Trityl Cation Catalyzed Intramolecular Carbonyl-Ene Cyclization and [2+2] Cycloaddition

Abstract

An unprecedented metal-free catalytic system composed of trityl halides and thioureas has been found to be a convenient source for the generation of trityl cation species, and this cooperative catalytic system was proved to be highly effective for intramolecular carbonyl-ene cyclization and [2+2] cycloadditions.

Key words

trityl cation catalysis - intramolecular carbonyl-ene - intramolecular [2+2] cycloaddition - thiourea catalyst

• References and Notes


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• 22a Although further study is necessary, at present we believe that the reaction proceeds via a dipolar zwitterionic mechanism. Recently, Hamada and coworkers reported a similar type of cyclization using Sc(OTf)₃ as a catalyst and proposed the cyclobutane ring formation through zwitterionic intermediates: Nakano S, Kakugawa K, Nemoto T, Hamada Y. Adv. Synth. Catal. 2014; 356: 2088

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• 24 Typical Procedure for the Carbonyl-Ene Cyclization of (–)-Citronellal (Table 1, Entry 1) A mixture of (–)-citronellal (1, 77 mg, 0.5 mmol), thiourea (TU, 25 mg, 0.05 mmol), and trityl bromide (I, 16 mg, 0.05 mmol) in anhydrous CH₂Cl₂ (5 mL) was stirred at r.t., and the reaction progress was monitored by TLC. After completion, the mixture was concentrated in vacuo, and the residue was purified by column chromatography (eluted with hexane–Et₂O, 9:1) to give 2 (45 mg, 58.4%) and 3 (29 mg, 37.7%). (+)-Isopulegol (2) ^18i,25 Colorless liquid; R_f = 0.30 (hexane–EtOAc, 5:1). FTIR (neat): ν = 3408, 1645, 1455, 1375 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.87–1.02 (m, 2 H), 0.95 (d, J = 6.5 Hz, 3 H), 1.32 (dq, J = 11.5, 3.5 Hz, 1 H), 1.46–1.55 (m, 1 H), 1.66–1.70 (m, 2 H), 1.71 (s, 3 H), 1.89 (ddd, J = 12.5, 10.0, 3.0 Hz, 2 H), 2.04 (dt, J = 12.0, 3.0 Hz, 1 H), 3.46 (dt, J = 10.0, 4.0 Hz, 1 H), 4.86 (s, 1 H), 4.90 (s, 1 H). ¹³C NMR (125.8 MHz, CDCl₃): δ = 19.18, 22.22, 29.64, 31.45, 34.33, 42.64, 54.15, 70.35, 112.84, 146.63. (–)-Neoisopulegol (3) ¹⁸ⁱ,²⁵ Colorless liquid; R_f = 0.41 (hexane–EtOAc, 5:1). FTIR (neat): ν = 3453, 1644, 1455, 1446, 1390, 1374 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.89 (d, J = 6.0 Hz, 3 H), 0.95 (dq, J = 12.0, 3.5 Hz, 2 H), 1.13 (t, J = 13.0 Hz, 1 H), 1.43–1.47 (m, 1 H), 1.48 (s, 1 H), 1.67–1.77 (m, 2 H), 1.79 (s, 3 H), 1.98 (d, J = 12.0 Hz, 2 H), 3.99 (s, 1 H), 4.79 (s, 1 H), 4.95 (s, 1 H). ¹³C NMR (125.8 MHz, CDCl₃): δ = 22.23, 22.77, 23.94, 25.81, 34.76, 40.91, 48.40, 66.32, 111.29, 147.34. General Procedure for the High-Pressure-Promoted Reaction of Unsaturated Carbonyl Compounds or Activated Dienes All high-pressure reactions were performed in a Hikari-Koatsu HR-15-B3 apparatus, which is designed for pressures up to 1.0 GPa. A mixture of aldehyde or diene (0.2 mmol), thiourea (TU, 10 mg, 0.02 mmol), and trityl bromide (I, 6.5 mg, 0.02 mmol) in anhydrous CH₂Cl₂ (2 mL) was reacted at 1.0 GPa and at r.t. for the period shown in Tables 2 and 3. After releasing the pressure, the mixture was concentrated in vacuo, and the residue was purified by column chromatography (eluted with hexane–Et₂O). trans-2-(1-Methylethenyl)cyclohexanol (trans-6, Table 2, Entry 8) ²⁶ Colorless liquid; R_f = 0.28 (hexane–EtOAc, 5:1). FTIR (neat): ν = 3419, 1645, 1449, 1277 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.13–1.30 (m, 5 H), 1.61 (br s,1 H), 1.65 (s, 3 H), 1.69–1.73 (m, 1 H), 1.84–1.90 (m, 2 H), 1.98–2.02 (m, 1 H), 3.36 (dt, J = 9.6, 4.0 Hz, 1 H), 4.79 (s, 1 H), 4.83 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.14, 24.82, 25.61, 30.12, 34.03, 54.52, 70.66, 112.78, 146.60. cis-2-(1-Methylethenyl)cyclohexanol (cis-6, Table 2, Entry 8) ²⁶ Colorless liquid; R_f = 0.35 (hexane–EtOAc, 5:1). FTIR (neat): ν = 3447, 1643, 1446, 1374 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.27 (tq, J = 12.4, 3.2 Hz, 2 H), 1.42–1.52 (m, 4 H), 1.61 (tq, J = 13.6, 3.2 Hz, 1 H), 1.67 (dq, J = 13.6, 3.2 Hz, 1 H), 1.79 (s, 3 H), 2.01 (dt, J = 15.6, 2.0 Hz, 2 H), 3.98 (br s, 1 H), 4.78 (s, 1 H), 4.95 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.68, 22.65, 23.85, 25.93, 32.15, 48.59, 65.75, 111.23, 147.53. Compound 12 (Table 3, Entry 1) Colorless oil; R_f = 0.46 (hexane–Et₂O, 10:1). FTIR (KBr): ν = 1751, 1732, 1644, 1498, 1456, 1376 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.82 (d, J = 6.5 Hz, 3 H), 0.88 (dq, J = 12.5, 3.5 Hz, 1 H), 1.06 (q, J = 12.5 Hz, 1 H), 1.30–1.39 (m, 2 H), 1.59 (s, 3 H), 1.60–1.72 (m, 3 H), 2.04 (dt, J = 11.5, 3.0 Hz, 1 H), 2.11 (tt, J = 11.5, 3.5 Hz, 1 H), 3.61 (d, J = 3.5 Hz, 1 H), 4.64 (s, 1 H), 4.70 (s, 1 H), 5.12(5) (ABq, J _AB = 12.0 Hz, 2 H), 5.13(0) (ABq, J _AB = 12.0 Hz, 2 H), 7.26–7.35 (m, 10 H). ¹³C NMR (125.8 MHz, CDCl₃): δ = 18.83, 22.39, 32.20, 32.63, 34.55, 36.41, 39.95, 48.53, 53.28, 66.62, 66.82, 112.55, 128.11 (×2), 128.20, 128.26, 128.45 (×4), 128.50 (×2), 135.50, 135.53, 147.42, 168.31, 169.48. HRMS: m/z calcd for C₂₇H₃₂O₄: 420.2301; found: 420.2302. Compound 13 (Table 3, Entry 1) Colorless oil; R_f = 0.53 (hexane–Et₂O, 10:1). FTIR (KBr): ν = 1732, 1456, 1242 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.86 (d, J = 6.5 Hz, 3 H), 0.94–1.06 (m, 2 H), 1.03 (s, 3 H), 1.17 (dq, J = 12.0, 3.5 Hz, 1 H), 1.25 (s, 3 H), 1.51–1.55 (m, 2 H), 1.68–1.73 (m, 2 H), 1.97 (dt, J = 12.0, 2.5 Hz, 1 H), 2.26 (dt, J = 12.0, 2.5 Hz, 1 H), 5.10 (ABq, J _AB = 12.5 Hz, 2 H), 5.11 (ABq, J _AB = 12.5 Hz, 2 H), 7.22–7.30 (m, 10 H). ¹³C NMR (125.8 MHz, CDCl₃): δ = 20.12, 22.63, 23.88, 26.26, 33.23, 34.89, 35.59, 43.65, 46.87, 47.92, 64.08, 66.23, 66.39, 127.91, 128.00, 128.04, 128.12 (×2), 128.37, 128.39 (×4), 135.79 (×2), 168.96, 170.09. Anal. Calcd (%) for C₂₇H₃₂O₄: C, 77.11; H, 7.67. Found: C, 76.71; H, 7.68.
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