Azetines are valuable 4-membered nitrogen-containing heterocycles with unique reactivity and useful synthetic applications. Recent methods to access these compounds and a comprehensive review of their application as intermediates is presented.
Four-membered nitrogen-containing heterocycles are highly desirable functional groups with synthetic and biological applications. Unsaturated 4-membered N-heterocycles, 1- and 2-azetines, are historically underexplored, but have recently been gaining increased interest due to the development of new synthetic methods to access these compounds, and to their potential as reactive intermediates. This review covers new strategies for the synthesis of 1- and 2-azetines with a particular focus on advances made since 2018. Additionally, the use of these compounds as intermediates to access other heterocycles (3- to 6-membered) and complex products is comprehensively discussed.
We disclose an intermolecular 1,2-aminoarylation of alkenes using aryl sulfinamide reagents as bifunctional amine and arene donors. This reaction features excellent regio- and diastereoselectivity on a variety of activated and unactivated substrates. Using a weakly oxidizing photoredox catalyst, a sulfinamidyl radical is generated under mild conditions and adds to an alkene to form a new C–N bond. A desulfinylative Smiles-Truce rearrangement follows to form a new C–C bond. In this manner, biologically active arylethylamines and valuable building blocks can be rapidly assembled from abundant alkene feedstocks. Additionally, we demonstrate that chiral information from the sulfinamide can be transferred via rearrangement to a new carbon stereocenter in the product, thus advancing development of traceless asymmetric alkene difunctionalization methodologies.
Macrocyclic, dimeric lactones have known pharmacological activities that make them attractive synthetic targets but are typically synthesized following an iterative approach. Herein, we report a visible light-mediated approach to macrocyclic dimers that allows access to 1- and 2-azetine-containing dimeric lactones. Notably, up to 30-membered macrocycles are formed following this strategy that results in 1-azetine dimers via four consecutive triplet energy transfers, while 2-azetines are formed in a sequence relying on two consecutive triplet energy transfers. Computational investigations provide important insights into the reaction mechanism, suggesting that intermolecular [2+2]-cycloadditions are preferred under non-standard Curtin-Hammett conditions over the corresponding intramolecular reaction.
Macrocyclic, dimeric lactones have known pharmacological activities that make them attractive synthetic targets but are typically synthesized following an iterative approach. Herein, we report a visible light-mediated approach to macrocyclic dimers that allows access to 1- and 2-azetine-containing dimeric lactones. Notably, up to 30-membered macrocycles are formed following this strategy that results in 1-azetine dimers via four consecutive triplet energy transfers, while 2-azetines are formed in a sequence relying on two consecutive triplet energy transfers. Computational investigations provide important insights into the reaction mechanism, suggesting that intermolecular [2+2]-cycloadditions are preferred under non-standard Curtin-Hammett conditions over the corresponding intramolecular reaction.
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