A solvent-controlled switchable C-H alkenylation of 4-aryl-1H-pyrrole-3-carboxylates via a Pd(OAc)2 catalyzed oxidative Heck reaction was first realized. The corresponding C2 and C5 alkenylation products were obtained in good yields with high regioselectivities, respectively. The selective C5-alkenylation was successfully applied to the total synthesis of (±)-rhazinilam.

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.

Solvent-Controlled Switchable C-H Alkenylation of 4-Aryl-1H-pyrrole-3-carb-oxylates: Application to the Total Synthesis of ()-Rhazinilam. -For the first time, solvent controlled switchable alkenylation of 3,4-disubstituted pyrroles in moderate to good yields with excellent regioselectivities is developed. Toluene favors the selective C2-alkenylation, while DMF/DMSO mixtures lead to the C5--alkenylation products. The application of selective C5-alkenylation to the total synthesis of ()-rhazinilam (XIII) highlights the potential utility of this method. -(SU, Y.; ZHOU, H.; CHEN, J.; XU, J.; WU, X.; LIN, A.; YAO*, H.; Org. Lett. 16 (2014) 18, 4884-4887, http://dx.

The reaction tolerates a broad range of functionalized 3,4‐disubstituted pyrroles.