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Synlett 2010(17): 2583-2588  
DOI: 10.1055/s-0030-1258777
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Morita-Baylis-Hillman Alkylation of Unsaturated Thioesters

Marie E. Krafft*, Kimberly A. Seibert, Thomas F. N. Haxell
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Fl 32306-4390, USA
Fax: +1(850)6447409; e-Mail: mek@chem.fsu.edu;
Further Information

Publication History

Received 19 July 2010
Publication Date:
30 September 2010 (online)

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Abstract

The Morita-Baylis-Hillman alkylation reaction with unsaturated thioesters is described. Five- and six-membered rings are formed with ease and in excellent yields. The method is high yielding with either stoichiometric or catalytic amounts of tributylphosphine.

Key words

cyclization - alkylation - thioesters - organocatalysis - Morita-Baylis-Hillman reaction

    References and Notes

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  • 11a

    Compound 2: ¹H NMR (500 MHz, CDCl3): δ = 6.83 (td, J = 7.0, 15.5 Hz, 1 H), 6.16 (td, J = 1.3, 15.5 Hz, 1 H), 3.41 (t, J = 6.6 Hz, 2 H), 2.95 (q, J = 7.5 Hz, 2 H), 2.38 (ddt, J = 1.3, 7.0, 7.0 Hz, 2 H), 2.03 (tt, J = 6.6, 7.0 Hz, 2 H), 1.28 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.6, 142.4, 129.5, 32.4, 30.6, 30.2, 23.0, 14.6. HRMS (FAB+): m/z [M + Na] calcd for C8H13BrOSNa: 259.9766; found: 258.9768. FTIR (neat): 2965, 2960, 2872, 1667, 1633, 1436, 1265, 1026, 970 cm-¹. Anal. Calcd for C8H13OBrS: C, 40.52; H, 5.53. Found: C, 40.13; H, 5.53.

  • 11b

    Compound 3: ¹H NMR (500 MHz, CDCl3): δ = 6.83 (td, J = 7.1, 15.4 Hz, 1 H), 6.16 (td, J = 1.3, 5.4 Hz, 1 H), 3.41 (t, J = 6.7 Hz, 2 H), 2.95 (t, J = 7.3 Hz, 2 H), 2.37 (ddt, J = 1.3, 7.1, 7.1 Hz, 2 H), 2.03 (tt, J = 6.7, 7.1 Hz, 2 H), 1.59 (tt, J = 7.3, 7.3 Hz, 2 H), 1.41 (qt, J = 7.3, 7.3 Hz, 2 H), 0.92 (t, J = 7.3 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.4, 142.2, 129.5, 32.3, 31.4, 30.6, 30.1, 28.2, 21.7, 13.4. HRMS (FAB+): m/z [M + Na] calcd for C10H17OBrNa: 287.00813; found: 287.00812. FTIR (neat): 2959, 2930, 2872, 1671, 1632 cm-¹. Anal. Calcd for C10H17OBr: C, 45.29; H, 6.46. Found: C, 45.57; H, 6.57.

  • 11c

    Compound 4: ¹H NMR (500 MHz, CDCl3): δ = 6.75 (td, J = 7.1, 15.5 Hz, 1 H), 6.06 (td, J = 1.3, 15.5 Hz, 1 H), 3.41 (t, J = 6.6 Hz, 2 H), 2.34 (tdd, J = 1.3, 7.1, 7.1 Hz, 2 H), 2.01 (tt, J = 6.6, 7.1 Hz, 2 H), 1.50 (s, 9 H). ¹³C NMR (75 MHz, CDCl3): δ = 190.4, 141.4, 130.3, 47.9, 32.5, 30.7, 30.2, 29.8. HRMS (FAB+): m/z [M + Na] calcd for C10H17OBrSNa: 287.00825; found: 287.00812. FTIR (neat): 2962, 1667, 1630, 1454, 1363, 968 cm-¹. Anal. Calcd for C10H17OBrS: C, 45.29; H, 6.46. Found: C, 45.54; H, 6.50.

  • 11d

    Compound 5: Treatment of bromide 2 (237 mg, 1 mmol), with tributylphosphine (0.23 mL, 1 mmol) in t-BuOH (2 mL) followed by addition of KOH (56 mg, 1 mmol) and BnEt3NCl (23 mg, 0.1 mmol) in CH2Cl2-H2O (10 mL, 1:1) yielded enone 5 in 99% yield (155 mg). ¹H NMR (500 MHz, CDCl3): δ = 6.79 (tt, J = 2.2, 2.4 Hz, 1 H), 2.93 (q, J = 7.4 Hz, 2 H), 2.62 (dtt, J = 2.2, 2.3, 7.6 Hz, 2 H), 2.51 (tdt, J = 2.3, 2.4, 7.6 Hz, 2 H), 1.96 (tt, J = 7.6, 7.6 Hz, 2 H), 1.27 (t, J = 7.4 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 188.9, 144.0, 141.4, 33.2, 31.0, 22.8, 22.7, 13.4. HRMS (CI+): m/z [M + H] calcd for C8H13OS: 157.06899; found: 157.06872. FTIR (neat): 2957, 2871, 1655, 1459, 1154 cm-¹. Anal. Calcd for C8H12OS: C, 61.50; H, 7.74. Found: C, 61.03; H, 7.65.

  • 11e

    Compound 6: ¹H NMR (500 MHz, CDCl3): δ = 6.80 (tt, J = 2.1, 2.3 Hz, 1 H), 2.93 (t, J = 7.4 Hz, 2 H), 2.62 (dtt, J = 2.1, 2.2, 7.6 Hz, 2 H) 2.51 (tdt, J = 2.2, 2.3, 7.6 Hz, 2 H), 1.96 (tt, J = 7.6, 7.6 Hz, 2 H), 1.58 (m, 2 H), 1.41 (tq, J = 7.4, 7.4 Hz, 2 H), 0.94 (t, J = 7.4 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.1, 144.1, 141.5, 33.4, 31.7, 31.2, 28.1, 22.9, 22.0, 13.6. HRMS (CI+): m/z [M+] calcd for C10H16OS: 185.0999; found: 185.1000. FTIR (neat): 2958, 2930, 1655, 1613, 1156 cm-¹. Anal. Calcd for C10H16OS: C, 65.17; H, 8.75. Found: C, 64.82; H, 8.87.

  • 11f Compound 7: Kishimoto N. Fujimoto T. Yamamoto I. J. Org. Chem.  1999,  64:  5988 
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  • 11g

    Compound 8: ¹H NMR (500 MHz, CDCl3): δ = 6.86 (td, J = 6.9, 15.4 Hz, 1 H), 6.12 (td, J = 1.5, 15.4 Hz, 1 H), 3.41 (t, J = 6.6 Hz, 2 H), 2.95 (q, J = 7.3 Hz, 2 H), 2.23 (dtd, J = 1.5, 7.1, 7.1 Hz, 2 H), 1.89 (tt, J = 6.6, 7.1 Hz, 2 H), 1.64 (tt, J = 7.1, 7.1 Hz, 2 H), 1.28 (t, J = 7.3 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.7, 143.9, 129.0, 33.0, 31.9, 31.0, 26.3, 22.9, 14.7. HRMS (FAB+): m/z [M + Na] calcd for C9H15OBrSNa: 272.9927; found: 272.9925. FTIR (neat): 2930, 1670, 1632, 1451, 1265, 969 cm-¹. Anal. Calcd for C9H15OBrS: C, 43.03; H, 6.02. Found: C, 43.36; H, 5.98.

  • 11h Compound 9: Schaumann E. Mergardt B. J. Chem. Soc., Perkin Trans. 1: Organic and Bioorganic Chem.  1989,  1361 
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  • 11i

    Compound 10: ¹H NMR (500 MHz, CDCl3): δ = 6.70 (td, J = 7.8, 15.4 Hz, 1 H), 6.15 (td, J = 1.2, 15.4 Hz, 1 H), 4.23 (ABq, J = 7.1, 7.1 Hz, 2 H), 4.22 (ABq, J = 7.1, 7.1 Hz, 2 H), 3.36 (t, J = 8.2 Hz, 2 H), 2.94 (q, J = 7.4 Hz, 2 H) 2.77 (dd, J = 1.2, 7.8 Hz, 2 H), 2.45 (t, J = 8.2 Hz, 2 H), 1.28 (t, J = 7.4 Hz, 3 H), 1.27 (t, J = 7.1 Hz, 6 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.3, 169.5, 137.5, 132.2, 61.9, 57.2, 36.7, 36.2, 26.6, 23.1, 14.6, 13.9. HRMS (FAB+): m/z [M + Na] calcd for C15H23O5BrSNa: 417.0340; found: 417.0347. FTIR (neat): 2980, 2934, 1730, 1671, 1633, 1443, 1261 cm-¹. Anal. Calcd for C15H23O5BrS: C, 45.57; H, 5.86. Found: C, 45.47; H, 5.95.

  • 11j

    Compound 11: ¹H NMR (500 MHz, CDCl3): δ = 6.89 (tt, J = 1.8, 4.0 Hz, 1 H), 4.19 (ABq, J = 7.1, 7.1 Hz, 2 H), 4.19 (ABq, J = 7.1, 7.1 Hz, 2 H), 2.91 (q, J = 7.4 Hz, 2 H), 2.76 (td, J = 2.4, 4.0 Hz, 2 H), 2.39 (dtt, J = 1.8, 2.4, 6.4 Hz, 2 H), 2.18 (t, J = 6.4 Hz, 2 H), 1.26 (t, J = 7.4 Hz, 3 H), 1.25 (t, J = 7.1 Hz, 6 H). ¹³C NMR (75 MHz, CDCl3): δ = 192.0, 170.7, 137.0, 134.2, 61.5, 52.4, 30.9, 27.0, 22.9, 21.2, 14.7, 13.9. HRMS (CI+): m/z [M + H] calcd for C15H23O5S: 315.1262; found: 315.1266. FTIR (neat): 2957, 2930, 2871, 1655, 1156 cm-¹. Anal. Calcd for C15H22O5S: C, 57.30; H, 7.05. Found: C, 57.34; H, 7.07.

  • 11k

    Compound 12: ¹H NMR (500 MHz, CDCl3): δ = 6.67 (td, J = 7.6, 15.3 Hz, 1 H), 6.15 (br d, J = 15.3 Hz, 1 H), 3.76 (s, 6 H), 3.35 (t, J = 8.2 Hz, 2 H), 2.94 (t, J = 7.3 Hz, 2 H), 2.78 (dd, J = 1.1, 7.6 Hz, 2 H), 2.46 (t, J = 8.2 Hz, 2 H), 1.58 (tt, J = 7.3, 7.3 Hz, 2 H), 1.40 (qt, J = 7.3, 7.3 Hz, 2 H), 0.92 (t, J = 7.3 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.2, 169.9, 137.0, 132.2, 57.3, 52.8, 36.6, 36.2, 31.4, 28.4, 26.5, 21.8, 13.5. HRMS (FAB+): m/z [M + Na] calcd for C15H23O5BrSNa: 417.03409; found: 417.03472. FTIR (neat): 2956, 1734, 1670, 1437, 1264 cm-¹. Anal. Calcd for C15H23O5BrS: C, 45.57; H, 5.86. Found: C, 45.57; H, 6.17.

  • 11l

    Compound 13: ¹H NMR (500 MHz, CDCl3): δ = 6.91 (tt, J = 1.5, 4.0 Hz, 1 H), 3.73 (s, 6 H), 2.90 (t, J = 7.3 Hz, 2 H), 2.78 (td, J = 2.2, 4.0 Hz, 2 H), 2.38 (dtt, J = 1.5, 2.2, 6.4 Hz, 2 H), 2.19 (t, J = 6.4 Hz, 2 H), 1.56 (tt, J = 7.3, 7.4 Hz, 2 H), 1.39 (tq, J = 7.4, 7.4 Hz, 2 H), 0.92 (t, J = 7.4 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 192.1, 171.2, 137.2, 134.0, 52.8, 52.5, 31.6, 31.1, 28.3, 27.2, 22.0, 21.3, 13.6. HRMS (CI+): m/z [M + H] calcd for C15H23O5S: 315.12677; found: 315.12662. FTIR (neat): 2955, 2872, 1736, 1651, 1257 cm-¹. Anal. Calcd for C15H22O5S: C, 57.30; H, 7.05. Found: C, 57.16; H, 7.20.

  • 11m

    Compound 14: ¹H NMR (500 MHz, CDCl3): δ = 6.59 (td, J = 7.6, 15.3 Hz, 1 H), 6.06 (td, J = 1.2, 15.3 Hz, 1 H), 3.76 (s, 6 H), 3.35 (t, J = 8.1 Hz, 2 H), 2.76 (dd, J = 1.2, 7.6 Hz, 2 H), 2.45 (t,
    J = 8.1 Hz, 2 H), 1.49 (s, 9 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.7, 170.0, 136.0, 133.0, 57.3, 52.9, 48.2, 36.6, 36.1, 29.7, 26.6. HRMS (FAB+): m/z [M + Na] calcd for C15H23O5BrSNa: 417.03471; found: 417.02472. FTIR (neat): 2956, 1734, 1667, 1631, 1435, 1264 cm-¹. Anal. Calcd for C15H23O5BrS: C, 45.57; H, 5.86. Found: C, 45.47; H, 5.95.

  • 11n

    Compound 15: ¹H NMR (500 MHz, CDCl3): δ = 6.86 (tt, J = 2.0, 4.4 Hz, 1 H), 3.73 (s, 6 H), 2.73 (td, J = 2.2, 4.0 Hz, 2 H), 2.32 (dtt, J = 2.2, 2.2, 6.4 Hz, 2 H), 2.16 (t, J = 6.4 Hz, 2 H), 1.47 (s, 9 H). ¹³C NMR (75 MHz, CDCl3): δ = 193.0, 171.3, 138.0, 133.2, 52.9, 52.5, 47.6, 31.1, 29.9, 28.3, 27.3, 21.6. HRMS (CI+): m/z [M+] calcd for C15H22O5S: 315.12718; found: 315.12662. FTIR (neat): 2954, 1735, 1645, 1257 cm-¹. Anal. Calcd for C15H22O5S: C, 57.30; H, 7.05. Found: C, 57.66; H, 7.21.

  • 11o

    Compound 16: ¹H NMR (500 MHz, CDCl3): δ = 6.70 (dd, J = 8.2, 15.7 Hz, 1 H), 6.13 (dd, J = 1.0, 15.7 Hz, 1 H), 3.40 (ABt, J = 9.7, 6.5 Hz, 1 H), 3.33 (ABt, J = 9.7, 6.5 Hz, 1 H), 2.95 (q, J = 7.4 Hz, 2 H), 2.57 (m, 1 H), 1.94 (ABdt, J = 14.0, 7.0, 7.0 Hz, 1 H), 1.91 (ABdt, J = 14.0, 7.0, 7.0 Hz, 1 H), 1.28 (t, J = 7.4 Hz, 3 H), 1.10 (d, J = 6.8 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.6, 147.5, 127.9, 43.9, 38.2, 34.7, 30.9, 26.6, 25.8, 23.2, 22.9, 18.8, 14.6, 14.5, 14.4. HRMS (FAB+): m/z [M + Na] calcd for C9H15OBrNaS: 272.99276; found: 272.99247. FTIR (neat): 2965, 1670, 1631, 1453 cm-¹. Anal. Calcd for C9H15OBrS: C, 43.03; H, 6.02. Found: C, 43.29; H, 6.23.

  • 11p

    Compound 18: ¹H NMR (500 MHz, CDCl3): δ = 6.98 (dd, J = 9.2, 15.5 Hz, 1 H), 6.23 (dd, J = 0.7, 15.5 Hz, 1 H), 3.25 (dd, J = 7.1, 10.0 Hz, 1 H), 3.14 (dd, J = 8.2, 10.0 Hz, 1 H), 2.96 (ABq, J = 15.0, 7.5 Hz, 1 H), 2.96 (ABq, J = 15.0, 7.5 Hz, 1 H), 2.78 (dddd, J = 4.0, 4.0, 8.0, 9.1 Hz, 1 H), 1.98 (ddddd, J = 4.0, 4.0, 7.1, 8.2, 10.8 Hz, 1 H), 1.3-1.75 (m, 7 H), 1.29 (t, J = 7.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 189.7, 143.1, 130.0, 42.6, 40.1, 36.6, 30.2, 27.2, 24.8, 23.1, 21.6, 14.7. HRMS (FAB+): m/z [M + Na] calcd for C12H19OBrSNa: 313.02361; found: 313.02377. FTIR (neat): 2930, 2856, 1670, 1628, 1449 cm-¹. Anal. Calcd for C12H19OBrS: C, 49.49; H, 6.58. Found: C, 49.70; H, 6.53.

  • 11q

    Compound 19: HRMS (CI+): m/z [M + Na] calcd for C12H18OS: 211.1152; found: 211.1157. Anal. Calcd for C12H18OS: C, 68.52; H, 8.63. Found: C, 68.27; H, 8.67.

  • 11r

    Catalysis of Reactions of α,β-Unsaturated Thioesters in the MBH Reaction: General Procedure of the Catalytic MBH Alkylation Reaction of Thioesters: A solution of thioester 2 (237 mg, 1 mmol) in CH2Cl2-t-BuOH (1:1; 2 mL, 0.5 M), and H2O (10 mL, 0.1 M) with BnEt3NCl (23 mg, 0.1 mmol) and KOH (56 mg, 1 mmol) was treated with tributylphosphine (0.45 mL, 0.2 mmol). The reaction was stirred in a resealable tube until complete consumption of starting material as indicated by TLC. The organic layer was then extracted with CH2Cl2, dried over anhyd Na2SO4 and concentrated in vacuo. Purification via column chroma-tography gave the desired product 5 (152 mg, 97%).