Synlett 2019; 30(14): 1656-1661
DOI: 10.1055/s-0039-1690111
cluster
© Georg Thieme Verlag Stuttgart · New York

Unusual Kinetic Profiles for Lewis Base-Catalyzed Sulfenocyclization of ortho-Geranylphenols in Hexafluoroisopropyl Alcohol

,
Soumitra V. Athavale
,
We are grateful to the National Institutes of Health (GM R35 127010) for generous financial support.
Further Information

Publication History

Received: 11 May 2019

Accepted after revision: 17 June 2019

Publication Date:
08 July 2019 (online)


Published as part of the Cluster Organosulfur and Organoselenium Compounds in Catalysis

Abstract

The kinetic behavior of the Lewis base-catalyzed sulfenocyclization of polyenes in hexafluoroisopropyl alcohol (HFIP) was explored. The rate of reaction is not dependent on the electronic properties of the terminal nucleophile, suggesting that this capture step is not rate limiting. Additionally, fractional orders were observed for two of the reaction components. This intriguing profile appears unique to the polyene sulfenocyclization reaction and is not merely due to solvent effects.

Supporting Information

 
  • References and Notes

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  • 26 Hexahydroxanthenes 2ad; General Procedure A 50-mL round-bottomed flask equipped with a stirrer bar was charged with sulfenylating agent 3 (1.01 mmol, 1.01 equiv), HFIP (10 mL), and substrate 1 (1.0 mmol). Catalyst (S)-4 (0.01 mmol, 0.01 equiv) was added and the mixture was stirred at 25 °C for 12 h. Some white precipitates and/or a color change were typically observed at longer reaction times. Upon completion of the reaction [TLC; hexanes–CH2Cl2 (80:20)], the mixture was diluted with CH2Cl2 (5 mL) and volatile components were removed by rotary evaporation (30 °C, 15 mm Hg). The crude product was purified by chromatography [silica gel, hexanes–CH2Cl2 (gradient elution)] to give a white solid. The product was triturated in boiling MeOH or EtOH (~1.5 mL) and the mother liquor was decanted to afford 2 in >99% purity (quantitative 1H NMR analysis). (2R,4aR,9aR)-2-[(2,6-Diisopropylphenyl)thio]-5-fluoro-7-methoxy-1,1,4a-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-xanthene (2a) White solid; yield: 355.5 mg (75%); 1H NMR (500 MHz, CDCl3): δ = 7.33 (t, J = 7.7 Hz, 1 H), 7.18 [d, J = 7.7 Hz, 2 H, HC(19)], 6.52 [dd, J = 12.3, 2.7 Hz, 1 H, HC(11)], 6.41 [br s, 1 H, HC(9)], 3.96 (hept, J = 6.7 Hz, 2 H), 3.73 (s, 3 H), 2.77 (dd, J = 16.7, 5.3 Hz, 1 H), 2.75–2.70 (m, 1 H), 2.69 (dd, J = 12.1, 3.9 Hz, 1 H), 1.97 (dt, J = 12.7, 2.9 Hz, 1 H), 1.76 (dd, J = 12.6, 5.3 Hz, 1 H), 1.74–1.64 (m, 1 H), 1.61 (dq, J = 14.0, 3.7 Hz, 1 H), 1.48 (td, J = 13.3, 3.6 Hz, 1 H), 1.41 (s, 3 H), 1.26 (d, J = 6.8 Hz, 6 H), 1.23 (s, 3 H), 1.20 (d, J = 6.9 Hz, 6 H), 1.08 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 154.1, 152.5 (d, J C–F = 10.0 Hz), 152.0 (d, J C–F = 244.4 Hz), 135.3 (d, J C–F = 11.4 Hz), 130.3, 129.2, 124.9 (d, J C–F = 3.2 Hz), 123.9, 109.0 (d, J C–F = 3.0 Hz), 101.3 (d, J C–F = 21.8 Hz), 77.0, 60.9, 55.9, 49.6, 39.9, 38.7, 31.5, 28.9, 26.7, 25.0, 24.1, 23.9 (d, J C–F = 2.7 Hz), 19.7, 16.6.