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Synlett
DOI: 10.1055/a-2294-5395
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Copper-Catalyzed [4+1] and [4+2] Reactions through Tandem ­Remote Propargylation/Cyclization/Isomerization with an Amine or a Hydrazine

Yu-Ze Sun
a   Department of Chemistry, Shanghai Normal University, Shanghai 200234, P. R. of China
b   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai, 200032, P. R. of China
c   State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai, 200032, P. R. of China
,
Guo-Qiang Lin
a   Department of Chemistry, Shanghai Normal University, Shanghai 200234, P. R. of China
b   State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai, 200032, P. R. of China
,
Zhi-Tao He  ∗
c   State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai, 200032, P. R. of China
d   School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, P. R. of China
e   Ningbo Zhongke Creation Center of New Materials, Ningbo, 315899, P. R. of China
› Author AffiliationsWe acknowledge financial support from the National Natural Science Foundation of China (22371292 and 22071262), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0610000), Natural Science Foundation of Ningbo (2023J036), Shanghai Municipal Committee of Science and Technology (22ZR1475200), the State Key Laboratory of Organometallic Chemistry, and Shanghai Institute of Organic Chemistry.
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Abstract

Two novel copper-catalyzed cyclization reactions involving a remote propargylic substitution/cyclization/isomerization cascade are disclosed. Derivatives of the seldomly studied heterocycles thieno[2,3-c]pyrrole and thieno[2,3-d]pyridazine are conveniently synthesized in moderate to good yields from primary amines or arylhydrazines through [4+1] and [4+2] reactions, respectively. Preliminary mechanistic experiments corroborated the occurrence of the designed cascade reactions.

Key words

copper catalysis - propargylic substitution - [4+1] cyclization - [4+2] cyclization - arylhydrazines - amines

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2294-5395.
  • Supporting Information


Publication History

Received: 29 February 2024

Accepted after revision: 25 March 2024

Accepted Manuscript online:
25 March 2024

Article published online:
15 April 2024

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  • 20 [4+1] Reaction with Amines; General ProcedureIn a N2-filled glovebox, a 4 mL vial was charged sequentially with Cu(MeCN)4PF6 (1.9 mg, 0.0050 mmol), ligand L1 (1.3 mg, 0.0060 mmol), the appropriate alkyne 1 (0.10 mmol), Et3N (28 μL, 0.20 mmol), the appropriate amine 2 (0.12 mmol), and anhyd MeOH (0.10 mL). The resulting mixture was stirred at 60 °C for 4 h, then diluted with hexane and filtered through Celite. The filtrate was concentrated and purified by flash column chromatography. 4-Methyl-5,6-diphenyl-5H-thieno[2,3-c]pyrrole (3a) Yellow oil; yield: 23.7 mg (82%). 1H NMR (400 MHz, CDCl3): δ = 7.45–7.39 (m, 3 H), 7.26–7.23 (m, 2 H), 7.18–7.14 (m, 2 H), 7.09–6.95 (m, 5 H), 2.33 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 139.7, 132.8, 130.9, 129.3, 128.7, 128.3, 128.1, 126.7, 124.99, 124.96, 123.7, 121.5, 120.8, 116.2, 12.5. HRMS (EI): m/z [M+] calcd for C19H15NS: 289.0920; found: 289.0926.
  • 21 [4+2] Reaction with Hydrazines; General ProcedureIn a N2-filled glovebox, a 4 mL vial was charged sequentially with Cu(MeCN)4PF6 (3.7 mg, 0.010 mmol), ligand L1 (2.6 mg, 0.012 mmol), the appropriate alkyne 1 (0.10 mmol), Et3N (28 μL, 0.20 mmol), the appropriate arylhydrazine 4 (0.20 mmol), and anhyd MeOH (0.10 mL). The resulting mixture was stirred at 60 °C for 4 h, then diluted with hexane and filtered through Celite. The filtrate was concentrated and purified by flash column chromatography. 4-Methyl-6,7-diphenyl-6,7-dihydrothieno[2,3-d]pyridazine (5a) Green oil; yield: 25.3 mg (83%). 1H NMR (400 MHz, CDCl3): δ = 7.32–7.19 (m, 9 H), 7.16 (d, J = 5.2 Hz, 1 H), 6.99 (d, J = 5.2 Hz, 1 H), 6.90–6.86 (m, 1 H), 6.57 (s, 1 H), 2.38 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 146.5, 141.2, 138.8, 136.7, 128.99, 128.97, 127.78, 127.76, 125.8, 124.0, 122.7, 120.4, 115.1, 58.7, 19.8. HRMS (EI): m/z [M+] calcd for C19H16N2S: 304.1029; found: 304.1033.