Photocatalyzed Intermolecular Aminodifluoromethylphosphonation of Alkenes: Facile Synthesis of α,α‐Difluoro‐γ‐aminophosphonates

Abstract

An efficient and practical method for the synthesis of α,α-difluoro-γ-aminophosphonates through photocatalyzed intermolecular aminodifluoromethylphosphonation of alkenes has been developed. In this reaction, difluoromethylphosphonate is used as an important fluorinated reagent. Furthermore, the mild reaction conditions, simple operation, and broad substrate scope make this protocol very practical and attractive. The derivatization reaction in the synthesis of difluoromethylphosphonated chiral binaphthylamine ligands and α,α-difluoro-γ-aminophosphoric acid highlight the applicability of this method.

Intermolecular radical carboamination of alkenes

“…80 The Jiao group reported three-component radical azidoperfluoroalkylation of alkenes (104), in which the perfluoroalkyl radicals are generated from the corresponding iodides which can be reduced by a Ru(I)-complex. 81 Several examples on three-component aminodifluoroalkylation of alkenes were presented by using a-bromo-a,a 0 -difluoro-amides, 82 -esters 83 and -phosphonates 84 as difluoroalkyl radical precursors, yielding the corresponding alkene aminodifluoroalkylation products 105-107 under mild conditions in good to excellent yields. Li and co-workers reported a silver mediated radical carboamination of alkenes with alkyl nitriles and amines to prepare diverse g-amino alkyl nitriles 108 (Scheme 26).…”

Photocatalytic Difluoromethylation Reactions of Aromatic Compounds and Aliphatic Multiple C–C Bonds

“…Q. Yang, S.-D. Yang, and collaborators [71] have disclosed an efficient and practical method for the synthesis of α,α-difluoro-γ-aminophosphonates through photocatalyzed intermolecular aminodifluoromethylphosphonation of alkenes utilizing BrCF2P(O)(OR)2 as the difluoromethylating First, a thiyl radical RS • generated from methyl 2-mercaptoacetate HSAcOMe abstracts a hydrogen atom from the Hantszch ester Et-HE, giving rise to a thiol and Et-HE radical A. Radical A is sufficiently reductive (E 1/2 red < −1.15 V vs. SCE) to transfer a single electron to the excited-state of Ir* (E 1/2 Ir III * /II = 0.31 V vs. SCE), which results in the formation of a pyridine compound B and fac-Ir II (ppy) 3 .…”

“…Q. Yang, S.-D. Yang, and collaborators [71] have disclosed an efficient and practical method for the synthesis of α,α-difluoro-γ-aminophosphonates through photocatalyzed intermolecular aminodifluoromethylphosphonation of alkenes utilizing BrCF 2 P(O)(OR) 2 as the difluoromethylating reagent. The authors optimized the reaction conditions employing 1,1-diphenylethene (0.2 mmol), BrCF 2 P(O)(OEt) 2 (0.4 mmol), p-amino-anisol (0.28 mmol), fac-[Ir(ppy) 3 ] (1 mol%), NaI (10 mol %), Cs 2 CO 3 (0.3 mmol) in CH 2 Cl 2 as the solvent, for 24 h under blue LED irradiation.…”

“…Q The authors in [71] also investigated the substrate scope with regard to the amine, employing different nitrogen bases, affording good results of the aminodifluoromethylphosphonation products derived from 1,1-diphenylethene. The authors in [71] also investigated the substrate scope with regard to the amine, employing different nitrogen bases, affording good results of the aminodifluoromethylphosphonation products derived from 1,1-diphenylethene.…”

“…The authors in [71] proposed a reaction mechanism such as that shown in Scheme 20. First, the photocatalyst fac-[Ir(ppy) 3 ] is excited by visible light irradiation (blue LEDs) to generate the excited Ir 3+* , which could undergo an ET process with the difluorine reagent BrCF 2 P(O)(OiPr) 2 A to form the difluoromethylphosphonation radical B and Ir 4+ .…”