Chemoselective Synthesis of N‐arylbenzamides and Benzoyloxyacetanilides from Aryl Isocyanides: Styrene as Aryl and Arylcarboxymethylene Source

Abstract

Styrenes serve as unique aryl or arylcarboxymethylene source towards aryl isocyanides in the presence of Cu(II)/TBHP, and yield N-arylbenzamides or benzoyloxyacetanilides respectively. The chemoselectivity of the reaction is controlled by the nature of the substituents present on styrene ring. Whereas styrenes substituted with electronreleasing alkyl and alkoxy groups yield N-arylbenzamides, unsubstituted styrene and those with electron-withdrawing substituents furnish benzoyloxyacetanilides as the major product. With benzylamines as the substrate, N-arylbenzamides are formed exclusively as they act only as an aryl donor. TBHP serves as a promoter and oxygen source. Both the pathways are believed to proceed through an initial oxidative CÀC bond cleavage of styrene.

Styryl Group, a Friend or Foe in Medicinal Chemistry

“…[28] Styrene also serves as an aryl or arylcarboxymethylene surrogate in the presence of Cu/TBHP. [29] Because of the vinylic hyperconjugation, it also undergoes ortho-para nucleophilic aromatic substitution. However, alkene typically reacts preferentially over the ring.…”

“…Though styrene is a hydrocarbon, it is considered a functional group as its olefin can undergo deprotonation to form benzylic cation or benzylic radical [28] . Styrene also serves as an aryl or arylcarboxymethylene surrogate in the presence of Cu/TBHP [29] . Because of the vinylic hyperconjugation, it also undergoes ortho‐para nucleophilic aromatic substitution.…”

Transition Metal and Inner Transition Metal Catalyzed Amide Derivatives Formation through Isocyanide Chemistry

“…In this context, styrenes substituted with electronreleasing alkyl and alkoxy groups and also benzylamines acted as aryl sources and react with aryl isocyanides to form N-arylbenzamides. 20 The reaction was catalyzed by Cu(OAc) 2 in the presence of tert-butyl hydroperoxide (TBHP). A Cu-catalyzed cross-coupling reaction of arenediazonium salts and isocyanides gave arenecarboxamides in moderate to good yields.…”

“…The reaction of styrenes and aryl isocyanides utilizing Cu(OAc) 2 and TBHP has a unique chemoselectivity giving benzoyloxyacetanilides 80 (Scheme 28). 20 A surprising point is that unsubstituted styrene and those with electronwithdrawing substituents act as an arylcarboxymethylene surrogate and give benzoyloxyacetanilides 80, while styrenes substituted with electron-releasing alkyl and alkoxy groups yield N-arylbenzamides (Section 2). Mechanistically, it was shown that the reaction proceeds by a radical…”

Direct Amidation of Carboxylic Acids with Nitroarenes

“…4-(tert-Butyl)-N-(4-chlorophenyl)benzamide (3j). 36 Following the general procedure A, the title compound was prepared using 4-(tertbutyl)benzoic acid (1.2 equiv., 0.60 mmol, 106.9 mg) and 1-chloro-4nitrobenzene (1.0 equiv., 0.50 mmol, 78.8 mg) using petroleum ether/EtOAc (20:1) as an eluent to give the title compound as a white amorphous solid (79.9 mg, 56%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.86−7.75 (m, 3H), 7.60 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 7.7 Hz, 2H), 7.33 (d, J = 7.9 Hz, 2H), 1.35 (s, 9H).…”