Rhodium-Catalyzed Regioselective Silylation of Alkyl C–H Bonds for the Synthesis of 1,4-Diols

A rhodium-catalyzed intramolecular silylation of alkyl C–H bonds has been developed that occurs with unusual selectivity for the C–H bonds located δ to the oxygen atom of an alcohol-derived silyl ether over typically more reactive C–H bonds more proximal to the same oxygen atom. (Hydrido)­silyl ethers, generated in situ by dehydrogenative coupling of tertiary alcohols with diethylsilane, undergo regioselective silylation at a primary C–H bond δ to the hydroxyl group in the presence of [(Xantphos)­Rh­(Cl)] as catalyst. Oxidation of the resulting 6-membered oxasilolanes generates 1,4-diols. This silylation and oxidation sequence provides an efficient method to synthesize 1,4-diols by a hydroxyl-directed, aliphatic C–H bond functionalization reaction and is distinct from the synthesis of 1,3-diols from alcohols catalyzed by iridium. Mechanistic studies show that the rhodium-catalyzed silylation of alkyl C–H bonds occurs with a resting state and relative rates for elementary steps that are significantly different from those for the rhodium-catalyzed silylation of aryl C–H bonds. The resting state of the catalyst is a (Xantphos)­Rh­(I)­(SiR3)­(norbornene) complex, and an analogue was synthesized and characterized crystallographically. The rate-limiting step of the process is oxidative addition of the δ C–H bond to Rh. Computational studies elucidated the origin of high selectivity for silylation of the δ C–H bond when Xantphos-ligated rhodium is the catalyst. A high barrier for reductive elimination from the six-membered metalacyclic, secondary alkyl intermediate formed by cleavage of the γ C–H bond and low barrier for reductive elimination from the seven-membered metalacyclic, primary alkyl intermediate formed by cleavage of the δ C–H accounts for the selective functionalization of the δ C–H bond.