Chiral phosphoramide-catalyzed enantioselective synthesis of 2,3′-diindolylarylmethanes from indol-2-yl carbinols and indoles

Abstract

We present the first asymmetric reaction of indol-2-yl carbinols with indole derivatives catalyzed by chiral phosphoramides for the enantioselective synthesis of 2,3'-diindolylarylmethanes in excellent yields of over 90% as well as high enantioselectivity of up to 96% ee.

Overview on the Recent Strategies for the Enantioselective Synthesis of 1, 1‐Diarylalkanes, Triarylmethanes and Related Molecules Containing the Diarylmethine Stereocenter

“…[69] In 2014, Qi et al described Binol derived chiral phosphoramide (28 a)-catalyzed asymmetricF riedel-Crafts alkylation of indol-2-yl carbinols with indoles for the asymmetrics ynthesis of 2, 3'-diindolyl aryl methanes (Scheme39a). [70] Interestingly,t he authors observedt hat the chirality of the products obtained from the 3, 3' substituted binol phosphoramide were opposite from that obtained from unsubstituted Binol phosphoramide. Also unsubstituted Binol phosphoramide gave higher enantioselectivity.T he enantioselectivity in non-polar solvents were higher than in polar solvents which indicated astrong ion pairing interaction between the developed indole iminium ion or the benzhydryl type ion with the phosphoramide anion.…”

New Perspectives in the Indole Ring Functionalization using 2‐Indolylmethanols

“…The reaction of 2‐indolylmethanes with aromatic derivatives has been mainly studied in the search of new procedures to access unsymmetrical bisindolylmethanes, and more generally triarylmethanes embedding the indole moiety . The first asymmetric synthesis of 2,3′‐bisindolylmethanes 77 has been carried out by reaction of 2‐indolylmethanols 75 with indoles in the presence of chiral phosphoramide 76 (Scheme ) . The chemical yields of the resulting adducts 77 are very good and the level of enantioselectivity recorded is rather satisfactory.…”

Bi(OTf)3 Catalyzed Solvent Free Approach to Unsymmetrical Diaryl(2‐indolyl)methanes through 1,6‐Conjugate Addition of 3‐Substituted Indoles to para‐Quinone Methides

“…Recently, Feng and co‐workers disclosed a nickel catalyzed enantioselective addition of skatole derivatives to β,γ‐unsaturated‐α‐ketoesters . In addition, Han's group reported chiral phosphoramide catalyzed formation of 2,3‐diindolylarylmethanes and 2‐indole substituted 1,1‐diarylalkanes from indol‐2‐yl‐carbinols. Hu and Zhao's group realized a highly enantioselective Friedel‐Crafts alkylation of 3‐substituted indoles to β,γ‐unsaturated α‐ketimino esters .…”