An organocatalytic approach to enantiomerically enriched α-arylcyclohexenones and cyclohexanones

Abstract

The presence of a p-nitrophenyl group converts acetone into an excellent and versatile nucleophile in organocatalytic processes, able to react with α,β-unsaturated aldehydes affording β-substituted α-arylcyclohexenones via a Michael reaction/aldol reaction/dehydration sequence, which occurs in good yields, ee up to 96% and complete diastereoselectivity. The resulting compounds are excellent synthons for the diastereoselective preparation of a variety of synthetically useful polysubstituted cyclohexanones and derivatives.

Organocatalytic Michael Addition/Intramolecular Julia–Kocienski Olefination for the Preparation of Nitrocyclohexenes

“…The Julia–Kocienski reaction also went on the right track under conditions of entry 7 in Table (conditions A). However, Michael addition with aromatic enals presented erratic enantioselectivity when using the same conditions as those utilized for the aliphatic enals, owing to reversibility . Nevertheless, controlling reaction times and using LiOAc as additive, Michael adducts were obtained in good yields and enantioselectivities, both with electron-donating and electron-withdrawing groups (Table , entries 8–11).…”

Enantioselective Organocatalytic Michael/Aldol Sequence: Anticancer Natural Product (+)‐trans‐Dihydrolycoricidine

“…Natural (+) ‐trans ‐dihydrolycoricidine ( 6 ) has been the subject of four previous total syntheses 4. We were inspired by recent enantioselective organocatalytic approaches toward six‐membered carbocycles5a to develop a stepwise [3+3]‐type Michael/aldol sequence,5b–g involving an α‐nitrogen‐substituted acetone moiety reacting with an unsaturated aldehyde, as a possible rapid entry to the amaryllidaceae core. Such an approach would also open a valuable asymmetric entry to aminocyclitols, a large and expanding class of compounds with diverse biological activities 6.…”

Total Synthesis of the Natural Product (+)‐trans‐Dihydronarciclasine via an Asymmetric Organocatalytic [3+3]‐Cycloaddition and discovery of its potent anti‐Zika Virus (ZIKV) Activity

“…Natural (+)‐ trans ‐dihydronarciclasine 1 has been the subject of three prior asymmetric syntheses,– three racemic syntheses,– and the compound has also been the subject of semi‐synthesis via selective hydrogenation of narciclasine 3 . We were inspired by recent enantioselective organocatalytic approaches toward six member carbacycles to develop a stepwise [3+3]‐type Michael‐aldol sequence,– involving an α‐nitrogen‐substituted acetone moiety reacting with an unsaturated aldehyde, as a rapid entry to the amaryllidaceae core. Such an approach proved successful in our recent synthesis of alkaloid 2 , which provided access to the natural product and structural analogs that permitted investigation of the antiviral activity against herpes viruses …”