Copper‐Mediated [3+2] Annulation of 3‐N‐Hydroxyallylamines with Nitrosoarenes

Abstract

Cu-mediated annulations of N-hydroxyallylamines with nitrosoarenes proceed through unprecedented formal [3+2] cycloadditions of N-hydroxyaminoallyl radicals with nitrosoarenes. Our mechanistic analysis opposes a 5-endo-trig cyclization involved in the final ring-closure step. To manifest the reaction utility, chemical elaborations of resulting isoxazolidinyl products into 2- or 3-substituted quinoline N-oxides and acyclic 1,3-diamino-2-ols are also described.

Synthesis of Amides via the Amination of Aldehydes with Hydroxylamines Promoted by TBAF·3H2O

“…(Z)-1,2-Diphenyldiazene 1-Oxide 6. 47 Yellow solid, 68% yield (62.0 mg), mp 156−157 °C; R f 0.30 (PE/EA = 50/1); 1 H NMR (500 MHz, CDCl 3 ) δ 8.33 (d, J = 8.0 Hz, 2H), 8.18 (d, J = 7.5 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.51 (q, J = 16.5, 8.0 Hz, 4H), 7.40 (t, J = 7.5 Hz, 1H); 13 General Procedure for the Synthesis of Compounds 5a from 1a, 2a, 3a, and 4a on a Larger Scale. N-Phenylhydroxylamine 1a (11.3 mmol, 1 equiv) and benzaldehyde 2a (11.3 mmol, 1 equiv) were put in a dried round-bottom flask (100 mL) with a magnetic bar.…”

“…61 Yellow solid, 75% yield (103.4 mg), mp 182−183 °C; R f 0.45 (PE/EA = 10/1); 1 H NMR (500 MHz, CDCl 3 ) δ 7.96 (d, J = 8.0 Hz, 2H), 7.88 (s, 1H), 7.75 (d, J = 7.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 164.4, 137.9, 136.0, 133.7 (q, J C−F = 33.0 Hz), 130.1, 129.2, 127.5, 125.9 (q, J C−F = 3.8 Hz), 123.5 (q, J C−F = 273.2 Hz), 121.6; 19 (Z)-1,2-Diphenyldiazene 1-Oxide 6. 47 Yellow solid, 68% yield (62.0 mg), mp 156−157 °C; R f 0.30 (PE/EA = 50/1); 1 H NMR (500 MHz, CDCl 3 ) δ 8.33 (d, J = 8.0 Hz, 2H), 8.18 (d, J = 7.5 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.51 (q, J = 16.5, 8.0 Hz, 4H), 7.40 (t, J = 7.5 Hz, 1H); 13 General Procedure for the Synthesis of Compounds 5a from 1a, 2a, 3a, and 4a on a Larger Scale. N-Phenylhydroxylamine 1a (11.3 mmol, 1 equiv) and benzaldehyde 2a (11.3 mmol, 1 equiv) were put in a dried round-bottom flask (100 mL) with a magnetic bar.…”

Organic Synthesis Using Nitroxides

“…The proposed mechanism involves the initial formation of a nitroxyl radical 149 , which can abstract a hydrogen atom from the allylic position of 147 . The resulting allylic radical 150 then undergoes a multistep sequence, including a dimerization step, leading to the formation of the final product 148 . , In the presence of nitrosoarenes, isoxazolidines were obtained …”

“…The resulting allylic radical 150 then undergoes a multistep sequence, including a dimerization step, leading to the formation of the final product 148. 1004,1005 In the presence of nitrosoarenes, isoxazolidines were obtained. 1005 Oxoammonium salts were successfully applied in the aromatization of cyclic dienes 1006,1007 and also for allylic oxidation.…”

“…1004,1005 In the presence of nitrosoarenes, isoxazolidines were obtained. 1005 Oxoammonium salts were successfully applied in the aromatization of cyclic dienes 1006,1007 and also for allylic oxidation. 1008−1010 In allylic oxidations, even trisubstituted alkenes 151 could be converted efficiently to alkoxyamines 153 using a stoichiometric amount of Bobbitt's salt (Scheme 49a).…”