Direct Catalytic Asymmetric and Regiodivergent N1‐ and C3‐Allenylic Alkylation of Indoles
Taochun Zha, Jiehui Rui, Zhihan Zhang, Dongqiang Zhang, Zhirong Yang, Peiyuan Yu, Yingcheng Wang, Fangzhi Peng, Zhihui Shao
Abstract
Abstract Herein we report a Pd‐catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H‐indoles by employing P‐chiral BIBOP‐type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs 2 CO 3 at elevated temperatures in MeCN, N1‐alkylated indoles bearing axial chirality with a stereocenter non‐adjacent (β) to the nitrogen are produced in good yields with high enantioselectivity and complete N1‐regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K 2 CO 3 at room temperature in CH 2 Cl 2 , chiral C3‐alkylated indoles can also be obtained. Notably, we introduce a new class of tri‐substituted allenylic electrophiles that proceeded through different pathways from di‐substituted allenylic electrophiles.