NHC-Catalyzed Formal [2+2] Annulations of Allenoates for the Synthesis of Substituted Oxetanes

Abstract

An N-heterocyclic carbene (NHC)-catalyzed reaction of γ-substituted allenoates for the synthesis of substituted oxetanes has been developed. The method provides an approach to access substituted oxetanes in a single step and is the first example of an NHC-catalyzed formal [2+2]-annulation employing γ-substituted allenoates with trifluoromethyl ketones. Mechanistic and modeling studies provide a rationale for the divergence in reactivity observed compared to the analogous reaction using unsubstituted allenoates and inform a hypothesis to explain the observed diastereoselectivity under different reaction conditions.

Access to Allene‐Containing Molecules via Enantioselective Reactions of Azolium Cumulenolate Intermediates

“…When allenoate 6 was subjected to the standard conditions, no desired product 3 q was observed (Scheme 4 a). This result rules out the possibility of NHC-catalyzed Morita-Baylis-Hillman reaction of allenoate, [24] which is likely formed via protonation of cumulenolates in our reaction systems. [11a] Besides, the g-monosubstituted alkynal 7 could not undergo the reaction to give the desired allene product.…”

Access to α,α-difluoro(arylthio)methyl oxetanes from α,α-difluoro(arylthio)methyl ketones and trimethylsulfoxonium halides: scope, mechanism and applications

“…These results indicated that the oxirane species was the reaction intermediate. 15 It is worth mentioning that other reactions such as the further ring-opening 4 or ring-expansion 16 of oxetane 3a were completely inhibited because no other signals of the corresponding by-products were detected by 19 F-NMR analysis.…”

“…3 On the other hand, the inherent ring strain of oxetanes makes them reactive intermediates for further synthetic applications. 4 Therefore, the development of practical and efficient methods for the synthesis of new oxetane derivatives is an attractive research area in synthetic and medicinal chemistry.…”

Recent advances of N-heterocyclic carbenes in the applications of constructing carbo- and heterocyclic frameworks with potential biological activity

“…In 2018, Scheidt et al developed an asymmetric NHC-catalyzed [2 + 2] cycloaddition strategy for multi-substituted oxetanes 149 ( Scheme 49a ). 100 In 2019, Jin et al obtained challenging chromeno[4,3- b ]pyrrole derivatives containing four chiral centers with the catalysis of chiral NHC. 101 In the same year, Mhaske and coworkers prepared deoxy-cruciferane alkaloid scaffold 151, which was a class of biologically active skeletons, via intramolecular annulation reaction catalyzed by NHC C18 ( Scheme 49b ).…”