A Metal-Free Path to 2-Iodo-3-alkyl-1-arylbut-2-en-1-ones and Their Application to the Domino Synthesis of Functionalized 2H-Pyran-2-ones

Abstract

We report a metal-free selective synthesis of 2-iodo-3-alkyl-1-arylbut-2-en-1-ones from propargylic alcohols that is enabled by N-iodosuccinimide. A variety of substituted propargylic alcohols are amenable to delivering the selective 2-iodoenone products in very good yields. The utility of the α-iodoenone derivatives is further extended by developing an efficient, novel, and new synthetic methodology for the synthesis of 3,5,6trisubstituted 2H-pyran-2-ones. To the best of our knowledge, this protocol is the first of its kind to accomplish 3,5,6trisubstituted 2H-pyran-2-ones through an unprecedented domino (formation of two C−C bonds and one C−O bond) one-pot process via intermolecular Heck coupling, base-driven Michael addition, and base-mediated double bond isomerization followed by cyclo-condensation. This protocol showed good compatibility with a wide range of iodoenones (18 examples) and 2H-pyran-2-ones (42 examples). Mechanistic studies indicate that palladium is only involved in the Heck coupling; the base solely drives the rest of the steps.

One-Pot Dual C–C Bond-Forming Cascade Process via Suzuki Coupling and Intramolecular Cyclocondensation: An Access to Functionalized Naphthalenes

“…Our laboratory engaged in transition-metal-intimated cross-coupling reactions and the synthesis of polycyclic compounds using alkyne and alkene chemistry. − Recently, we disclosed α-iodoenone substrate synthesis from propargylic alcohols and its utility for the synthesis of functionalized 2 H -pyran-2-ones . In continuation of this, we came forward with a well-planned strategy to develop a methodology for the synthesis of naphthyl ketone derivatives by a domino single-pot process via C–C bond coupling (between C–I and C–B), a powerful tool for C–C bond formation. − Especially, the coupling provides the rapid formation of biaryls through smooth conversion of aryl boronic acids/esters and haloarenes.…”

Palladium-Catalyzed Acylation Strategies and Their Applications Towards Biologically Relevant Products

“…[25][26][27][28][29][30][31][32][33] In addition, palladium-catalyzed coupling strategies have been featured as the key transformations in successful syntheses of natural products and pharmaceutically active molecules. [34][35][36][37][38] An essential objective of organic chemistry is to develop novel and sustainable synthetic strategies for preparing intermediate products/synthons efficiently. In this regard, synthetic chemists are striving to design and develop novel catalysts, effective methodologies, and more ecologically friendly conditions.…”