Photoinduced Site-Selective C(sp³)–H Chlorination of Aliphatic Amides

Abstract

Herein, we report a new photochemical method for C­(sp3)–H chlorination of amides which employs tert-butyl hypochlorite as the chlorinating agent and a household compact fluorescent lamp as the light source. The reaction proceeds via N-heterocyclic carbene SIPr·HCl-promoted N–H chlorination and subsequent photoinduced Hofmann–Löffler–Freytag chlorine atom transfer. The latter process is facilitated by (diacetoxyiodo)­benzene. This protocol exhibits a broad scope and is suitable for site-selective chlorination of methyl hydrogen as well as methylene and methine hydrogen.

Applications of Phenyliodine(III)diacetate in C−H Functionalization and Hetero‐Hetero Bond Formations: A Septennial Update

“…It was disclosed by the research groups of Zhang and Wang, how to synthesize α-bromo/iodo/chloroketones from olefins using visible light irradiation. [149] The reactions of styrenes (196) and triiodomethane underwent the transformation smoothly in the presence of PIDA as a promoter and under ambient conditions to produce the corresponding α-iodoketones (197) in good yields under sunlight irradiation without the need for additional photocatalyst (Scheme 69). Using Ru(bpy) 3 Cl 2 as a photocatalyst and blue LED (450-455 nm) ChemistrySelect illumination, the reactions of styrenes with tribromomethane and trichloromethane produced the requiredα-bromo and αchloroketones in high yields.…”

“…It was disclosed by the research groups of Zhang and Wang, how to synthesize α‐bromo/iodo/chloroketones from olefins using visible light irradiation [149] . The reactions of styrenes ( 196 ) and triiodomethane underwent the transformation smoothly in the presence of PIDA as a promoter and under ambient conditions to produce the corresponding α‐iodoketones ( 197 ) in good yields under sunlight irradiation without the need for additional photocatalyst (Scheme 69).…”

A Site-Selective C(sp3)-H Chlorination Boosted by an Imidazolium-Functionalized Cage in Water

“…This yield was nearly 2-fold higher than those obtained with B, a mixed IPr•HCl/ PhI(OAc) 2 and SIPr•HCl/PhI(OAc) 2 in water (entry 5 versus entries 6, 11, and 12). 7 The parent IPr•HCl, the blank, Cu 4 clusters, and the mixed IPr•HCl and Cu 4 clusters gave 5aa in very low yields (5%−16%) because unconverted 4aa was observed as the major product (entry 5 versus entries 7−10). It was notable that the yield in the presence of IPr•HCl had an obvious enhancement when the reaction temperature was up to 50 °C, while those of the blank and Cu 4 clusters had no significant changes (entries 7 and 10 versus 8 and 9 in parentheses).…”

δ-C–H Halogenation Reactions Enabled by a Nitrogen-Centered Radical Precursor

“…We were also curious to see whether our new hydrazonyl carboxylic acid was competent in remote C–H chlorination. Therefore, a variety of bases, photocatalysts, and solvents were explored (see the Supporting Information), ultimately allowing us to accomplish the remote C–H chlorination of 1a in 50% isolated yield using ethyl trichloroacetate (ETCA) as the chlorinating reagent. , While several examples of remote chlorination are known for sulfonamides, ranging from classic HLF conditions to more modern photochemical methods, these methods all require the intermediacy of nitrogen–chlorine bonds, either preformed , or generated in situ. , In contrast, our method circumvents the need to generate nitrogen–chlorine bonds and thus may find use in scenarios where the generation or intermediacy of nitrogen–chlorine bonds is undesirable. Indeed, given the synthetic versatility of organochlorine compounds and the presence of organochlorine motifs among several thousand natural products, new technologies and approaches for aliphatic C–H chlorination will undoubtedly remain relevant in streamlining the synthesis of such compounds.…”

“…29,46 While several examples of remote chlorination are known for sulfonamides, ranging from classic HLF conditions 47 to more modern photochemical methods, these methods all require the intermediacy of nitrogen− chlorine bonds, either preformed 48,49 or generated in situ. 50,51 In contrast, our method circumvents the need to generate nitrogen−chlorine bonds and thus may find use in scenarios where the generation or intermediacy of nitrogen−chlorine bonds is undesirable. Indeed, given the synthetic versatility of organochlorine compounds and the presence of organochlorine motifs among several thousand natural products, 52 new technologies and approaches for aliphatic C−H chlorination will undoubtedly remain relevant in streamlining the synthesis of such compounds.…”