Chromium-catalyzed para-selective formation of quaternary carbon centers by alkylation of benzamide derivatives. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Liu, Pei; Chen, Changpeng; Cong, Xuefeng; Tang, Jinghua; Zeng, Xiaoming
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 8
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07069-1
• Languages: English
• ISSNs: 2041-1723

Abstract

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 thepara -position of benzamide derivatives in a highly selective fashion without either isomerization of the tertiary alkyl group or formation ofortho -alkylated byproducts. Forming low-valent Cr species in situ by reaction of CrCl3 with t-BuMgBr accompanied by evolution of hydrogen can be considered, which serves as reactive species to promote the reaction. Thepara -alkylation likely occurs via a radical-type nucleophilic substitution of imino-coordination benzimidate intermediate. The selective installation of quaternary carbon substituents on arenes is a highly challenging synthetic goal. Here, the authors report a chromium-catalyzedpara -selective functionalization of benzamides with tertiary organometallic reagents under mild conditions.