Phosphorus(III)-Mediated, Tandem Deoxygenative Geminal Chlorofluorination of 1,2-Diketones

Abstract

Tetrasubstituted carbon containing two different halogen substituents was constructed in a single-step operation by utilizing the carbene-like reactivity of dioxaphospholene through the tandem reaction of electrophilic and nucleophilic halogenating reagents. It was crucial to devise non-dealkylatable phosphoramidite, which enabled the efficient formation of geminal chlorofluorides from various 1,2-diketones with (PhSO2)2NF and n-Bu4NCl. In addition, selective functionalization of the chlorine substituent was demonstrated, and the absence of halogen scrambling was confirmed.

α-Fluoroamine synthesis via P(iii)-mediated deoxygenative geminal fluorosulfonimidation of 1,2-diketones

“…As a result, 4m with a methyl group was obtained as a single constitutional isomer albeit in a low yield. Consistent with the previous observation, 7 the reaction took place efficiently with a cyclopropyl group to provide 4n in a much increased yield. However, the site-selectivity decreased at the same time probably because the cyclopropyl group could also activate the adjacent position.…”

“…Recently, our group has extended the synthetic utility of dioxaphospholene through the design of a neopentyl glycol-derived phosphorus( iii ) reagent 2 . 7 It was shown that the phosphoramidite moiety ensures the complete formation of dioxaphospholene, thereby leaving no phosphorus( iii ) Lewis base in the reaction mixture. Thus, the unproductive reaction between the P( iii ) reagent and the electrophile is prevented, and consequently, the scope of the electrophile is broadened.…”

P(NMe2)3-Mediated Reductive Intramolecular Annulation of Benzoylformates Tethered with a Trisubstituted Alkene Unit and Synthesis of 2,2-Disubstituted 2H-Chromenes

“…As a result, many important and metal-free organic reactions including insertion reaction of polar single bond, polar double bond involving (1 + 2) annulation, (1 + 4) annulation of electron-poor conjugate system, and others have been successfully realized (Scheme , a). Most recently, new advances in the K–R adduct chemistry were also continuously witnessed . The K–R adduct-mediated (3 + 2) annulation was developed by Wang, in which the K–R adduct of benzils acts as a three-atom synthon .…”

Direct access to α,α-chlorofluoro arylketones via mild electrophilic heterohalogenation of arylalkynes

“…7 Later, Chung et al described a synthesis of α,α-chlorofluoroketones from 1,2-diketones via dioxaphospholene-mediated formation of the dioxaphospholene intermediate followed by α,α-chlorofluorination in the presence of (PhSO 2 ) 2 NF and n-Bu 4 NCl (Scheme 1d). 8 Very recently, Shibatomi et al reported an interesting method for the synthesis of relevant compounds via amine-catalyzed decarboxylative chlorination of α-fluoro-β-oxocarboxylic acids (Scheme 1e). 9 Despite the significant utility, these synthetic protocols require either difficult accessible feedstocks or multiple-step operation.…”