Ruthenium-Catalyzed Reductive Coupling of 1,3-Enynes and Aldehydes by Transfer Hydrogenation: anti-Diastereoselective Carbonyl Propargylation

Under the conditions of ruthenium-catalyzed transfer hydrogenation employing isopropanol as a source of hydrogen, isopropoxy-substituted enyne 1b and aldehydes 3a-3l engage in reductive coupling to provide products of propargylation 4a-4l with good to complete levels of anti-diastereoselectivity. The unprotected tertiary hydroxy moiety of isopropoxy enyne 1b is required to enforce diastereoselectivity. Deuterium-labeling studies corroborate reversible enyne hydrometalation in advance of carbonyl addition. As demonstrated in the conversion of 4f-h and 4k to 5f-h and 5k, the isopropoxy group of the product is readily cleaved upon exposure to aqueous sodium hydroxide to reveal the terminal alkyne.