Organocatalysis of the Morita-Baylis-Hillman Alkylation Using ­Trialkylphosphines

Abstract

Using a catalytic amount of trialkylphosphines, alkyl halides undergo efficient intramolecular Morita-Baylis-Hillman cyclization.

alkylation - cyclization - cycloalkenone - organocatalysis - ring closure

References and Notes

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11

General Procedure: To the halide in a 0.5 M solution of t-BuOH-CH₂Cl₂ (1:1), were added a 0.2 M KOH solution (1 equiv) and BnEt₃NCl (10 mol%). The reaction mixture was then treated with tributylphosphine (20 mol%) and allowed to stir at ambient temperature until the reaction was complete (TLC analysis). For entries 1, 4 and 5 (Table [2] ), a 1.0 M solution of t-BuOH-CH₂Cl₂ (1:1) was employed for the catalytic reaction.

12

For characterization data of compounds 1-6, 9, 12-16, 19, and 22, see ref. 10a. Bromide 7: ¹H NMR (500 MHz, CDCl₃): δ = 8.45 (m, 1 H, aromatic), 8.02 (m, 1 H, aromatic), 7.98 (m, 1 H, aromatic), 7.90 (m, 2 H, aromatic), 7.56 (m, 2 H, aromatic), 7.12 (td, J = 6.0, 15.45 Hz, 1 H, CH=CHCH₂), 7.07 (d, J = 15.45 Hz, 1 H, CH=CHCH₂), 3.46 (t, J = 6.6 Hz, 2 H, BrCH ₂CH₂), 2.41 (dt, J = 6.0, 7.3 Hz, 2 H, CH=CHCH ₂), 1.97 (tt, J = 6.6, 7.5 Hz, 2 H, CH ₂CH₂Br), 1.74 (tt, J = 7.3, 7.5 Hz, 2 H, CH=CH CH₂CH ₂). ¹³C NMR (75 MHz, CDCl₃): δ = 190.3, 148.5, 135.3, 135.1, 132.4, 129.9, 129.4, 128.4, 128.3, 127.7, 126.7, 126.2, 124.4, 32.3, 32.1, 31.8, 26.6. HRMS (FAB+): m/z [M + Na] calcd for C₁₇H₁₇OBrNa: 339.0368; found: 339.0360. FTIR (neat): 2934, 1691, 1665, 1615, 1460, 1295 cm^-1. Anal. Calcd for C₁₇H₁₇OBr: C, 64.37; H, 5.40. Found: C, 64.44; H, 5.46. Bromide 8: ¹H NMR (500 MHz, CDCl₃): δ = 8.32 (m, 2 H, aromatic), 8.05 (m, 2 H, aromatic), 7.10 (td, J = 6.8, 15.4 Hz, 1 H, CH=CHCH₂), 6.89 (td, J = 1.5, 15.4 Hz, 1 H, CH=CCH₂), 3.44 (t, J = 6.6 Hz, 2 H, CH ₂Br), 2.40 (ddt, J = 1.5, 6.6, 7.2 Hz, 2 H, C=CHCH ₂), 1.94 (tt, J = 6.6, 7.2 Hz, 2 H, CH ₂CH₂Br), 1.73 (tt, J = 7.2, 7.2 Hz, 2 H, C=CHCH ₂CH₂). ¹³C NMR (75 MHz, CDCl₃): δ = 188.8, 150.8, 149.7, 142.4, 129.4, 129.2, 125.6, 123.6, 123.5, 33.1, 31.9, 31.7, 26.3. HRMS (FAB+): m/z [M + H⁺] calcd for C₁₃H₁₅O₃NBr: 312.0237; found: 312.0235. FTIR (neat): 3106, 2937, 2861, 1673, 1620, 1601, 1523, 1344 cm^-1. Anal. Calcd for C₁₃H₁₄O₃NBr: C, 50.02; H, 4.52. Found: C, 50.05; H, 4.67. Bromide 10: ¹H NMR (500 MHz, CDCl₃): δ = 8.45 (m, 1 H, aromatic), 8.03 (m, 1 H, aromatic), 7.98 (m, 1 H, aromatic), 7.90 (m, 2 H, aromatic), 7.58 (m, 2 H, aromatic), 7.14 (d, J = 15.38 Hz, 1 H, CH=CHCH₂), 7.07 (td, J = 6.6, 15.4 Hz, 1 H, CH=CHCH₂), 3.49 (t, J = 6.6 Hz, 2 H, BrCH ₂CH₂), 2.56 (dt, J = 6.6, 7.3 Hz, 2 H, CH=CHCH ₂), 2.13 (tt, J = 6.6, 7.3 Hz, 2 H, CH ₂CH₂Br). ¹³C NMR (75 MHz, CDCl₃): δ = 189.8, 146.8, 135.2, 134.8, 132.3, 129.8, 129.3, 128.3, 128.2, 127.6, 126.6, 126.5, 124.2, 32.7, 30.9, 30.7. FTIR (neat): 3055, 2930, 1665, 1617, 1291 cm^-1. Anal. Calcd for C₁₆H₁₅OBr: C, 63.38; H, 4.99. Found: C, 63.39; H, 4.93.
Enone 11: ¹H NMR (500 MHz, CDCl₃): δ = 8.32 (m, 2 H, aromatic), 8.05 (m, 2 H, aromatic), 7.08 (td, J = 7.1, 15.4 Hz, 1 H, CH=CHCH₂), 6.93 (td, J = 1.5, 15.4 Hz, 1 H, CH=CHCH₂), 3.46 (t, J = 7.0 Hz, 2 H, CH ₂Br), 2.55 (dtd, J = 1.5, 7.0, 7.1 Hz, 2 H, CH=CHCH ₂), 2.11 (tt, J = 7.0, 7.0 Hz, 2 H, CH ₂CH₂Br). ¹³C NMR (75 MHz, CDCl₃): δ = 188.8, 149.9, 149.4, 142.4, 129.3, 126.3, 123.7, 35.5, 31.0, 30.6. FTIR (neat): 2936, 2854, 1674, 1622, 1602, 1436, 1248, 1028 cm^-1. Anal. Calcd for C₁₂H₁₂O₃NBr: C, 48.34; H, 4.06; N, 4.70. Found: C, 48.67; H, 4.34; N, 4.75. Enone 17: ¹H NMR (500 MHz, CDCl₃): δ = 8.12 (m, 1 H, aromatic), 7.92 (m, 1 H, aromatic), 7.87 (m, 2 H, aromatic), 7.75 (m, 1 H, aromatic), 7.55 (m, 2 H, aromatic), 6.64 (tt, J = 2.0, 7.3 Hz, 1 H, C=CHCH₂), 2.49 (dtt, J = 2.0, 2.4, 6.1 Hz, 2 H, CH=CHCH ₂), 2.30 (ttd, J = 2.4, 6.1, 7.2 Hz, 2 H, CH ₂CH=C), 1.78 (tt, J = 6.1, 6.1 Hz, 2 H, C=CH₂CH ₂), 1.71 (tt, J = 6.1, 6.1 Hz, 2 H, C=CHCH₂CH ₂). FTIR (neat): 2918, 2849, 1638, 1465, 1282 cm^-1. Anal. Calcd for C₁₇H₁₆O: C, 86.40; H, 6.82. Found: C, 86.10; H, 6.43. Enone 18: ¹H NMR (500 MHz, CDCl₃): δ = 8.27 (m, 2 H, aromatic), 7.73 (m, 2 H, aromatic), 6.57 (tt, J = 2.0, 7.4 Hz, 1 H, C=CHCH₂), 2.43 (dtt, J = 2.0, 2.4, 6.2 Hz, 2 H, CH=CCH ₂), 2.30 (ttd, J = 2.4, 6.2, 7.6 Hz, 2 H, C=CHCH ₂), 1.75 (tt, J = 6.2, 6.2 Hz, 2 H, C=CHCH₂CH ₂), 1.69 (tt, J = 6.2, 6.2 Hz, 2 H, C=CHCH₂CH₂CH ₂). ¹³C NMR (75 MHz, CDCl₃): δ = 195.9, 149.0, 146.5, 144.4, 138.6, 129.6, 123.2, 26.2, 23.4, 21.7, 21.4. HRMS (EI+): m/z calcd for C₁₃H₁₃O₃N: 231.08948; found: 231.08955. FTIR (neat): 2933, 1648, 1301, 1522, 1350 cm^-1. Anal. Calcd for C₁₃H₁₃O₃N: C, 67.52; H, 5.67. Found: C, 67.30; H, 5.74.
Enone 20: ¹H NMR (500 MHz, CDCl₃): δ = 8.25 (m, 1 H, aromatic), 7.83-7.94 (m, 4 H, aromatic), 7.52-7.59 (m, 2 H, aromatic), 6.61 (tt, J = 1.7, 2.5 Hz, 1 H, C=CHCH₂), 2.81 (dtt, J = 1.7, 2.2, 7.5 Hz, 2 H, CH=CCH ₂), 2.67 (tdt, J = 2.2, 2.5, 7.5 Hz, 2 H, CH ₂CH=C), 2.06 (tt, J = 7.5, 7.5 Hz, 2 H, CH ₂CH₂CH=C). ¹³C NMR (75 MHz, CDCl₃): δ = 194.1, 146.7, 144.6, 136.1, 134.9, 132.2, 129.9, 129.1, 128.0, 127.8, 127.7, 126.5, 125.1, 34.3, 32.0, 22.7. HRMS (FAB+): m/z [M + Na] calcd for C₁₆H₁₄ONa: 245.0948; found: 245.0942. FTIR (neat): 2952, 1636, 1355, 1299 cm^-1. Anal. Calcd for C₁₆H₁₄O: C, 86.45; H, 6.35. Found: C, 86.41; H, 6.33. Enone 21: ¹H NMR (500 MHz, CDCl₃): δ = 8.28 (m, 2 H, aromatic), 7.84 (m, 2 H, aromatic), 6.57 (tt, J = 2.0, 12.4 Hz, 1 H, C=CHCH₂), 2.76 (dtt, J = 2.4, 7.6, 12.4 Hz, 2 H, CH=CCH ₂), 2.66 (tdt, J = 2.0, 2.4, 7.6 Hz, 2 H, C=CHCH ₂), 2.04 (tt, J = 7.6, 7.6 Hz, 2 H, C=CHCH₂CH ₂). ¹³C NMR (75 MHz, CDCl₃): δ = 192.0, 149.5, 149.1, 144.5, 144.3, 129.5, 123.4, 34.6, 31.5, 22.7. HRMS (EI+): m/z [M + Na] calcd for C₁₂H₁₁O₃N: 217.07378; found: 217.07390. FTIR (neat): 2957, 2871, 1646, 1601, 1522, 1348 cm^-1. Anal. Calcd for C₁₂H₁₁O₃N: C, 66.35; H, 5.10. Found: C, 66.21; H, 5.10.