Enantioselective Organocatalytic Intramolecular Aza‐Diels–Alder Reaction

Abstract

A highly efficient catalytic enantioselective intramolecular Povarov reaction was developed with primary anilines as 2-azadiene precursors. A wide variety of angularly fused azacycles were obtained without column chromatography in high to excellent yields and with excellent diastereo- and enantioselectivity (d.r.>99:1 and up to e.r. 99:1). Furthermore, the catalyst loading could be lowered to 1 mol %, and the obtained azacycles could be used as key intermediates for further transformations to generate additional molecular diversity.

Intermolecular [3+3] ring expansion of aziridines to dehydropiperi-dines through the intermediacy of aziridinium ylides

“…Piperidines rank as the most prominent N-heterocyclic pharmacophore in current drugs on the market, appearing in~55% of all FDA-approved drugs containing at least one N-heterocycle, as well as in numerous bioactive natural products 3 . Convergent methods that unite multiple reactive fragments, particularly hetero-[4+2] cycloadditions, deliver substituted dehydropiperidines in enantioenriched form [21][22][23][24][25][26][27][28][29][30][31] ; however, critical substrate and/or catalyst control over regio-and stereoselectivity is challenging and often results in narrow scope. Traditional preparations of stereodefined piperidines using intramolecular S N 2-type reactions require selective installation of functional groups prior to ring closure, resulting in lower efficiency, modularity, and step economy as the desired target's complexity increases 3 .…”

Highly Diastereo‐ and Enantioselective Synthesis of Cyclohepta[b]indoles by Chiral‐Phosphoric‐Acid‐Catalyzed (4+3) Cycloaddition

“…Other drying agents were evaluated, but 4 MS provided the best results in terms of both yield and enantioselectivity (entry 2v s. [5][6][7][8]. Diversely substituted carbamates reacted with 1a,b ut the best results were obtained with Cbz-protected dienamines (entry 2v s. [10][11][12].…”

“…As part of ap rogram directed toward the stereoselective synthesis of heterocycles, [10] we recently described an efficient enantioselective synthesis of trisubstituted cyclopenta-[b]indoles [10c] through ac hiral-phosphoric-acid-catalyzed (3+ +2) cycloaddition between alkylideneindoleninium ions generated in situ from indolylarylmethanols [11] and enecarbamates as dienophiles. [12,13] We also reported that chiral phosphoric acid catalysts were able to efficiently catalyze asymmetric nitroso-Diels-Alder reactions with 1,3-diene-1carbamates.…”

Académie des Sciences Prizes: M. Taillefer, G. Masson, L. Peng, D. Matt / Horst Dietrich Hardt Prize: L. H. Gade / Yamada–Koga Prize: J.‐E. Bäckvall

“…Masson and her group are interested in the development of new catalytic methods, in particular asymmetric organocatalysis, photoredox catalysis, and asymmetric hypervalent iodine catalysis. She has reported in Angewandte Chemie on an enantioselective organocatalytic intramolecular aza‐Diels–Alder reaction, and in Chemistry—A European Journal on Brønsted catalysis…”