Rh(iii)-Catalyzed C-H allylation/annulative Markovnikov addition with 5-methylene-1,3-dioxan-2-one: formation of isoquinolinones containing a C3 quaternary centre

The Rh(iii)-catalyzed synthesis of isoquinolinones containing a C3 quaternary centre via a tandem C-H allylation/annulative Markovinkov addition reaction has been achieved. This method employing a single Rh(iii) complex as the catalyst tolerated various functional groups, and was applicable to late-stage diversification of N-methoxyamides derived from steroids and adapalene. By applying the protocol as the key step, US28 inverse agonist analogs were conveniently synthesized.

Automated summary

The Rh(III)-catalyzed synthesis method has been achieved for preparing isoquinolinones containing a C3 quaternary center, which is applicable to late-stage diversification of N-methoxyamides derived from steroids and adapalene. This approach serves as a key step for conveniently synthesizing US28 inverse agonist analogs.