Substituent effects on regioselective intramolecular oxidation of unactivated C-H bonds: Stereoselective synthesis of substituted tetrahydropyrans

Man Kin Wong, Nga Wai Chung, Lan He, Dan Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

33 Citations (Scopus)


Our previously reported intramolecular δ-selective C-H bond oxidation by dioxiranes, generated in situ from activated ketones, offers a novel approach to the synthesis of tetrahydropyrans. To synthesize substituted tetrahydropyrans in a stereoselective manner, we examined the effects of alkyl, nitrogen, and oxygen substituents at the α-,β-, and γ-sites of ketones on the stereoselectivities of intramolecular C-H bond oxidation reactions. Ketones 1-4 with a methyl group at the α-, β-, or γ-site showed the diastereo-selectivities that agreed with the trans/cis ratio predicted by considering steric interactions in the transition states. Furthermore, ketones 5 and 6 carrying a bulky phthalimido group at the α- and the β-sites, respectively, exhibited excellent stereoselectivity, each affording only one diastereomer. However, ketones 9 and 10 bearing β-oxygen substituents gave reversed stereoselectivity as compared to those with β-alkyl or nitrogen substituents, possibly because of the hydrogen bonding interaction in the transition state. For ketones 12 and 13, both bearing methyl and silyloxy groups, the hydrogen bonding interaction was probably more important than the steric effect on the diastereoselectivity of intramolecular oxidation of C-H bonds.
Original languageEnglish
Pages (from-to)158-162
Number of pages5
JournalJournal of the American Chemical Society
Issue number1
Publication statusPublished - 8 Jan 2003
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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