Selective Synthesis\nof <i>Z</i>‑Michael\nAcceptors via Hydroalkylation of Conjugated Alkynes

Hydroalkylation of terminal alkynes is a powerful approach\nto the\nsynthesis of disubstituted alkenes. However, its application is largely\nunexplored in the synthesis of α,β-unsaturated carbonyls,\nwhich are common among synthetic intermediates and biologically active\nmolecules. The thermodynamically less stable <i>Z</i>-isomers\nof activated alkenes have been particularly challenging to access\nbecause of their propensity for isomerization and the paucity of reliable <i>Z</i>-selective hydroalkylation methods. We developed a highly <i>Z</i>-selective silver-catalyzed hydroalkylation of terminal\nconjugated alkynes using alkyl boranes as coupling partners. The reaction\nallows access to (<i>Z</i>)-α,β-unsaturated\nesters, secondary and tertiary alkyl amides, aryl amides, and alkyl\nand aryl ketones and tolerates a wide range of functional groups.\nThe reaction can be performed successfully in the presence of alkyl\nand aryl halides, esters, protected alcohols, and amines. The hydroalkylation\ninvolves the formation of an alkynylboronate complex followed by a\n1,2-metalate shift. This sequence of steps mechanistically constrains\nthe stereochemical outcome, which, together with mild reaction conditions,\nensures high <i>Z</i>-selectivity.