N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

Abstract

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

Dichotomous Selectivity in Indium-Mediated Aza-Barbier-Type Allylation of 2-N-Acetyl Glycosyl Sulfinylimines in Brine: Convenient Access to Potent Anti-Influenza Agents

“…Although the allylation of pentosylamine has been achieved using indium metal in methanol, stereocontrolled allylation of glycosylamines remains a daunting challenge in aqueous media. Additionally, the diastereoselective allylation of chiral auxiliary-derived imines has received attention. , The reaction can be carried out stereoselectively and provides enantiopure amines effectively with the use of appropriate chiral auxiliaries. Considering the stability and reactivity of N - tert -butanesulfinyimines, we decided to use O -protected tautomeric open-chain 2- N -acetyl glycosyl sulfinylimines as substrates to investigate indium-mediated aza-Barbier-type allylation.…”

Synthetic Approach toward Enantiopure Cyclic Sulfinamides

“…In order to explore the counterion effect we switched to hexamethyldisilamide bases conveniently available as THF solutions (Table , entries 2–4). Reaction with LiHMDS reflected the usual propensity of sulfinamides for N -alkylation manifested in formation of azetidine 5a . While KHMDS produced a dramatically increased amount of isomerization, NaHMDS performed similarly to NaH.…”

Desymmetrization of Cyclohexadienones through Phase-Transfer-Catalyzed Stereoselective Intramolecular Aza-Michael Addition with Chiral Sulfinamide Nucleophiles

“…1,2 These reactions have been extended to the synthesis of numerous biologically crucial chiral cyclic compounds. 3,4 For example, Fustero and del Pozo described the use of tethered chiral tertbutyl sulfinamides as nucleophiles in stereoselective intramolecular aza-Michael reactions, which produced various nitrogen-containing heterocycles with excellent stereocontrol (Scheme 1a). 5 These cyclic compounds served as useful building blocks for the asymmetric synthesis of natural products, such as (−)-dihydrocuscohygrine and (−)-pinidinol.…”