Merging Electron Transfer with 1,2‐Metalate Rearrangement: Deoxygenative Arylation of Aromatic Amides with Arylboronic Esters

Abstract

Amides are essentially inert carboxyl derivatives in many types of chemicalt ransformations.I np articular,d eoxygenative CÀCb ond formation of amides to synthetically important amines is al ong-standing challenge for synthetic chemists due to the inertness of the resonance-stabilized amide C = Ob ond. Herein, it is disclosed that by merging electrontransfer-induced activation with 1,2-metalate rearrangement, awide range of aromatic amides react smoothly with arylboron reagents,a ffording as eries of biologically relevant diarylmethylamines as deoxygenative CÀCb ond cross-coupling products.Withits simplicity and versatility,this reaction shows great promise in the synthesis of amines from amides,w hich may open up new avenues in retrosynthetic planning and find widespread use in academia and industry.Scheme 1. Merging electron transfer with 1,2-metalate rearrangement for the deoxygenative functionalization of amides.

Deoxygenative Cross‐Coupling of Aromatic Amides with Polyfluoroarenes

“…However, under these conditions only 20 % of the desired product 3 aa was detected. It is known that the reactivity of SmI 2 in a reaction can be modulated by the use of appropriate metal salts [14, 23] . Indeed, the use of 0.1 equiv of metal additives, such as NiI 2 or Pd(PPh 3 ) 4 in the reaction led to slightly enhanced yields (Table 1, entries 2 and 3, 24 % and 40 %).…”

“…[13] Recently, our group reported a deoxygenative arylation of amides with arylboronic esters by merging electron transfer induced activation with 1,2-metalate rearrangement (Scheme 1b-iii). [14] We envisioned that one of the active intermediates, generated in the process of ET to amides, might be coupled in a subsequent reaction with an appropriate reagent, thus leading to a deoxygenative CÀ C cross-coupling product, which may be developed as an alternative method for activation and functionalization of amides.…”

“…In the early 1990s, Ogawa, Sonoda and co‐workers reported seminal studies [12] on Sm/SmI 2 ‐promoted deoxygenative self‐dimerization of amides, demonstrating the viability on the direct use of an amide as an α‐aminocarbene precursor (Scheme 1b‐ii) [13] . Recently, our group reported a deoxygenative arylation of amides with arylboronic esters by merging electron transfer induced activation with 1,2‐metalate rearrangement (Scheme 1b‐iii) [14] . We envisioned that one of the active intermediates, generated in the process of ET to amides, might be coupled in a subsequent reaction with an appropriate reagent, thus leading to a deoxygenative C−C cross‐coupling product, which may be developed as an alternative method for activation and functionalization of amides.…”

Synthesis of α-Aminosilanes by 1,2-Metalate Rearrangement Deoxygenative Silylation of Aromatic Amides

“…9 In 1992, Ogawa and Sonoda used a mixed Sm/SmI 2 system successfully to reduce amides for the first time, which provided a powerful method for preparing vic-diaminoalkenes. 10 Recently, Wang and coworkers also reported a deoxyarylation of aromatic amides with arylborates 11 and deoxygenative cross-coupling of aromatic amides with polyfluoroarenes 12 with a SmI 2 /Sm system. Tetracoordinated boron-mediated 1,2-metalate rearrangement is one of the most widely used strategies in boron chemistry for the construction of various compounds.…”

Uniting Amide Synthesis and Activation by PIII/PV–Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines

“…Amides are common targets in biological and medicinal chemistry , but are challenging substrates for chemical derivatization . As a result, a diverse synthetic toolbox of mild reagents supports amide coupling, but amide activation generally employs strongly electrophilic reagents, chiefly Tf 2 O as exemplified in the work of Charette, Movassaghi, Huang, and Maulide, , to accomplish functionalization of the typically inert amide moiety. − Notwithstanding the power of Tf 2 O-mediated amide activation, the highly electrophilic nature of this reagent necessitates sequencing of the amide preparation and functionalization operations and generally precludes the use of substrates containing Lewis basic functionalities, including amines . This lack of cross-compatibility between amide coupling and activation enforces a practice whereby these two related reactions are taken as disparate synthetic tasks performed in sequence (Figure A, top).…”