Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles

Abstract

A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This “designer acid catalyst”, which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2‐aryl‐substituted N‐unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3‐protonation and hydride‐transfer processes. Besides, bulky C2‐alkyl‐substituted N‐unprotected indoles are also suitable for this system.

Progresses in organocatalytic asymmetric dearomatization reactions of indole derivatives

“…In 2020, Song, Yu and coworkers established an organo-CADA reduction of C2-substituted indoles 169 in the presence of catecholborane 170, water and CPA (S)-C33, which generated C2-substituted indolines 171 in moderate to good yields and high enantioselectivities (Scheme 38). 72 In this reaction, the authors suggested that a new chiral B-H was generated in situ from CPA boron complex and water, whose acidity is higher than TsOH estimated by DFT calculations. Additionally, they performed DFT calculations on the possible reaction pathways and activation mode of the new chiral B-H on the substrate.…”

“…In the proposed transition state (TS-1), L-proline C35 acted as a bifunctional catalyst, which not only activated aldehydes or ketones 174 via enamine catalysis but also activated oxindol-1-ium intermediates via hydrogenbonding catalysis, thus facilitating a stereoselective addition Scheme 38 Organo-CADA reduction of C2-substituted indoles by Song, Yu and coworkers. 72 Scheme 39 Organo-CADA oxidation of C3,C2-substituted indoles by Jiang, Zhao and coworkers. 73 reaction between the two reaction partners to give products…”

Catalytic Asymmetric Transfer Hydrogenation of trans-Chalcone Derivatives Using BINOL-derived Boro-phosphates

“…In this previous work, a plausible mechanism suggested that the boro-phosphate could behave as a chiral bifunctional activator. There have been several additional asymmetric hydrogenation reactions utilizing the combination of CPAs and boranes. , On the basis of these successes, in this study, we describe the asymmetric hydrogenation of the CC bonds of trans -chalcone derivatives by chiral boro-phosphate catalysts (Scheme d).…”

Recent developments in enantio- and diastereoselective hydrogenation of N-heteroaromatic compounds

“…The chiral Brønsted acid was generated in situ from a chiral phosphoric acid (C 4 ) boron complex (CPAB) by interaction with water. 174 TsOH, a strong acid, had been previously used to protonate the C3 position of 2-alkylindoles forming an iminium salt. 175,176 Treatment with a suitable reducing agent allows for the conversion of the iminium into the corresponding indoline.…”