Zhang Ze-Xuan, Zhang Bing, Yuan Meng, Zhao Peng-Fei, Da Chao-Shan
Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, P. R. China.
State Key Laboratory of Applied Organic Chemistry, Key Lab of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000, P. R. China.
Org Lett. 2024 Aug 16;26(32):6819-6824. doi: 10.1021/acs.orglett.4c01970. Epub 2024 Aug 6.
With alanine as a transient directing group, Pd-catalyzed regioselective alkynylation at the indole C4-position was successfully established in a good yield. The total synthesis of the PAF antagonist demonstrated the synthetic utility of this protocol. The regioselectivity was explicitly proven by the prepared C4-selective palladacycle intermediate in the catalytic process and the DFT calculation of the energy barriers of C4- and C2-site-selective C-H activation of indole.
