Solvent-Controlled C2/C5-Regiodivergent Alkenylation of Pyrroles
Youla Su1, Shang Gao1, Yue Huang1
1State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009 (P. R. China).
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 CH 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.
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