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

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.

Key words

polyenes - cyclization - sulfenocyclization - kinetics - Lewis base catalysis - hexafluoroisopropyl alcohol

• References and Notes

• 1 Yoder RA, Johnston JN. Chem. Rev. 2005; 105: 4730
• 2 Ungarean CN, Southgate EH, Sarlah D. Org. Biomol. Chem. 2016; 14: 5454
• 3 Samanta RC, Yamamoto H. J. Am. Chem. Soc. 2017; 139: 1460
• 4 Cochrane NA, Nguyen H, Gagne MR. J. Am. Chem. Soc. 2013; 135: 628
• 5 Sethofer SG, Mayer T, Toste FD. J. Am. Chem. Soc. 2010; 132: 8276
• 6 Schafroth MA, Sarlah D, Krautwald S, Carreira EM. J. Am. Chem. Soc. 2012; 134: 20276
• 7 Snyder SA, Treitler DS, Schall A. Tetrahedron 2010; 66: 4796
• 8 Knowles RR, Lin S, Jacobsen EN. J. Am. Chem. Soc. 2010; 132: 5030
• 9 Rendler S, MacMillan DW. C. J. Am. Chem. Soc. 2010; 132: 5027
• 10 Fan L, Han C, Li X, Yao J, Wang Z, Yao C, Chen W, Wang T, Zhao J. Angew. Chem. Int. Ed. 2018; 57: 2115
• 11 Tao Z, Robb KA, Zhao K, Denmark SE. J. Am. Chem. Soc. 2018; 140: 3569
• 12 Denmark SE, Hartmann E, Kornfilt DJ. P, Wang H. Nat. Chem. 2014; 6: 1056
• 13 Hartmann E, Denmark SE. Helv. Chim. Acta 2017; 100: e1700158
• 14 Bartlett PA, Brauman JI, Johnson WS, Volkmann RA. J. Am. Chem. Soc. 1973; 95: 7502
• 15 Denmark SE, Kornfilt DJ. P. J. Org. Chem. 2017; 82: 3192
• 16 Kauch M, Hoppe D. Can. J. Chem. 2001; 79: 1736
• 17 Kauch M, Hoppe D. Synthesis 2006; 1578
• 18 An additional phenol 1e (R = Me) was prepared from 5e (R = Me) in an analogous fashion. Unfortunately, it was discovered that the ¹⁹F NMR resonances of 1e and product 2e overlapped when HFIP was used as the reaction solvent. As a result, rate data could not be obtained for this substrate by using this experimental setup.
• 19 Rohbogner CJ, Clososki GC, Knochel P. Angew. Chem. Int. Ed. 2008; 47: 1503
• 20 Lin W, Baron O, Knochel P. Org. Lett. 2006; 8: 5673
• 21 Burés J. Angew. Chem. Int. Ed. 2016; 55: 2028
• 22 Burés J. Angew. Chem. Int. Ed. 2016; 55: 16084
• 23 Nielsen CD.-T, Burés J. Chem. Sci. 2019; 10: 348
• 24 An additional homogeranylarene substrate 12b (see Supplementary Information) was prepared, but did not convert cleanly into 13b under the standard reaction conditions, indicating that the arene of 12b is a poor nucleophile compared with 12a. This disparity is rationalized by the large difference between the σ_meta (+0.12) and σ_para (–0.27) Hammett constants for the methoxy group.
• 25 In addition to nucleophilic ring-opening reactions at carbon, thiiranium ions are also susceptible to nucleophilic attack at sulfur. The relative rates of these reactions are dependent on the substitution patterns of the thiiranium ion; see: Lucchini V, Modena G, Pasi M, Pasquato L. J. Org. Chem. 1997; 62: 7018 ; It is noted that differences in reactivity probably exist between thiiranium ions resulting from the trisubstituted alkene 1 (or 12) and the disubstituted alkene 14, although it is unclear how these differences would impact the overall mechanistic picture
• 26 Hexahydroxanthenes 2a–d; 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.