Direct, Redox-Neutral Prenylation and Geranylation of Secondary Carbinol C–H Bonds: C4-Regioselectivity in Ruthenium-Catalyzed C–C Couplings of Dienes to α-Hydroxy Esters

Abstract

The ruthenium catalyst generated in situ from Ru3(CO)12 and tricyclohexylphosphine, PCy3, promotes the redox-neutral C-C coupling of aryl substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C-H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetallated reagents, and is the first example of C4-regioselectivity in catalytic C-C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene-carbonyl oxidative coupling.

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…66–68 Mechanistic studies corroborate a catalytic mechanism involving diene-carbonyl oxidative coupling to form an oxaruthenacycle. The transfer of hydrogen from the secondary alcohol reactant mediates transfer hydrogenolysis to release the products of C-C coupling and regenerate the activated ketone to close the catalytic cycle.…”

“…The regioselectivity of C-C bond formation for the diene C4-position is unique among diene-carbonyl reductive couplings. 41,69 Beyond α-hydroxy esters, 66 these conditions are applicable to 3-hydroxy-2-oxindoles 67 and secondary alcohols substituted by certain heteroaromatic moieties. 68 In the latter case, the putative oxaruthenacycle intermediate was isolated, characterized and reversible metalacycle formation was demonstrated through experiments involving diene exchange.…”

Ruthenium-catalysed alkoxycarbonylation of alkenes with carbon dioxide

“…Functionalized alcohols with halide and ether groups were well tolerated too (entries [20][21][22][23] Control experiments. To gain more insight into this rutheniumcatalysed C-C bond formation 32,33 with carbon dioxide, a series of control experiments were performed. Initially, the reaction of carbon dioxide and methanol under catalytic conditions without any olefin present was studied (Fig.…”

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…[66][67][68] Mechanistic studies corroborate a catalytic mechanism involving diene-carbonyl oxidative coupling to form an oxaruthenacycle. The transfer of hydrogen from the secondary alcohol reactant mediates transfer hydrogenolysis to release the products of C-C coupling and regenerate the activated ketone to close the catalytic cycle.…”