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

Abstract

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)(SiR)(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.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…The regioselectivity switch towards more distal, δ-position was possible by means of catalyst design ( Scheme 175B ). 1107 Hartwig discovered, in accordance with his previous work, that while using a Rh-catalyst with previously employed phenanthroline or common diphosphine ligands, such as BINAP or SEGPHOS, silylation occurs selectivity at 3-position. However, quite unexpectedly, addition of large bite angle Xanthpos ligand drastically altered the outcome of this C–H activation, directing the metallation event at 4-position and thus providing 6-membered oxasilolanes in good yields (around 70%).…”

Iridium-catalyzed silylation of unactivated C–H bonds

“…For example, we considered whether the process could form 1,4 diols or 1,2 diols. The formation of 1,4 diols by functionalization of a primary CeH bond in preference to the formation of 1,3 diols by functionalization of a secondary CeH bond was achieved by changing the catalyst from the iridium-phenanthroline system to a rhodium complex ligated by the bisphosphine Xantphos [27]. Dr. Li investigated rhodium catalysts for this process because we had shown previously that rhodium complexes of bisphosphines catalyze the enantioselective silylation of aryl CeH bonds [28].…”

“…Competition experiments prove the preferential activation of methyl CeH bonds over methylene CeH bonds[25].Scheme 8. d-C-H bond silylation of hydrosilyl ethers catalyzed by the combination of rhodium andxantphos generates 1,4-diols after oxidation and can be applied to the hydroxylation of complex architectures[27].…”

“…Relative computed transition-state energies for the CeH bond-cleavage and CeSi bond-forming elementary reaction steps of rhodium-catalyzed silylation of primary and secondary CeH bonds[27].…”

Mechanism and Diastereoselectivity of [3+3] Cycloaddition between Enol Diazoacetate and Azomethine Imine Catalyzed by Dirhodium Tetracarboxylate: A Theoretical Study

“…Furthermore, compared with conventional carbene intermediates (acceptor or acceptor/acceptor substitutes), donor/acceptor‐substituted rhodium–carbenes are more stable because of the presence of the donor group, which makes rhodium–carbenes highly regio‐ and stereoselective . Therefore, various rhodium catalysts have been widely applied in a variety of organic syntheses, such as asymmetric cyclization reactions, the arylation of phospholene oxides, and the regioselective silylation of alkyl C–H bonds . In a word, rhodium catalysis is a powerful protocol for producing carbo‐ and heterocycles …”