Metal-Free Synthesis of Dibenzoxazepinones via a One-Pot SNAr and Smiles Rearrangement Process: Orthogonality with Copper-Catalyzed Cyclizations

Timothy E. Hurst; Matthew O. Kitching; Lívia C. R. M. da Frota; Keller G. Guimarães; Michael E. Dalziel; Victor Snieckus

doi:10.1055/s-0034-1378839

Synlett, Table of Contents

Synlett 2015; 26(11): 1455-1460
DOI: 10.1055/s-0034-1378839

letter

Metal-Free Synthesis of Dibenzoxazepinones via a One-Pot S_NAr and Smiles Rearrangement Process: Orthogonality with Copper-Catalyzed Cyclizations

Timothy E. Hurst

^aDepartment of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada Email: Victor.Snieckus@chem.queensu.ca

,

Matthew O. Kitching

^aDepartment of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada Email: Victor.Snieckus@chem.queensu.ca

,

Lívia C. R. M. da Frota

^aDepartment of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada Email: Victor.Snieckus@chem.queensu.ca

^bInstituto de Pesquisa de Produtos Naturais, Universidade Federal Do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H-Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil

,

Keller G. Guimarães

^aDepartment of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada Email: Victor.Snieckus@chem.queensu.ca

^cDepartmento de Química, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 – 31270-901, Belo Horizonte, MG, Brazil

,

Michael E. Dalziel

^aDepartment of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada Email: Victor.Snieckus@chem.queensu.ca

,

Victor Snieckus*

^aDepartment of Chemistry, Queen’s University, Kingston, ON, K7L 3N6, Canada Email: Victor.Snieckus@chem.queensu.ca

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Abstract

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To Peter, with fond and vivid remembrance of the birth of Synlett and in praise of how far you have taken it.

Abstract

Reported is the transition-metal-free synthesis of substituted dibenzoxazepinones using a convergent domino S_NAr–Smiles rearrangement–S_NAr process. Substrate-scope investigations demonstrated the critical importance of ring electronic effects on the efficiency of the process. In addition, the orthogonality of this approach with transition-metal-catalyzed procedures was established.

Key words

dibenzoxazepinones - domino reaction - Smiles rearrangement - nucleophilic aromatic substitution - heterocycles

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References

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22 See Supporting Information for full experimental details and compound characterization. General Procedure – Reaction of 2-Fluorobenzamides with 2-Bromophenols A sealable tube (10 mL) was charged with the 2-fluorobenzamide (1.00 mmol), the 2-bromophenol (2.00 mmol), and K₂CO₃ (0.290 g, 2.10 mmol). NMP (3 mL) was added, and the tube was sealed. The heterogeneous reaction mixture was heated to 150 °C, 180 °C, or 220 °C for 2–4 h under microwave irradiation (Biotage Initiator Microwave operating at 400 W). After cooling to r.t., the reaction mixture was partitioned between 2 M HCl (20 mL) and EtOAc (3 × 20 mL). The combined organics were washed with 2 M NaOH (2 × 20 mL) and sat. brine (20 mL), dried over MgSO₄, subjected to filtration, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel, eluting with EtOAc–hexanes (1:19 to 1:5) to deliver the title compound. N-Ethyl 7-Chlorodibenz[b,f][1,4]oxazepin-11(10H)-one (3a) The reaction of N-ethyl 2-fluorobenzamide (1a, 0.167 g, 1.00 mmol) with 2-bromo-4-chlorophenol (2a, 0.415 g, 2.00 mmol) at 220 °C for 2 h gave 3a as a colorless solid (0.170 g, 62%); mp 124–126 °C. IR (film): 1645, 1607 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.89 (dd, J = 1.7, 7.8 Hz, 1 H), 7.48 (dt, J = 1.5, 7.8 Hz, 1 H), 7.32 (d, J = 2.3 Hz, 1 H), 7.28 (s, 1 H), 7.26 (d, J = 7.3 Hz, 1 H), 7.22–7.18 (m, 2 H), 4.17 (q, J = 7.1 Hz, 2 H), 1.40 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.7 (C), 160.1 (C), 154.9 (C), 133.6 (C), 133.3 (CH), 132.0 (CH), 130.9 (C), 126.6 (C), 125.9 (CH), 124.5 (CH), 123.7 (CH), 121.9 (CH), 119.5 (CH), 44.2 (CH₂), 13.6 (Me). LRMS (EI): m/z (%) = 273/275 (58/19) [M⁺], 238 (100), 210 (24), 195 (26), 139 (15), 105 (10), 84 (13). HRMS (EI): m/z calcd for C₁₅H₁₂ClNO₂ ⁺: 273.0557; found: 273.0563.

Supplementary Material

Supporting Information