3 years ago

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

Regioselective Silylation of Alkyl
C–H Bonds for the Synthesis of 1,4-Diols
Caleb Karmel, Bijie Li, John F. Hartwig
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.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b11964

DOI: 10.1021/jacs.7b11964

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.