Copper-Catalyzed Radical N-Demethylation of Amides Using N-Fluorobenzenesulfonimide as an Oxidant

Abstract

An unprecedented N-demethylation of N-methyl amides has been developed by use of N-fluorobenzenesulfonimide as an oxidant with the aid of a copper catalyst. The conversion of amides to carbinolamines involves successive single-electron transfer, hydrogen-atom transfer, and hydrolysis, and is accompanied by formation of N-(phenylsulfonyl)benzenesulfonamide. Carbinolamines spontaneously decompose to N-demethylated amides and formaldehyde, because of their inherent instability.Letter pubs.acs.org/OrgLett

An Environmentally Benign, Catalyst‐Free N−C Bond Cleavage/Formation of Primary, Secondary, and Tertiary Unactivated Amides

“…3,3‐Dimethyl‐N‐phenylbutanamide [16c] ( 3I ): Using the experimental procedure EP‐1 , the product was obtained as light brown solid in 78 % yield; 1 H NMR (400 MHz, DMSO‐d 6 ) δ 9.77 (s, 1H), 7.59 (d, J =8 Hz, 2H), 7.27 (t, 2H), 7.01 (t, 1H), 2.18 (s, 2H), 1.02 (s, 9H); 13 C NMR (100 MHz, DMSO‐d 6 ) δ 169.96, 139.28, 128.58, 122.94, 119.18, 49.60, 30.83, 29.62.…”

Palladium-Catalyzed Desulfurative Hiyama Coupling of Thioureas to Achieve Amides via Selective C–N Bond Cleavage

“…1 H NMR (600 MHz, CDCl 3 ):  = 7.26-7.22 (m, 3 H), 7.18 (t, J = 7.5 Hz, 2 H), 7.03 (d, J = 8.1 Hz, 2 H), 6.93 (d, J = 8.1 Hz, 2 H), 3.49 (s, 3 H), 2.29 (s, 3 H). 21 Pale yellow liquid; yield: 37.1 mg (55%). 1 H NMR (600 MHz, CDCl 3 ):  = 7.33-7.29 (m, 3 H), 7.27-7.23 (m, 1 H), 7.22-7.16 (m, 3 H), 7.01-6.95 (m, 2 H), 3.50 (s, 3 H), 2.27 (s, 3 H).…”

“…1 H NMR (600 MHz, CDCl 3 ):  = 7.84 (d, J = 8.4 Hz, 2 H), 7.79 (s, 1 H), 7.65 (d, J = 7.8 Hz, 2 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.19 (t, J = 7.2 Hz, 1 H). 21 White solid; yield: 30.9 mg (42%); mp 53-55 °C. 1 H NMR (600 MHz, CDCl 3 ):  = 7.28-7.24 (m, 4 H), 7.19 (t, J = 7.8 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 2 H), 7.04 (d, J = 7.8 Hz, 2 H), 3.51 (s, 3 H).…”

Chemodivergence made possible by micellar photocatalysis: C-H arylation vs. N-dealkylation of chlorinated benzamides in aqueous media

“…This thermodynamically challenging reaction is mediated in nature by Cytochrome P450, [11][12][13] but chemical methods are scarce and very limited in scope. [14][15][16] We wondered if the reactivity of benzamide N-units could be promoted by combining the benefits of confined aqueous environment with the use of chlorine atoms as sacrificial directing groups. [17,18] We wished to achieve target reactivity through initial C-Cl activation followed by intramolecular 1,5 hydrogen-atom transfer (1,5-HAT).…”