A New Route to 1,3-bis-Exocyclic Dienes Using a Palladium-mediated
Cyclization/Coupling Reaction of Conjugated Enynes with Organic Halides and Triflates

Abstract

The palladium catalyzed tandem cyclization/coupling reaction of conjugated enynes having a stabilizing carbon nucleophile with unsaturated halides or triflate afforded stereodefined functionalized 1,3-bis-exocyclic dienes. Moderate yields were obtained with substrates of type 1. However, higher homologs of type 2 led to the formation of functionalized 1,3-bis-exocyclic dienes and hexatrienes in good yields. An initial study on the sequential cyclization/coupling reaction/electrocyclization in a one-pot procedure leading to cyclohexadienes is also presented.

palladium - cyclizations - enynes - dienes - electrocyclization

References

1a Tsuji J. Palladium Reagents and Catalysts, Innovations in Organic Chemistry   Wiley; Chichester: 1995. 

1b

Tetrahedron Symposium-in-Print, 1996, 52, 35

1c Metal-catalysed Cross-coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  p.99 

1d Takacs JM. Weidner JJ. Newsome PW. Takacs BE. Chidambaram R. Shoemaker R. J. Org. Chem.  1995,  60:  5261 ; and references cited therein

2a Balme G. Bouyssi D. Tetrahedron  1994,  50:  403 

2b Coudanne I. Balme G. Synlett  1998,  998 

2c Bruyère D. Gaignard G. Bouyssi D. Balme G. Lancelin JM. Tetrahedron Lett.  1997,  38:  827 

2d Garçon S. Vassiliou S. Cavicchioli M. Hartmann B. Monteiro N. Balme G. J. Org. Chem.  2001,  66:  4069 ; and references cited therein

2e Balme G. Bouyssi D. Monteiro N. In Handbook of Organopalladium Chemistry for Organic Synthesis   Negishi E.-i. Wiley Interscience; New York: 2002.  p.2245 

For some examples using organometallic compounds see:

3a Nugent WA. Thorn DL. Harlow RL. J. Am. Chem. Soc.  1987,  109:  2788 

3b Bailey WF. Wachter-Jurcsak NM. Pineau MR. Ovaska TV. Warren RR. Lewis CE. J. Org. Chem.  1996,  61:  8216 

3c Trost BM. Shi Y. J. Am. Chem. Soc.  1993,  115:  12491 

3d Trost BM. Romero DL. Rise F. J. Am. Chem. Soc.  1994,  116:  4268 

3e Grigg R. Stevenson P. Worakun T. Tetrahedron  1988,  44:  2033 

3f Le Paih J. Rodríguez DC. Dérien S. Dixneuf PH. Synlett  2000,  95 

4a Cousseau J. Synthesis  1980,  805 

4b Barton TJ. Lin J. Ijadi-Maghsoodi S. Power MD. Zhang X. Ma Z. Shimizu H. Gordon MS. J. Am. Chem. Soc.  1995,  117:  11695 

5

The palladium-diphenylphosphinoethane was preformed by heating Pd(OAc)₂ (5 mol%) and dppe (5 mol%) in the presence of 1-heptene (10 mol%, THF, 50 °C) until a homogeneous dark red solution was obtained.

The palladium(0) catalyst generated in situ by reduction of PdCl₂(PPh₃)₂ with n-BuLi has been found particularly effective in related carbopalladation reactions:

6a

See ref. [2d]

6b Bottex M. Cavicchioli M. Hartmann B. Monteiro N. Balme G. J. Org. Chem.  2001,  175 

7

The demethoxycarbonylation of malonate ester using Krapcho’s conditions generally needs prolonged heating in polar solvent. The strain generated by the two contiguous exocyclic double bonds and the malonate could explain this rather mild conditions.

8 Bouyssi D. Balme G. Fournet G. Monteiro N. Goré J. Tetrahedron Lett.  1991,  32:  1641 

9a Fournet G. Balme G. Goré J. Tetrahedron  1991,  47:  6293 

9b Coudanne I. PhD Dissertation   Université Claude Bernard; Lyon: 1997. 

10 Klusener PAA. Kulik W. Brandsma L. J. Org. Chem.  1987,  52:  5261 

11

Only traces of the corresponding coupling product were observed which were easily removed by flash chromatography.

12

Experimental Procedure for the Synthesis of 6a:
Potassium hydride (35% in mineral oil) was washed with anhyd THF, dried and stored under nitrogen prior to use.
To a suspension of KH (48 mg, 1.2 mmol) in 3 mL of anhyd THF was added 18-C-6 (53 mg, 0.2 mmol), enyne 2a (191 mg, 1 mmol) in 4 mL of THF, and iodobenzene (170 µL, 1.5 mmol). This mixture was stirred at r.t. for 15 min. In a separate flask, n-BuLi (2 M in hexanes) was added dropwise at r.t. to a suspension of PdCl₂(PPh₃)₂ (35 mg, 0.05 mmol) in 3 mL of THF until the mixture becomes dark green. After heating at reflux for 5 min and cooling, the mixture turned to a dark red homogeneous solution and was added at r.t. via a cannula to the cyanoester anion prepared above. The resulting mixture was then stirred at 30 °C for 3 h (monitored by TLC until completion). The solution was then filtered through a short pad of silica gel (eluting with diethyl ether) and the solvent was removed under reduced pressure. The residue was purified by flash chromatography with petroleum ether/Et₂O 80/20 to afford 6a as a pale yellow solid (206 mg, 77%). ¹H NMR (CDCl₃, 300 MHz, ppm): δ = 1.94 (2 H, m), 2.17 (1 H, dt, J = 14.0, 6.5 Hz), 2.43 (2 H, t, J = 6.5 Hz), 2.60 (1 H, dt, J = 14.0, 5.5 Hz), 3.85 (3 H, s), 4.81 (1 H, d, J = 1.1 Hz), 5.02 (1 H, d, J = 1.5 Hz), 6.63 (1 H, s), 7.18-7.30 (3 H, m), 7.34 (2 H, m). ¹³C NMR (CDCl₃, 50 MHz, ppm): δ = 23.46, 35.36, 35.44, 53.19, 53.66, 117.35, 117.94, 127.44, 128.04, 128.07, 128.95, 135.73, 135.76, 141.05, 167.13. Anal. Calcd for C₁₇H₁₇NO₂: C, 76.38; H, 6.41; N, 5.24. Found: C, 76.43; H, 6.50; N, 5.19.
The E-configuration of this isomer was deduced from differential NOE experiments in the ¹H NMR.

For related examples of palladium catalyzed reaction combined with 6-π electrocyclization processes see:

13a

See ref. [2c]

13b Gilchrist TL. Summersell RJ. Tetrahedron Lett.  1987,  28:  1469 

13c Gilchrist TL. Healy MAM. J. Chem. Soc., Perkin Trans. 1  1992,  749 

13d Trost BM. Pfrengle W. Urabe H. Dumas J. J. Am. Chem. Soc.  1992,  114:  1923 

13e Grigg R. Savic V. Tetrahedron Lett.  1996,  36:  6565 

13f von Zezschwitz P. Petry F. de Meijere A. Chem.-Eur. J.  2001,  7:  4035 

Similar results were recently reported for palladium catalyzed tandem cyclization/coupling reactions involving commercial β-bromostyrene:

14a

See ref. [6]

14b Arcadi A. Cacchi S. Cassetta A. Fabrizi G. Parisi LM. Synlett  2001,  1605