An Organocatalytic Cascade Approach toward Polysubstituted Quinolines and Chiral 1,4‐Dihydroquinolines–Unanticipated Effect of N‐Protecting Groups

Abstract

A matter of protection: The outcome of a divergent organocatalytic aza-Michael/aldol cascade process toward quinolines and 1,4-dihydroquinolines depends on the choice of the N-protecting group (see scheme; TEA = triethylamine, TMS = trimethylsilyl). Use of an electron-donating sulfonyl group results in an unanticipated aza-Michael/aldol/aromatization cascade to give polysubstituted quinolines (right). In contrast, chiral 1,4-dihydroquinolines are obtained with an electron-withdrawing sulfonyl group (left).

Recent Advances in Catalytic Asymmetric Aza‐Michael Addition Triggered Cascade Reactions

“…In 2012, Wang and co‐workers reported that C 2 ‐symmetric catalyst (2 R ,5 R )‐diphenylpyrrolidine C21 catalyzed the asymmetric aza‐Michael/aldol condensation cascade reaction of N ‐protected 2‐aminobenzaldehydes or ketones 88 with alkynyl aldehydes 24 (Scheme 33). [41] This approach with 1.0 mol% catalysts proceeded well to provide a variety of chiral 1,4‐dihydroquinoline derivatives 91 in good yields (70–99%) with excellent enantioselectivities (94–99% ee) in toluene at 0 °C. The mechanism model described in the scheme well explains the stereochemical configuration of the product obtained by the cascade reaction.…”

Organocatalytic transformations of alkynals, alkynones, propriolates, and related electron-deficient alkynes

“…Yu and Wang have described the synthesis of quinolones 24 or chiral 1,4-dihydroquinolines 25 by means of the addition of Ntosyl-2-aminobenzaldehyde 23 to propargyl derivatives 9 (Scheme 10). 13 The authors found that the selectivity 24/25 depended on the protecting group of the nitrogen. Thus, the use of aromatic sulfonamides containing electron-donating groups (such as methyl or methoxy) promoted the aromatization process through a dehydrationedeprotection sequence of the sulfonyl group (see right, Scheme 10).…”

Practical Pd(TFA)2-Catalyzed Aerobic [4+1] Annulation for the Synthesis of Pyrroles via “One-Pot” Cascade Reactions

“…To continue our research on C-N bond forming reactions [59][60][61][62][63][64][65], we sought to broaden dicarbonyl scope and study the application of the cycloaddition products found as key intermediates in the synthesis of biologically active compounds. Herein, we present a full account of our recent work on the Pd-catalyzed [4+1] annulation reaction.…”