Synlett 2021; 32(04): 401-405
DOI: 10.1055/s-0040-1705968
cluster
Radicals – by Young Chinese Organic Chemists

Radical-Mediated Hetaryl Functionalization of Nonactivated Alkenes through Distal ipso-Migration of O- or S-Hetaryls

Huihui Zhang
a  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, P. R. of China   Email: [email protected]
,
Meishan Ji
a  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, P. R. of China   Email: [email protected]
,
Youhao Wei
a  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, P. R. of China   Email: [email protected]
,
Haodong Chen
a  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, P. R. of China   Email: [email protected]
,
Xinxin Wu
a  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, P. R. of China   Email: [email protected]
,
Chen Zhu
a  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, P. R. of China   Email: [email protected]
b  Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
› Author Affiliations
C.Z. is grateful for the financial support from the National Natural Science Foundation of China (21722205, 21971173) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).


Dedicated to Ilhyong Ryu on the occasion of his 70th birthday

Abstract

A radical-mediated hetaryl functionalization of nonactivated alkenes through distal ipso-migration of O- or S-containing hetaryls was developed. Furyl, benzofuryl, thienyl, and benzothienyl groups showed satisfactory migratory abilities. A variety of heteroatom-centered radicals, including azido, trifluoromethylsulfanyl, and silyl radicals readily trigger the migration cascade, and a new C–heteroatom and C–C bond are concomitantly constructed in the reaction. This method provides an efficient approach to the synthesis of high-valued complex O- or S-hetaryl compounds.

Supporting Information



Publication History

Received: 15 August 2020

Accepted after revision: 21 September 2020

Publication Date:
30 October 2020 (online)

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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  • 14 4-(1-Benzofuran-2-yl)-1-phenyl-5-[(trifluoromethyl)sulfanyl]pentan-1-one (3a); Typical Procedure Tertiary alcohol 1a (0.2 mmol, 1.0 equiv), AgSCF3 (0.3mmol, 1.5 equiv), and Na2S2O8 (0.6 mmol, 3.0 equiv) were loaded into a flame-dried reaction vial that was subjected to three cycles of evacuation and flushing with N2. DMF (2.0 mL) was added to the mixture from a syringe, and the mixture was stirred at 25 °C until the starting material was consumed (TLC). The mixture was then extracted with EtOAc (3 × 10 mL), and the combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by flash column chromatography [silica gel, EtOAc–PE (30:1)] to give a white solid; yield: 78.7 mg (87%); mp 93–94 °C. FTIR: 3676, 2988, 2970, 1792, 1671, 1636, 1522, 1436, 1374 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.91–7.81 (m, 2 H), 7.57–7.49 (m, 2 H), 7.47–7.37 (m, 3 H), 7.29–7.20 (m, 2 H), 6.55 (d, J = 0.8 Hz, 1 H), 3.38–3.26 (m, 3 H), 2.98 (t, J = 7.2 Hz, 2 H), 2.42–2.33 (m, 1 H), 2.27–2.17 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 198.9, 157.0, 154.9, 136.6, 133.2, 131.0 (q, J C–F = 304.3 Hz), 128.6, 128.1, 128.0, 124.1, 122.9, 120.8, 111.1, 104.8, 39.3, 35.8, 33.7 (q, J C–F = 1.9 Hz), 27.1. 19F NMR (376 MHz, CDCl3): δ = –41.2 (s). HRMS (ESI): m/z [M + Na]+ calcd for C20H17F3NaO2S; 401.0794; found: 401.0793.

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  • 17 4-(1-Benzofuran-2-yl)-1-phenyl-5-(triphenylsilyl)pentan-1-one (4a); Typical Procedure Tertiary alcohol 1a (0.2 mmol, 1.0 equiv), Ph3SiH (1.0 mmol, 5.0 equiv), tert-butyl peroxyacetate (0.8 mmol, 4.0 equiv, 50 wt.% in mineral spirit), CuO (0.02 mmol, 10 mol%), and DMAP (0.05 mmol, 0.25 equiv) were loaded into a sealed tube which was subjected to three cycles of evacuation and flushing with N2. Benzene (2 mL) was added to the mixture, the tube was sealed, and the mixture was stirred at 130 °C until the starting material was consumed (TLC). The organic solvent was removed under vacuum, and the residue was purified by flash column chromatography [silica gel, EtOAc–PE (30:1)] to give a colorless oil; yield: 62.5 mg (59%). FTIR: 3068, 3011, 2922, 1772, 1684, 1455, 1428, 1363, 1253, 1219 m–1. 1H NMR (400 MHz, CDCl3): δ = 7.80–7.72 (m, 2 H), 7.51–7.45 (m, 7 H), 7.38–7.34 (m, 2 H), 7.34–7.28 (m, 5 H), 7.26–7.22 (m, 6 H), 7.19–7.10 (m, 2 H), 6.10 (s, 1 H), 3.28–3.16 (m, 1 H), 2.84–2.70 (m, 2 H), 2.25–2.05 (m, 3 H), 1.91–1.83 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 199.7, 160.9, 154.4, 136.9, 135.6, 134.6, 132.9, 129.4, 128.5, 128.5, 128.0, 127.8, 123.1, 122.3, 120.3, 110.9, 103.0, 36.4, 34.9, 32.1, 19.4. HRMS (ESI): m/z [M + Na]+ calcd for C37H32NaO2Si: 559.2064; found: 559.2068.
  • 18 Detailed mechanistic pathways for each reaction are presented in the Supporting Information (Figures S1–S3).
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