Synlett 2023; 34(20): 2465-2470
DOI: 10.1055/a-2102-7866
cluster
Special Issue Dedicated to Prof. Hisashi Yamamoto

Organocatalyzed Regioselective α,γ-Difunctionalization of Deconjugated Butenolides: Synthesis of Butyrolactone–Butyrolactam Hybrid Molecules

Swati Lekha Mondal
,
Koushik Patra
,
Rahul Yadav
,
Mahiuddin Baidya
We gratefully acknowledge financial support from Science and Engineering Research Board (SERB), India (EMR/2014/000225) and Indian Institute of Technology Madras (IIT) Madras (IOE project). S.L.M. acknowledges a fellowship from the Council of Scientific and Industrial Research, India and K.P. acknowledges a Prime Minister’s Research Fellows (PMRF) fellowship.


On the occasion of Prof. H. Yamamoto’s 80th birthday

Abstract

A highly regioselective α,γ-difunctionalization of deconjugated butenolides that allows access to hybrid molecular frameworks composed of unsaturated butyrolactone and butyrolactam motifs is reported. The reaction is catalyzed by inexpensive quinidine, and products are isolated in high yields as a single diastereomer. The γ-selective monofunctionalization was also accomplished through substrate modification.

Supporting Information



Publikationsverlauf

Eingereicht: 25. April 2023

Angenommen nach Revision: 30. Mai 2023

Accepted Manuscript online:
30. Mai 2023

Artikel online veröffentlicht:
14. Juli 2023

© 2023. Thieme. All rights reserved

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  • 9 Typical Procedures: α,γ-Difunctionalization of Deconjugated Butyrolactone: A 16×100 mm oven-dried reaction tube equipped with a magnetic stir was charged with α-amide enone 1a (110.8 mg, 2.0 equiv, 0.40 mmol), deconjugated butyrolactone 2a (34.0 mg, 1.0 equiv, 0.20 mmol), and quinidine (13 mg, 20 mol%). The reaction tube was capped with a rubber septum, evacuated, and backfilled with nitrogen gas. Anhydrous toluene (4 mL) was then added via syringe, and the reaction mixture was stirred for 36 h at room temperature. After completion of the reaction (TLC monitored), the reaction mixture was filtered and residue was subsequently washed with toluene to give pure product 3a (0.15 mmol, 79%, 109 mg) as white solid; mp 124–126 °C. 1H NMR (400 MHz, CDCl3): δ = 8.88 (s, 1 H), 8.12 (s, 1 H), 7.38–7.32 (m, 6 H), 7.28–7.24 (m, 4 H), 7.19 (br s, 3 H), 7.07–7.01 (m, 5 H), 6.85 (br s, 2 H), 5.67 (s, 1 H), 5.03 (s, 1 H), 4.68–4.54 (m, 4 H), 4.31–4.23 (m, 3 H), 3.91 (d, J = 18.6 Hz, 1 H), 3.50–3.38 (m, 2 H), 1.74 (s, 3 H), 1.31 (t, J = 6.8 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 171.0, 167.2, 167.0, 161.7, 153.1, 145.1, 144.3, 138.4, 136.9, 136.8, 136.62, 136.56, 129.0, 128.9, 128.8, 128.7 (2×C), 128.2, 128.0, 127.90 (2×C), 127.87, 127.5, 127.1, 118.3, 117.5, 90.2, 62.4, 49.4, 48.7, 47.9, 47.0, 46.95, 37.3, 23.5, 14.0. HRMS (ESI/TOF-Q): m/z [M + Na]+ calcd for C44H40N2O8Na+: 747.2677; found: 747.2695. γ-Functionalization of Deconjugated Butyrolactone: A 16×100 mm oven-dried reaction tube equipped with a magnetic stir was charged with α-amide enone 1a (66.5 mg, 1.2 equiv, 0.24 mmol), deconjugated butyrolactone 4a (20 mg, 1.0 equiv, 0.20 mmol), and quinidine (13 mg, 20 mol%). The reaction tube was capped with a rubber septum, evacuated, and backfilled with nitrogen gas. Anhydrous toluene (2 mL) was then added via syringe and the reaction mixture was stirred for 24 h at room temperature. After completion of the reaction (TLC monitored), volatiles were removed under reduced pressure and the crude product was purified by column chromatography (25% ethyl acetate/hexane) to provide pure product 5a (0.15 mmol, 80%, 60 mg) as a white solid; mp 158–160 °C. 1H NMR (400 MHz, CDCl3): δ = 7.35–7.29 (m, 4 H), 7.23–7.20 (m, 5 H), 7.16–7.14 (m, 2 H), 5.71 (d, J = 5.6 Hz, 1 H), 4.69–4.59 (q, 2 H), 4.40 (s, 1 H), 4.20 (d, J = 18.7 Hz, 1 H), 3.86 (d, J = 18.6 Hz, 1 H), 1.52 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 172.6, 167.2, 160.4, 144.4, 137.0, 136.4, 129.1 (d, J = 5.8 Hz), 129.0, 128.5, 128.0, 127.8, 121.0, 118.9, 90.5, 49.32, 49.25, 47.1, 23.7. HRMS (TOF MS ES+): m/z [M + Na]+ calcd for C23H21NO4 + Na+: 398.1363; found: 398.1365.