Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 141, Issue 9, Pages 3901-3909Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b11838
Keywords
-
Categories
Funding
- National Institutes of Health [GM058160-17S1, R35-GM122483]
- Institute for Basic Science in Korea [IBS-R010-A1]
Ask authors/readers for more resources
Enantioenriched molecules bearing indole-substituted stereocenters form a class of privileged compounds in biological, medicinal, and organic chemistry. Thus, the development of methods for asymmetric indole alkylation is highly valuable in organic synthesis. Traditionally, achieving N-selectivity in indole alkylation reactions is a significant challenge, since there is an intrinsic preference for alkylation at C3, the most nucleophilic position. Furthermore, selective and predictable access to either N- or C3-alkylated chiral indoles using catalyst control has been a long-standing goal in indole functionalization. Herein, we report a ligand-controlled regiodivergent synthesis of N- and C3-alkylated chiral indoles that relies on a polarity reversal strategy. In contrast to conventional alkylation reactions in which indoles are employed as nucleophiles, this transformation employs electrophilic indole derivatives, N-(benzoyloxy)indoles, as coupling partners. N- or C3-alkylated indoles are prepared with high levels of regio- and enantioselectivity using a copper hydride catalyst. The regioselectivity is governed by the use of either DTBM-SEGPHOS or Ph-BPE as the supporting ligand. Density functional theory (DFT) calculations are conducted to elucidate the origin of the ligand-controlled regiodivergence.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available