Methyltrifluoromethanesulfonate Catalyst in Direct Nucleophilic Substitution of Alcohols; One-Pot Synthesis of 4H-Chromene Derivatives

三氟甲磺酸甲酯催化剂在醇的直接亲核取代反应中的应用;4H-色烯衍生物的一锅法合成

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Abstract

The catalytic activity of methyltrifluoromethanesulfonate (MeOTf) has been explored toward direct nucleophilic substitution of the hydroxyl group of nonmanipulated alcohols such as benzylic, allylic, propargylic, and tertiary alcohols with a wide range of uncharged nucleophiles such as 1,3-dicarbonyl compounds, amides, alkynes, and indoles to generate functionalized 1,3-dicarbonyl compounds, amides, alkynes, and indoles, respectively. Thus, the present protocol defines an alternate pathway to construct new C-C, C-N, and C-O bonds with the formation of water as the byproduct under mild conditions without any acids or metals. A completely different mechanism was established through several control experiments to explain the reaction methodology. As an application of the reported protocol, 1H-indene derivatives have been synthesized in one pot when benzylic alcohols were subjected to react with internal alkynes. The scope of the reaction has been further extended toward a tandem benzylation-cyclization-dehydration of 1,3-dicarbonyl compounds with 2-hydroxybenzyl alcohols, which furnish biologically important 4H-chromene derivatives.

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