Iodine(III) promotes cross-dehydrogenative coupling of N-hydroxyphthalimide and unactivated C(sp3)–H bonds

Abstract

Cross-dehydrogenative coupling reactions provide a method to construct new chemical bonds by direct C–H activation without any pre-functionalization. Compared to functionalization of a C–H bond α- to ether oxygen, α- to carbonyl, or at a benzylic position, functionalization of unactivated hydrocarbons is difficult and often requires high temperatures, a transition-metal catalyst, or a superstoichiometric quantity of volatile, toxic, and explosive tert-butylhydroperoxide. Here, a cross-dehydrogenative C–O coupling reaction of N-hydroxyphthalimide with unactivated alkanes, nitriles, ethers, and thioethers has been realized by using iodobenzene diacetate as the radical initiator. The current protocol enables efficient functionalization of unactivated hydrocarbons and nitriles through inert C(sp3)–H bond activation under mild reaction conditions. O-substituted NHPI derivatives are generated in good yields under metal-free conditions.

Organic Synthesis Using Nitroxides

“…For adamantane, the intermediately generated adamantyl radical can be further oxidized to the tertiary cation that can be trapped by a nucleophile . Recently, a quite efficient oxidation approach of (un)­activated alkanes was reported using NHPI together with PIDA to generate alkyl radicals, which are subsequently trapped by PINO …”

“…1052 Recently, a quite efficient oxidation approach of (un)activated alkanes was reported using NHPI together with PIDA to generate alkyl radicals, which are subsequently trapped by PINO. 1053 An intriguing strategy to overcome the selectivity regioselectivity problem in the alkane oxidation was introduced by the groups of Osaki and Kanai. They installed an NHPIderived protecting group on an alcohol, and by generating an amidoxyl radical, they were able to perform a remote functionalization via an intramolecular HAT.…”

Efficient Photolytic Halogenation and Oxidation of Unactivated Alkyl sp3 C—H Bonds with Iodine(III)

“…[ 12 ] Compared with the other methods ( e.g ., ligand exchange, thermal decomposition or single‐electron transfer approach), photolysis can induce the generation of odanyl radical from hypervalent iodine(III) reagents under milder conditions. [6f] Therefore, based on our previous work on iodine(III), [ 13 ] we assumed that if iodanyl radical with the activity high enough to activate inert C—H bond could be generated from DIB under photolysis, halogenation and oxidation of the inert C—H bonds would be realized under mild conditions.…”

Efficient Photolytic Halogenation and Oxidation of Unactivated Alkyl sp3 C−H Bonds with Iodine (III)

“…Functionalization of Alkyl sp 3 C-H Bonds single-electron transfer approach) photolysis can induce the generation of iodanyl radical from hypervalent iodine (III) reagents under milder conditions. [5f] Therefore, based on our previous work on iodine (III), [12] we assumed that if iodanyl radical with the activity high enough to activate inert C-H bond could be generated from DIB under photolysis, then halogenation, and oxidation of the inert C-H bonds would be realized under mild conditions.…”