A Novel One-Pot Cycloisomerization-Wittig Sequence with Yne-Allyl Alcohols

Abstract

Alkyne allyl alcohols 1 are cycloisomerized under Pd ­catalysis to give γ,δ-enals 2 in moderate to good yields. These mild reaction conditions are fully compatible with a subsequent Wittig olefination. Thus, the cycloisomerization-Wittig olefination sequence of yne allyl alcohols 1 and stabilized phosphorus ylides 3 furnishes 2,3,6,7-bisunsaturated carbonyl compounds 4 in moderate to good yields in a one-pot fashion.

alkynes - catalysis - domino reactions - ene reactions - Wittig reactions

References

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1d Tietze LF. Chem. Rev.  1996,  96:  115 

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2a Pd: Trost BM. Acc. Chem. Res.  1990,  23:  34 

2b Pd: Trost BM. Janssen Chim. Acta  1991,  9:  3 

2c Pd: Trost BM. Krische MJ. Synlett  1998,  1 

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2f Rh: Cao P. Wang B. Zhang X. J. Am. Chem. Soc.  2000,  122:  6490 

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2h Rh: Lei A. He M. Zhang X.
J. Am. Chem. Soc.  2002,  124:  8198 

2i Ir: Chatani N. Inoue H. Morimoto T. Muto T. Murai S. J. Org. Chem.  2001,  66:  4433 

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3b Aubert C. Buisine O. Malacria M. Chem. Rev.  2002,  102:  813 

4a Karpov AS. Rominger F. Müller TJJ. J. Org. Chem.  2003,  68:  1503 

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6a The synthesis of yne allyl alcohol substrates were performed according to: Sajiki H. Hirota K. Tetrahedron  1998,  54:  13981 

6b

The detailed protocols will be described elsewhere.

7

Typical Procedure (2e, entry 5): To a solution of Pd₂ (dba)₃·CHCl₃ (31 mg, 0.03 mmol) in dichloroethane (10 mL) were added 1e (0.312 g, 1.00 mmol) and HCOOH (92 mg, 2.0 mmol). The reaction mixture was stirred at r.t. for 2 h and then diluted with of Et₂O (150 mL). After filtration the solvents were evaporated in vacuo and the residue was chromatographed on silica gel to give 0.246 g (79%) of 2e as a yellow oil. IR (neat): 2954 (s), 2897 (w), 2844 (w), 2724 (w), 1736 (s), 1626 (m), 1436 (s), 1251 (s), 1201 (s), 1165 (s), 1122 (m), 1077 (m), 1026 (w), 961 (w), 866 (s), 841 (s), 748 (w), 693 (w) cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 0.11 (s, 9 H), 1.85 (dd, J = 10.5, 13.0 Hz, 1 H), 2.48 (ddd, J = 2.0, 8.2, 17.3 Hz, 1 H), 2.62-2.82 (m, 2 H), 2.91 (dt, J = 3.2, 17.0 Hz, 1 H), 2.96-3.05 (m, 1 H), 3.10 (d, J = 17.0 Hz, 1 H), 3.73 (s, 3 H), 3.75 (s, 3 H), 5.30 (q, J = 2.3 Hz, 1 H), 9.79 (t, J = 1.6 Hz, 1 H). ¹³C NMR (CDCl₃, 125.8 MHz): δ = -0.6 (CH₃), 38.9 (CH), 39.0 (CH₂), 40.2 (CH₂), 48.2 (CH₂), 52.7 (CH₃), 52.8 (CH₃), 58.6 (C_quat.), 120.6 (CH), 158.7 (C_quat.), 171.7 (C_quat.), 171.8 (C_quat.), 201.2 (CH). EI-MS (70 eV): m/z (%) = 312 (6) [M⁺], 297 (9) [M⁺ - CH₃], 281 (17), 270 (27), 252 (29), 237 (15), 225 (10), 209 (10), 193 (14), 163 (43), 149 (18), 137 (17), 120 (22), 89 (66), 73 (100) [Si(CH₃)₃ ⁺], 59 (30). HRMS: m/z calcd for C₁₅H₂₄O₅Si: 312.1393; found: 312.1397.

8

All compounds have been fully characterized spectroscopically and by correct elemental analysis or HRMS.

9

Typical Procedure (4e, entry 5): To a solution of Pd_{2 (}dba)₃·CHCl₃ (41 mg, 0.04 mmol) dichloroethane (10 mL) were added 1f (0.316 g, 1.00 mmol) and HCOOH (92 mg, 2.0 mmol). The reaction mixture was stirred at r.t. for 2 h and then 3a (0.627 g, 1.80 mmol) was added. Then, the reaction mixture was stirred at r.t. for 24 h before it was diluted with Et₂O (150 mL). After filtration the solvents were evaporated in vacuo and the residue was chromatographed on silica gel to give 0.308 g (80%) of 4e as a yellow oil. IR (Film): 2955 (m), 1735 (s), 1653 (m), 1492 (w), 1435 (m), 1368 (w), 1265 (s), 1203 (s), 1171 (s), 1044 (m), 752 (m), 697 (m) cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.20 (t, J = 7.2 Hz, 3 H), 1.76 (dd, J = 10.6, 12.9 Hz, 1 H), 2.16-2.30 (m, 1 H), 2.46-2.66 (m, 2 H), 2.77-2.93 (m, 1 H), 3.07-3.18 (m, 1 H), 3.29 (d, J = 17.7 Hz, 1 H), 3.61 (s, 3 H), 3.64 (s, 3 H), 4.10 (q, J = 7.2 Hz, 2 H), 5.83 (d, J = 15.4 Hz, 1 H), 6.19-6.25 (m, 1 H), 6.89 (dt, J = 7.1, 15.5 Hz, 1 H), 7.07-7.16 (m, 1 H), 7.16-7.30 (m, 4 H). ¹³C NMR (CDCl₃, 75.5 MHz): δ = 14.4 (CH₃), 36.7 (CH₂), 38.6 (CH₂), 38.9 (CH₂), 42.8 (CH), 52.7 (CH₃), 52.8 (CH₃), 58.9 (C_quat.), 60.1 (CH₂), 122.8 (CH), 123.0 (CH), 126.4 (CH), 128.2 (CH), 128.3 (CH), 137.7 (C_quat.), 143.3 (C_quat.), 146.1 (CH), 166.1 (C_quat.), 171.7 (C_quat.). UV-Vis (CH₂Cl₂): _max (ε) = 258 (18846), 286 (1135) nm. EI-MS (70 eV): m/z (%) = 386 (44) [M]⁺, 355 (6) [M - H - 2CH₃]⁺, 340 (17) [M - H - 3CH₃]⁺, 280 (22), 273 (20), 241 (19), 213 (100), 181 (10), 153 (48), 91 (18). HRMS: m/z calcd for C₂₂H₂₆O₆: 386.1729; found: 386.1735.