Palladium Catalyzed Coupling Reaction of an Enol Nonaflate with (Vinyl)tributylstannanes and Acetylenes

Abstract

A novel method for a stereoselective synthesis of trienes and dienynes was developed by palladium catalyzed cross coupling reactions of an enol nonaflate with (vinyl)tributylstannanes and acetylenes in good to excellent yields. Here, the enol nonaflate exhibited a higher reactivity compared with the corresponding enol triflate in the coupling reactions.

enol nonaflate - palladium catalyst - coupling reaction - alkenyl stannane - acetylene

References

1 For review, see: Ritter K. Synthesis  1993,  735 

2a Yasuda N. Xavier L. Rieger DL. Li Y. DeCamp AE. Dolling U.-H. Tetrahedron Lett.  1993,  34:  3211 

2b Nicolaou KC. Sato M. Miller ND. Gunzner JL. Renaud J. Untersteller E. Angew. Chem., Int. Ed. Engl.  1996,  35:  889 

2c Sasaki M. Fuwa H. Inoue M. Tachibana K. Tetrahedron Lett.  1998,  39:  9027 

For Heck coupling of enol nonaflate, see:

3a Bräse S. de Meijere A. Angew. Chem. Int. Ed. Engl.  1995,  34:  2545 

3b Webel M. Reissig H.-U. Synlett  1997,  1141 

3c Bräse S. Synlett  1999,  1654 

For Stille, Suzuki and Sonogashira couplings of aryl nonaflate, see:

4a Rottläbder M. Knochel P. J. Org. Chem.  1998,  63:  203 

4b Stoltz BM. Kano T. Corey EJ. J. Am. Chem. Soc.  2000,  122:  9044 

4c Bellina F. Ciucci D. Vergamini P. Rossi R. Tetrahedron  2000,  56:  2533 

5a Wada A. Nomoto Y. Tano K. Yamashita E. Ito M. Chem. Pharm. Bull.  2000,  48:  1391 

5b Wada A. Fukunaga K. Ito M. Synlett  2001,  800 

5c Wada A. Babu G. Shimomoto S. Ito M. Synlett  2001,  1751 

6 Engler TA. Sampath U. Naganathan S. Velde DV. Takuasgawa F. J. Org. Chem.  1989,  54:  5712 

7 Subramanian LR. Bentz H. Hanack M. Synthesis  1973,  293 

8

¹H NMR data of enol nonaflate 2a are as follows: (300 MHz, CDCl₃) δ: 0.97 (6 H, s, Me × 2), 1.42-1.50 (2 H, m, CH₂), 1.56-1.62 (2 H, m, CH₂), 1.68 (3 H, s), 2.02 (2 H, t, J = 7 Hz), 6.21 (1 H, d, J = 12 Hz, =CH), 6.46 (1 H, d, J = 16 Hz, =CH).

9 Farina V. Krishnan B. J. Am. Chem. Soc.  1991,  113:  9585 

10

Typical coupling procedure: To a stirred solution of enol nonaflate (2a, 1 mmol),(vinyl)tributylstannane (4, 1.5 mmol), and AsPh₃ (20 mol%, 60 mg) in DMF (2 mL) was added Pd₂dba₃-CHCl₃ adduct (2.5 mol%, 26 mg) all at once under nitrogen. After stirring for an indicated period in Table [1] , the reaction was quenched with saturated aqueous NH₄Cl solution (3 mL) and extracted with diethyl ether (10 mL × 3). The extracts were washed with saturated aqueous NaCl solution (10 mL) and then dried over Na₂SO₄. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel to afford the coupled product 5.
5a: IR (CHCl₃) cm^-1: 3610, 3446, 2969, 1647; ¹H NMR (300 MHz, CDCl₃) δ: 1.00 (6 H, s, Me × 2), 1.40-1.46 (2 H, m, CH₂), 1.56-1.62 (3 H, m, CH₂ and OH), 1.69 (3 H, s, Me), 2.02 (2 H, t, J = 7 Hz, CH₂), 4.19 (2 H, t, J = 7 Hz, CH₂), 5.78 (1 H, dt, J = 15, 6 Hz, =CH), 6.03 (1 H, dd, J = 16, 10 Hz, =CH), 6.14 (1 H, d, J = 16 Hz, =CH), 6.31 (1 H, ddt, J = 15, 10, 1 Hz, =CH); HRMS (EI) C₁₄H₂₂O: requires 206.1669, found 206.1667.

11 In the case of trisubstituted olefins 5d and 5e, its stereo-chemistry was determined after conversion to the corresponding aldehyde by oxidation, respectively. See: Wada A. Hiraishi S. Takamura N. Date T. Aoe K. Ito M. J. Org. Chem.  1997,  62:  4343 

12

Typical coupling procedure: To a stirred solution of enol nonaflate (2a, 0.5 mmol), acetylene (6, 1 mmol), diisopropylamine (2 mmol, 200 mg), and CuI (15 mol%, 35 mg) in benzene (3 mL) was added Pd(PPh₃)₄ (10 mol%, 58 mg) all at once under nitrogen. After stirring for an indicated period in Table [2] , the reaction was quenched with saturated aqueous NH₄Cl solution (3 mL) and extracted with ether (10 mL × 3). The extracts were washed with saturated aqueous NaCl solution (10 mL) and then dried over Na₂SO₄. The solvent was removed under reduced pressure and the residue was purified by column chromatography on a silica gel to produce the coupled product 7.
7a: IR (CHCl₃) cm^-1: 3608, 3450, 2932, 2209, 1604; ¹H NMR (300 MHz, CDCl₃) δ: 1.00 (6 H, s, Me × 2), 1.40-1.47 (2 H, m, CH₂), 1.56-1.61 (3 H, m, CH₂ and OH), 1.70 (3 H, s, Me), 1.99 (2 H, t, J = 6 Hz, CH₂), 4.41 (2 H, d, J = 4 Hz, CH₂), 5.47 (1 H, dt, J = 16.5, 2 Hz, =CH), 6.59 (1 H, d, J = 16 Hz, =CH); HRMS (EI) C₁₄H₂₀O: requires 204.1513, found 204.1520.

13

In the case of ¹³C-labeled aldehyde 1, there was no reappearance of the peak for the conversion to the corresponding enol triflate. On the contrary, there was no trouble in preparation of the enol nonaflate.