Investigation on the Regioselectivities of Intramolecular Oxidation of Unactivated C−H Bonds by Dioxiranes Generated in Situ

Abstract

We found that dioxiranes generated in situ from ketones 1-6 and Oxone underwent intramolecular oxidation of unactivated C-H bonds at delta sites of ketones to yield tetrahydropyrans. From the trans/cis ratio of oxidation products 1a and 2a as well as the retention of the configuration at the delta site of ketone 5, we proposed that the oxidation reaction proceeds through a concerted pathway under a spiro transition state. The intramolecular oxidation of ketone 6 showed the preference for a tertiary delta C-H bond over a secondary one. This intramolecular oxidation method can be extended to the oxidation of the tertiary gamma' C-H bond of ketones 9 and 10. For ketone 11 with two delta C-H bonds and one gamma' C-H bond linked respectively by a sp(3) hydrocarbon tether and a sp(2) ester tether, the oxidation took place exclusively at the delta C-H bonds. Finally, by introducing proper tethers, regioselective hydroxylation of steroid ketones 12-14 have been achieved at the C-17, C-16, C-3, and C-5 positions.

1,n‐Hydrogen‐Atom Transfer (HAT) Reactions in Which n≠5: An Updated Inventory

“…[59] The regioselective 1,6hydrogen-atom abstraction This reaction should be connected to the regioselective oxidation of unactivated CÀH bonds by dioxiranes, for which a concerted mechanism was preferred. [60] In order to reach satisfying yields, it is mandatory to restrict the flexibility of the tether, which can be done by playing with the Thorpe-Ingold effect (R = Me, 77 % and R = H, 13 % only). It must be noted that no selectivity was registered in the transfer of secondary hydrogen atoms from the aliphatic tether in 25.6 (Scheme 25 B).…”

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

“…A shorter tether length forces oxidation at C15, while a longer tether allows the benzophenone oxidant to reach C17–H. 192–194 …”

Three‐Membered Heterocycles. Structure and Reactivity

“…In this intramolecular manifestation, geometric factors override electronic preferences. Thus, the dioxirane generated from ketone 856 also engages the secondary d-position over the adjacent tertiary position, ultimately forming the bicyclic hemiacetal 857 [823].…”