Synthesis of β-sulfinyl cyclobutane carboxylic amides via a formal α to β sulphoxide migration process

Abstract

An original tandem reaction consisting of a thermal elimination–addition process was developed.

Metal-free synthesis of an estetrol key intermediate under intensified continuous flow conditions

“…44,57 The thermolysis of five-membered sulfinylcycloketones was already reported. [28][29][30][31][32][33][34][35] While sometimes characterized by a radical mechanism 58 instead of an internal concerted elimination, 57 thermolysis concomitantly releases an enone and a sulfenic acid, the last one could be simply trapped to avoid an α to β sulfoxide migration process 59 and/or an alkene isomerization, thus potentially decreasing the selectivity toward the targeted product (Fig. 4).…”

β‐N‐Heterocyclic Cyclobutane Carboximides: Synthesis through a Tandem Base‐Catalyzed Amidation/aza‐Michael Addition Protocol and Facile Transformations

“…One of the challenges in this approach lies in the controlled preparation and manipulation of esters of cyclobutene‐1‐carboxylic acid [18] . We recently described the in‐situ generation of a cyclobutene carboxamide intermediate (from α‐sulfinyl cyclobutene‐1‐carboxylic amides) which underwent efficient thia‐Michael addition [19] …”

“…[18] We recently described the in-situ generation of a cyclobutene carboxamide intermediate (from α-sulfinyl cyclobutene-1-carboxylic amides) which underwent efficient thia-Michael addition. [19] On this premise, in continuation of our interest in the chemistry of aminocyclobutanes, [20] we envisaged that a transient cyclobutene carboxamide could be generated by coupling the parent acid with a nitrogen reagent 2 then could undergo an aza-Michael addition reaction with a second equivalent of 2 to generate a β-amino cyclobutane carboxamide 3 under mild organocatalytic conditions (Scheme 1). Herein, we disclose our findings using the particular case where benzoxazolones are the reaction partners; this leads to novel ACBC derivatives featuring both an N-heterocyclic function and a carboxyl group activated in the form of a carboximide, which facilitates further transformations of the carboxylic center.…”