Iridium Catalyzed Enantioselective Intermolecular Indole C2-Allylation

TY - JOUR

T1 - Iridium Catalyzed Enantioselective Intermolecular Indole C2-Allylation

AU - Rossi-Ashton, James A

AU - Clarke, Aimee K

AU - Donald, James R

AU - Zheng, Chao

AU - Taylor, Richard J K

AU - Unsworth, William Paul

AU - You, Shu-Li

N1 - © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2020/5/4

Y1 - 2020/5/4

N2 - The enantioselective intermolecular C2-allylation of 3-substituted indoles is reported for the first time. This directing group-free approach relies on a chiral Ir-(P, olefin) complex and Mg(ClO4)2 Lewis acid catalyst system to promote allylic substitution, providing the C2-allylated products in typically high yields (40-99%) and enantioselectivities (83-99% ee) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2-allylation, rather than C3-allylation followed by in situ migration. Steric congestion at the indole-C3 position and improved π-π stacking interactions have been identified as major contributors to the C2-selectivity.

AB - The enantioselective intermolecular C2-allylation of 3-substituted indoles is reported for the first time. This directing group-free approach relies on a chiral Ir-(P, olefin) complex and Mg(ClO4)2 Lewis acid catalyst system to promote allylic substitution, providing the C2-allylated products in typically high yields (40-99%) and enantioselectivities (83-99% ee) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2-allylation, rather than C3-allylation followed by in situ migration. Steric congestion at the indole-C3 position and improved π-π stacking interactions have been identified as major contributors to the C2-selectivity.

U2 - 10.1002/anie.202001956

DO - 10.1002/anie.202001956

M3 - Article

C2 - 32091146

SN - 1433-7851

VL - 59

SP - 7598

EP - 7604

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 19

ER -