Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

Abstract

The enantioselective intermolecular C2-allylation of 3-substituted indoles is reported for the first time.This directing group-free approach relies on ac hiral Ir-(P,o lefin) complex and Mg(ClO 4 ) 2 Lewis acid catalyst system to promote allylic substitution, providing the C2-allylated products in typically high yields (40-99 %) and enantioselectivities (83-99 %e e) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2allylation, rather than C3-allylation followed by in situ migration. Steric congestion at the indole-C3 position and improved p-p stackingi nteractions have been identified as major contributors to the C2-selectivity. Scheme 1. Intermolecular indole C2-allylation.

Recent Advances in Metal‐Catalyzed Functionalization of Indoles

“…In 2020, You, Unsworth and co‐workers discovered a C2−H enantioselective allylation of indoles with allylic alcohols catalyzed by iridium in the presence of Carreira ligand (Scheme 24). [45] Regioselectivity is achieved by the C3‐substituent on the indole, while in its absence C3−H allylation occurs. The catalytic system involves [Ir(cod)Cl] 2 (4 mol%), a chiral phosphoramidate/olefin ligand [46] (16 mol%) and Mg(ClO 4 ) 2 (0.25 equiv.)…”

“… Iridium‐catalyzed C2−H enantioselective allylation of indoles by Unsworth and You [45] …”

Rhodium‐Catalyzed Chemodivergent Regio‐ and Enantioselective Allylic Alkylation of Indoles

“…Transition‐metal‐catalyzed asymmetric allylation [4] of indoles provides a powerful method to synthesize chiral C3‐ and N1‐allylindoles. Despite many reports on chiral C3‐allylindole synthesis, [5, 6] highly branched‐ and enantioselective allylation of indoles from monosubstituted allylic precursors could be achieved by You and co‐workers with iridium and π‐acidic phosphoramidite ligands, [7a,b,c] in which highly reactive Ir III /π‐allyl intermediates are involved (Scheme 1 b, left). Shen and Dong reported asymmetric allylation of indoles with alkynes in the presence of a chiral Rh complex [7d] .…”

Cp*Co(III)‐Catalyzed Dehydrative C2‐Prenylation of Pyrrole and Indole with Allyl Alcohols

“…Over the last decade, CÀ H functionalization, in particular transformations under cobalt catalysis have been found to be one of the straightforward approaches for the functionalization of indoles and pyrroles since it requires no substrate pre-functionalization. [8] Recently, several directing groups based C2-allylation of indoles and pyrroles have been developed using various directing groups under Rh, [9] Mn, [10] Co, [11] Ru, [12] Ir, [13] and Pd [14] catalytic systems using different allylating agents. However, the often-found limitations are the use of Ag(I)-co-catalyst, expensive directing groups, and unwanted alkene isomerization during the deprotection.…”