxidation-enabled consecutive C-C bond cleavage

The selective cleavage of inert C(sp3)-C(sp3) bonds and their subsequent functionalization is an important goal in synthetic organic chemistry. Here, the authors developed consecutive C-C bond cleavage from stable trisubstituted acids via photocatalysis and copper catalysis. The selective cleavage of C-C bonds is of fundamental interest because it provides an alternative approach to traditional chemical synthesis, which is focused primarily on building up molecular complexity. However, current C-C cleavage methods provide only limited opportunities. For example, selective C(sp(3))-C(sp(3)) bond cleavage generally relies on the use of transition-metal to open strained ring systems or iminyl and alkoxy radicals to induce beta-fragmentation. Here we show that by merging photoredox catalysis with copper catalysis, we are able to employ alpha-trisubstituted carboxylic acids as substrates and achieve consecutive C-C bond cleavage, resulting in the scission of the inert beta-CH2 group. The key transformation relies on the decarboxylative oxidation process, which could selectively generate in-situ formed alkoxy radicals and trigger consecutive C-C bond cleavage. This complicated yet interesting reaction might help the development of other methods for inert C(sp(3))-C(sp(3)) bond cleavage.