title: Solvent-Controlled C2/C5-Regiodivergent Alkenylation of Pyrroles.
abstract: A solvent-controlled C2/C5-selective alkenylation of 3,4-disubstituted pyrroles has been developed. The C3 substituent of pyrroles proved crucial to the regioselectivity. Substrates bearing directing groups at the C3 position exhibited excellent C2-selectivities in chelation-assisted CH activation in toluene or 1,4-dioxane. However, a DMSO/DMF solvent system could override the chelation effect of weak directing groups, such as carboxylate and carbonyl groups, favoring instead regioselectivity towards the more electron-rich C5 position. A series of 3-carboxylate and 3-carbonyl pyrroles were tested and showed moderate to good yields with good regioselectivities for both C2- and C5-alkenylation process.
authors.affiliation: State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009 (P. R. China).
authors.forename: Youla
authors.initials: Y
authors.lastname: Su
authors.affiliation: State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009 (P. R. China).
authors.forename: Shang
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009 (P. R. China).
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009 (P. R. China). hyao@cpu.edu.cn.
authors.forename: Aijun
authors.initials: A
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009 (P. R. China). ajlin@cpu.edu.cn.
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
keywords: CH activation; alkenes; pyrroles; regioselectivity; solvent effects