A Highly Enantioselective Catalytic Mannich Reaction of Indolenines with Ketones

Abstract

A range of polysubstituted indolenines (3H‐indoles) smoothly underwent an L‐proline‐catalyzed enantioselective Mannich reaction with various ketones in a highly regioselective manner to give structurally diverse 2‐acylmethylindolines in good yields with excellent ee. The current study provides a powerful approach for the transformation of unactivated five‐membered cyclic aldimines into optically active nitrogen‐containing heterocycles with high enantioselectivity.

Dialkylation of Indoles with Trichloroacetimidates to Access 3,3-Disubstituted Indolenines

“…This upfield chemical shift is consistent with literature reports of similar spiropiperidine-indanes [75]. In further support of this rationale, in structures where the C2 position of the pyrroline is unsubstituted [76], or there is no aromatic sulfonamide [77], no similar upfield shifts are observed in the 1 H NMR.…”

Indoline‐Based Constrained Peptidomimetic Motifs Obtained via the Joullié–Ugi Reaction of Indolenines

“…To our surprise, gem ‐dimethyl‐substituted indolenine 1a turned out to be rather unstable to isolation (including evaporation of chloroform following reaction work‐up). This finding, however, is in line with some literature reports where compound 1a was either acylated in situ or underwent rearrangement (methyl group migration) (from the more recent report by Cheng et al it was not clear if 1a was isolated as individual compound). Hence, 1a was used in the Joullié–Ugi reaction without purification (as it was deemed sufficiently pure according to TLC analysis), which led to moderate yields.…”

“…Indolenines ( 1 ) are an intriguing type of cyclic imines obtainable, among other methods, by the Fisher synthesis employing α,α‐disubstituted aldehydes . Indolenines have been further transformed via in situ reduction (to produce 3,3‐disubstituted indolines), enantioselective catalytic Mannich reaction, enantioselective Strecker reaction, or skeletal rearrangement, (Scheme ).…”

Rapid Assembly of Functionalised Spirocyclic Indolines by Palladium‐Catalysed Dearomatising Diallylation of Indoles with Allyl Acetate

“…Gratifyingly, we found that L -proline-catalysed Mannich reaction of acetone with three diallylindolinines ( 3 a , d , j ) gave the corresponding 3-aminoketones 14 a – c in good yield and with very high enantioselectivity. During the preparation of this manuscript, similar conditions were reported for the asymmetric Mannich reaction of closely related 3,3-disubstituted indolinines,32 so this reaction was not explored in further detail.…”