Carbonylation of Csp³−H Bonds through Oxidative Wittig‐Type Reaction: An Unprecedented Version of Wittig Reaction

Abstract

AW ittig-typer eaction was achieved by radical cation salt induced aerobic oxidation of Csp 3 ÀHb onds. Different from the "standard" version of the Wittig reaction, in which ac arbon-carbon double bond is formed from ac arbonyl, carbonyl groups can be installed by similar process.First reported in 1953, [1] the Wittig olefination reactioni so ne of the most powerful synthetic tools for selectivec onstruction of carbon-carbon doubleb onds.[2] Duet ot he broad applications of this method, the development of novel transformations which utilize new classes of Wittig reagents has attracted much attention in organic synthesis. [3,4] In these elegant modificationsa nd improvements, only two versions of Wittig-type reactions were fully investigated:t he classic Wittig reaction, which can installc arbon-carbon double bonds from aldehydes or ketones (Scheme 1, eq. (a)), and the aza-Wittig reaction (Staudinger reaction), which can construct carbon-nitrogen double bonds from phosphazenes (Scheme 1, eq. (b)), nitrogen based phosphorus ylides. The formation of the four-membered oxaphosphetane intermediate (Scheme 1, intermediate I) is the key step from which the product alkene or Schiff base are released accompanied by the triphenylphosphine oxide byproduct. However,t he separation of the product alkene from the byproduct triphenylphosphine oxide is ac lassical problem and typicallyr equirest edious chromatography or recrystallization. To overcome this problem,t he Horner-Wadsworth-Emmons olefination wasd eveloped, [5] in which the byproduct dialkyl phosphates are water-soluble and more easily separablef rom the alkene products than triphenylphosphine oxide.Recently,C ÀHa ctivation mediated by radical intermediates has attracted considerable attention, and av ariety of methods have been established.[6] As part of our ongoing research project on radical cation initiatedC ÀHb ond functionalization, [7] we are particularly interested in developing an ew process for these phosphorus substrates. We hypothesizedt hat oxidizing Csp 3 ÀHb onds alpha to phosphorus could produce af ree radical that could be captured by dioxygenr esulting in the formation of an oxo-four-membered intermediate (Scheme 1, intermediate I, X = carbon and Y = oxygen).A fter dialkyl phosphate leaves,acarbonyl compound arising from af ormal N-formylation would be afforded (Scheme1,e q. (c)). If feasible, this transformation would be an interesting variant of Wittig reaction, where insteado ff orming olefins from carbonyls, carbonyl groups could be installed throughW ittig-type process.We chose a-anilino phosphonate 1a,w hich can be easily synthesized from the corresponding aniline, formaldehyde and trimethyl phosphite (see the supporting information), as the model substrate to test the possibility of this oxidative Wittig reaction. Our study began with oxidation of 1a initiated by TBPA + · (tris(4-bromophenyl)aminium hexachloroantimonate) in the presence of dioxygen (Table 1). To our delight, the carbonylation occurred smoothly in the presence of 10 ...

Multifunctionalization of C(sp3)−H Bond of Tetrahydroisoquinolines through C−H Activation Relay (CHAR) Using α‐Cyanotetrahydroisoquinolines as Starting Materials

“…In this reaction, the introduction of the electron‐withdrawing group, phosphate group, is crucial to increase the activity of the sp 3 C−H bond adjacent to nitrogen and stabilize the generated radical intermediate by captodative effect [7] to be captured by oxygen. However, due to the existence of the phosphate group, the oxidative Wittig reaction was inevitable, which blocked the intramolecular HAT and disturbed the desired reaction process [5b,8] . So we wondered whether other electron‐withdrawing groups could be installed on the 1‐position to avoid undesired side reactions while activating the substrate.…”