Palladium‐Catalyzed Regio‐ and Stereoselective Cross‐Addition of Terminal Alkynes to Ynol Ethers and Synthesis of 1,4‐Enyn‐3‐ones

Abstract

Conjugated enynes, enol ethers, and enynones are versatile building blocks that can be elaborated by a wide variety of synthetic transformations. The selective synthesis of such units is a prerequisite for their effective utilization. The synthesis of conjugated 2-phenoxyenynes through a palladium-catalyzed cross-addition of terminal alkynes to phenylethynyl ethers (hydroalkynylation) is now presented. The reaction is highly regio-, stereo-, and chemoselective, and shows excellent tolerance toward functional groups. The addition further features very mild reaction conditions (room temperature) and an inexpensive catalytic system (without a ligand and with a cheaply available Pd catalyst). The thus synthesized enynyl ethers with allylic hydroxy tethers, which survived the reaction, were shown to be ready precursors for valuable 1-en-4-yn-3-ones.

A Sequential Activation of Alkyne and C–H Bonds for the Tandem Cyclization and Annulation of Alkynols and Maleimides through Cooperative Sc(III) and Cp*-Free Co(II) Catalysis

“…These methods are distinctive from earlier alkylation (Michael addition) and 1,1-annulation (for spiro adducts) with the same maleimides . We show herein, in continuation of our efforts to unearth the novel reactivities of functionalized alkynes, the annulation of the maleimides with alkyne through a prior in situ cyclization with an internal hydroxyl group (Scheme e). Liu and Li previously reported the RhCp*-catalyzed alkyne annulation after similar cyclization .…”

Regioselective Palladium-Catalyzed Heterocyclization–Sonogashira Coupling Cascades from 2-Alkynylbenzamides and Terminal Alkynes: Experimental and DFT Studies

“…Alternative methods have also been developed for alkyne coupling, which avoid the need for a halide precursor or for a Cu cocatalyst. Thus, under Pd-catalyzed conditions, terminal alkynes have undergone conjugate addition to α,β-unsaturated carbonyl derivatives, − cross-addition to ynol ethers, and oxidative C sp2 –C sp coupling. − In a broader synthetic context, the general field of metal-catalyzed heterocyclization–coupling reactions (Scheme b) has been the subject of continuing attention because it provides access to functionalized heterocyclic structures with useful applications. The particular case of palladium-catalyzed heterocyclization–alkynylation cascades (Scheme c) is also known, − but it has received comparatively little attention despite its potential for the incorporation of alkynyl groups onto heterocyclic frameworks.…”

Gold-Catalyzed Alkynylative Meyer–Schuster Rearrangement

“…However, the corresponding alkynylative interception, termed as the “alkynylative” Meyer–Schuster rearrangement (Z = alkynyl), has remained elusive so far. Although the term “alkynylative Meyer–Schuster rearrangement” was originally coined by Reddy and co-workers, their efforts to develop the same was unsuccessful . In their case, instead of a Meyer–Schuster rearrangement, the reaction between alkynols and terminal alkynes under Pd catalysis resulted in syn -alkynopalladation ( Int I′ ) via [1,2]-migratory insertion from Int I (Scheme C, eq a).…”