Propargylic Phosphonium Salts in Cobalt-Catalysed Diels-Alder Reactions

Abstract

A straight forward one-pot reaction sequence consisting of a cobalt-catalysed Diels-Alder reaction for the generation of a dihydroaromatic phosphonium salt and a subsequent Wittig olefination generates polysubstituted dihydrostilbene derivatives which can optionally be oxidised by DDQ to the corresponding stilbenes. Several aldehydes, 1,3-dienes and also homopropargylic phosphonium salts can be applied.

Key words

catalysis - cobalt - 1,4-diene - stilbene - Wittig olefination

References and Notes

• For selected examples of transition-metal-catalysed [4+2] cycloadditions, see:
• 1a Lautens M. Klute W. Tam W. Chem. Rev.  1996,  96:  49 
• 1b tom Dieck H. Diercks R. Angew. Chem., Int. Ed. Engl.  1983,  22:  778 ; Angew. Chem. 1983, 95, 801
• 1c Bakhtiar R. Drader JJ. Jacobsen DB. J. Am. Chem. Soc.  1992,  114:  8304 
• 1d Wender PA. Jenkins TE. J. Am. Chem. Soc.  1989,  111:  6432 
• 1e Wender PA. Smith TE. J. Org. Chem.  1995,  60:  2962 
• 1f Jolly RS. Luedtke G. Sheehan D. Livinghouse T. J. Am. Chem. Soc.  1990,  112:  4965 
• 1g Wender PA. Jenkins TE. Suzuki S. J. Am. Chem. Soc.  1995,  117:  1843 
• 1h Brunner H. Reimer A. Bull. Chem. Soc. Fr.  1997,  134:  307 
• 1i Lautens M. Tam W. Lautens JC. Edwards LG. Crudden CM. Smith AC. J. Am. Chem. Soc.  1995,  117:  6863 
• For cobalt-catalysed Diels-Alder reactions with functionalised building blocks, see:
• 2a Hilt G. Hess W. Harms K. Org. Lett.  2006,  8:  3287 
• 2b Hilt G. Lüers S. Smolko KI. Org. Lett.  2005,  7:  251 
• 2c Hilt G. Galbiati F. Synlett  2005,  829 
• 2d Hilt G. Lüers S. Harms K. J. Org. Chem.  2004,  69:  624 
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• 2f Hilt G. Smolko KI. Lotsch BV. Synlett  2002,  1081 
• For recent examples of Wittig reactions with allylic-type phosphonium salts, see:
• 7a Ackermann M. Berger S. Tetrahedron  2005,  61:  6764 
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• 9 Hilt G. Lüers S. Polborn K. Isr. J. Chem.  2001,  41:  317 

3

The alkynyl phosphine derivatives seem to coordinate to the cobalt catalyst via the phosphorus functionality, blocking the free coordination sites necessary for the Diels-Alder reaction. Higher catalyst loading did not restore the reactivity, as it did in the case of alkynyl sulfide derivatives (ref. 2d).

4

The reduction of the amount of zinc iodide reduced the reactivity of the catalyst system considerably. The yields of dihydroaromatic intermediates or the final products 4 were not diminished by the considerable amount of inorganic components.

5

The separation of the E/Z stereoisomers is possible after column chromatography.

6

General Procedure.
Under an argon atmosphere, ZnI₂ (319 mg, 1.0 mmol, 2.0 equiv), zinc dust (20 mg, 0.3 mmol, 60 mol%) and CoBr₂ (dppe) (62 mg, 0.1 mmol, 20 mol%) were suspended in dry CH₂Cl₂ (10 mL). After formation of the active catalytic species, recognisable when the green suspension turned deep brown, prop-2-ynyl(triphenyl)phosphonium bromide (1, 191 mg, 0.5 mmol, 1.0 equiv) and 2,3-dimethyl-1,3-butadiene (0.75 mmol, 62 mg, 85 µL, 1.5 equiv) were added. The resulting mixture was stirred at r.t. for 30 min. After cooling the solution down in an ice bath, t-BuOK (281 mg, 2.5 mmol, 5.0 equiv) and 4-nitrobenzaldehyde (91 mg, 0.6 mmol, 1.2 equiv) were added at 0 °C. After the addition was completed, the reaction mixture was stirred one additional hour at ambient temperature and then filtered over a short pad of silica gel (eluent: pentane-MTBE, 1:1). The filtrate was concentrated under reduced pressure to give an oily residue that was dissolved in benzene (10 mL) and oxidised with DDQ (170 mg, 0.75 mmol, 1.5 equiv) at r.t. After 2 h the reaction mixture was washed twice with aq basic thiosulfate solution (10% NaOH, 10% Na₂S₂O₃, 2 × 10 mL). The aqueous phases were combined, extracted with MTBE (20 mL) and the combined organic phases were dried over MgSO₄. After evaporating the solvent under reduced pressure, the crude product was purified by column chromatography on silica gel (eluent: pentane-MTBE, 100:1) to give 108 mg (85%) of 4e as a yellow solid. E-isomer: ¹H NMR (500 MHz, CDCl₃): δ = 8.20 (d, 2 H, J = 8.8 Hz), 7.60 (d, 2 H, J = 8.8 Hz), 7.33 (s, 1 H), 7.29 (d, 1 H, J = 7.8 Hz), 7.22 (d, 1 H, J = 16.3 Hz), 7.16 (d, 1 H, J = 7.8 Hz), 7.08 (d, 1 H, J = 16.3 Hz), 2.31 (s, 3 H), 2.30 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 146.5, 144.2, 137.8, 137.0, 133.8, 133.4, 130.1, 128.2, 126.6, 125.1, 124.6, 124.1, 19.8, 19.6.
Z-isomer: ¹H NMR (500 MHz, CDCl₃): δ = 8.07 (d, 2 H, J = 8.7 Hz), 7.40 (d, 2 H, J = 8.7 Hz), 7.01 (s, 1 H), 7.01 (d, 1 H, J = 7.0 Hz), 6.94 (d, 1 H, J = 7.8 Hz), 6.76 (d, 1 H, J = 12.2 Hz), 6.54 (d, 1 H, J = 12.2 Hz), 2.26 (s, 3 H), 2.20 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 146.3, 144.5, 136.7, 136.5, 134.0, 133.5, 130.0, 129.7, 129.5, 127.0, 126.1, 123.4, 19.5, 19.5. IR (KBr): 3070, 2972, 1590, 1514, 1452, 1344, 1183, 1109, 972, 866, 834, 814, 750, 710, 690 cm^-1. MS (EI): m/z = 253 [M⁺], 223, 207, 192, 178, 165, 91. HRMS (EI): m/z calcd for C₁₆H₁₅NO₂: 253.1103; found: 253.1106.

8

Investigations towards the synthesis of combretastatin derivatives are underway.