Chromium-catalyzed para-selective formation of quaternary carbon centers by alkylation of benzamide derivatives.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30401829.
- Also identified by DOI 10.1038/s41467-018-07069-1 and PMC identifier 6219510.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Selective creation of quaternary carbon centers has been a long-standing challenge in synthetic chemistry. We report here the chromium-catalyzed, para-selective formation of arylated quaternary carbon centers by alkylative reactions of benzamide derivatives with tertiary alkylmagnesium bromides at room temperature. The reaction, which was enabled by a low-cost chromium(III) salt combined with trimethylsilyl bromide, introduces a sterically bulky tertiary alkyl scaffold on the para-position of benzamide derivatives in a highly selective fashion without either isomerization of the tertiary alkyl group or formation of ortho-alkylated byproducts. Forming low-valent Cr species in situ by reaction of CrCl<sub>3</sub> with t-BuMgBr accompanied by evolution of hydrogen can be considered, which serves as reactive species to promote the reaction. The para-alkylation likely occurs via a radical-type nucleophilic substitution of imino-coordination benzimidate intermediate.