A method for the selective cross-dimerization of terminal aryl alkynes with propargyl alcohols to afford linear (E)enynol products is reported. The complex [Pd(μ-κ 2 -O,O-OAc)(κ 2 -C,P-(t-Bu) 2 PCH 2 C(Me) 2 CH 2 )] 2 selectively affords (E)-5-aryl-2-en-4-yn-1-ol products in good yields under mild conditions with high chemo-, regio-, and stereoselectivity. In contrast, previously reported examples of this reaction afford the branched 4-aryl-2-hydroxymethanol-1-buten-3-yne. Propargyl amides are also selectively cross-dimerized, but with lower regioselectivity for the linear enyne. The method has been applied to the synthesis of (E)-5-phenyl-2-penten-4-yn-1ol, which is a precursor to type 2 diabetes drug candidate NNC 61-4655, in 72% yield from phenylacetylene and propargyl alcohol. The palladacycle precatalyst reacts with aryl alkynes to afford the first example of a dimeric palladacycle complex with a μ-κ 2 -C 1 ,C 1 -bound acetylide ligand. This complex is observed during the catalytic reaction and is a competent precatalyst.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.