A Trialkylphosphine-Derived Palladacycle as a Catalyst in the Selective Cross-Dimerization of Terminal Arylacetylenes with Terminal Propargyl Alcohols and Amides

Abstract

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-κ2-O,O-OAc)(κ2-C,P-(t-Bu)2PCH2C(Me)2CH2)]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-κ2-C1,C1-bound acetylide ligand. This complex is observed during the catalytic reaction and is a competent precatalyst.