A Stereoselective Suzuki Cross-Coupling Strategy for the Synthesis of Ethyl-Substituted Conjugated Dienoic Esters and Conjugated Dienones

Abstract

A stereoselective approach towards ethyl-substituted conjugated dienoic esters and dienones utilising a Suzuki cross-coupling reaction has been achieved. In addition, a method for their conversion into the corresponding ethyl ketones is presented.

Key words

cross-coupling - dienoic esters - Suzuki reaction - stereoselective - triflate

References and Notes

• For example:
• 1a Carotenoids: Isolation and Analysis   Part 1A:  Britton G. Liaaen-Jensen S. Pfander H. Birkhäuser; Basel: 1995. 
• 1b Key to Carotenoids   Pfander H. Birkhäuser; Basel: 1987. 
• 2 Wittig G. Geissler G. Justus Liebigs Ann. Chem.  1953,  580:  44 
• 3a Horner L. Hoffmann HMR. Wippel HG. Chem. Ber.  1958,  91:  61 
• 3b Horner L. Hoffmann HMR. Wippel HG. Klahre G. Chem. Ber.  1959,  92:  2499 
• 3c Wadsworth WS. Emmons WD. J. Org. Chem.  1961,  83:  1733 
• 4 Julia M. Paris J.-M. Tetrahedron Lett.  1973,  14:  4833 
• For example:
• 5a Wada A. Ieki Y. Nakamura S. Ito M. Synthesis  2005,  1581 
• 5b Wada A. Fukunaga K. Ito M. Synlett  2001,  800 
• 6a Suzuki A. Miyaura N. Chem. Rev.  1995,  95:  2457 
• 6b Handbook of Organopalladium Chemistry for Organic Synthesis   Negishi E.-I. de Meijere A. Wiley-Interscience; New York: 2002. 
• 7 Saulnier MG. Kadow JF. Tun MM. Langley DR. Vyas DM. J. Am. Chem. Soc.  1989,  111:  8320 
• 8 Hansen AL. Skrydstrup T. J. Org. Chem.  2005,  70:  5997 
• 9a Lyapkalo IM. Webel M. Reißig H.-U. Eur. J. Org. Chem.  2002,  1015 
• 9b Bräse S. de Meijere A. Angew. Chem., Int. Ed. Engl.  1995,  34:  2545 ; Angew. Chem. 1995, 107, 2741
• 9c Voigt K. von Zezschwitz P. Rosauer K. Lansky A. Adams A. Reiser O. de Meijere A. Eur. J. Org. Chem.  1998,  1521 
• 9d Bräse S. Synlett  1999,  1654 
• 9e Rottlaender M. Knochel P. J. Org. Chem.  1998,  63:  203 
• 9f Kreis M. Friedmann CJ. Bräse S. Chem. Eur. J.  2005,  11:  7387 
• 10 Chan TH. Brownbridge P. J. Am. Chem. Soc.  1980,  102:  3534 
• 12 Williams JM. Johnson RB. Yasuda N. Marchesini G. Tetrahedron Lett.  1995,  36:  5461 
• 13 Prepared according to: Paterson I. Florence GJ. Gerlach K. Scott JP. Sereinig N. J. Am. Chem. Soc.  2001,  123:  9535 

11

Representative Experimental Procedure: Na₂CO₃ (1.15 g, 10.8 mmol, 1.5 equiv) was dissolved in H₂O (5.4 mL) under an argon atmosphere. (E)-Trifluoromethanesulfonyloxy-pent-2-enoic acid methyl ester [(E)-4; 1.89 g, 7.20 mmol, 1.0 equiv] and (E)-2-phenylvinylboronic acid (3; 1.08 g, 7.20 mmol, 1.0 equiv) in dioxane (16 mL) were added. The solution was degassed, Pd(PPh₃)₄ (333 mg, 0.29 mmol, 0.04 equiv) was added and the mixture was heated to 80 °C for 20 h. After cooling, the reaction was quenched with H₂O (75 mL). Et₂O (80 mL) was added, the phases were separated and the aqueous phase was extracted with Et₂O (3 × 60 mL). The combined organic phases were dried over Na₂SO₄ and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, hexanes-Et₂O, 19:1) yielding (E)-10 as a yellow oil (1.20 g, 5.55 mmol, 77%).

14

Spectroscopic data for (E)-2: R _f = 0.65 (hexanes-Et₂O, 9:1). ¹H NMR (400 MHz, CDCl₃): δ = 1.18 (t, J = 7.3 Hz, 3 H, CH ₃CH₂C=C), 1.23 (t, J = 7.5 Hz, 3 H, CH ₃CH₂CO), 2.60 (q, J = 7.3 Hz, 2 H, CH₃CH ₂C=C), 2.95 (q, J = 7.5 Hz, 2 H, CH₃CH ₂CO), 6.27 (s, 1 H, C=CHCO), 6.76 (d, J = 16.2 Hz, 1 H, PhC=CH), 7.07 (d, J = 16.2 Hz, 1 H, PhCH=C), 7.32-7.45 (m, 3 H, ArH), 7.51-7.62 (m, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 8.2 (CH₃), 14.1 (CH₃), 21.1 (CH₂), 37.8 (CH₂), 123.0 (CH), 125.6 (CH), 127.0 (CH), 127.4 (CH, CAr), 128.6 (CH), 128.7 (CH, CAr), 130.9 (CH, CAr), 134.6 (CH), 136.5 (C, CAr), 156.5 (C), 201.3 (C). IR (film on KBr): 3031 (w), 2973 (m), 2935 (w), 2876 (w), 1677 (m), 1615 (w), 1577 (m), 1466 (w), 1448 (w), 1391 (w), 1172 (w), 1125 (m), 1040 (m), 962 (m), 836 (w), 750 (m), 691 (m) cm^-1. MS (EI, 70 eV): m/z (%) = 214 (73) [M⁺], 199 (30), 185 (100), 157 (32), 141 (43), 129 (54), 115 (41), 91 (32). HRMS: m/z calcd for C₁₅H₁₈O: 214.1358; found: 214.1357. Anal. Calcd for C₁₅H₁₈O: C, 84.07; H, 8.47. Found: C, 84.15; H, 8.44.

15

Spectroscopic data for (Z)-2: R _f = 0.58 (hexanes-Et₂O, 9:1). ¹H NMR (400 MHz, CDCl₃): δ = 1.04 (t, J = 7.3 Hz, 3 H, CH ₃CH₂C=C), 1.13 (t, J = 7.5 Hz, 3 H, CH ₃CH₂CO), 2.39-2.45 (m, 2 H, CH₃CH ₂C=C), 2.44-2.50 (m, 2 H, CH₃CH ₂CO), 6.02 (s, 1 H, C=CHCO), 6.76 (d, J = 16.2 Hz, 1 H, PhC=CH), 7.17-7.30 (m, 3 H, ArH), 7.45-7.50 (m, 2 H, ArH), 8.27 (d, J = 16.7 Hz, 1 H, PhCH=C). ¹³C NMR (100 MHz, CDCl₃): δ = 8.1 (CH₃), 13.9 (CH₃), 26.8 (CH₂), 37.8 (CH₂), 123.0 (CH), 125.9 (CH), 127.0 (CH), 128.5 (CH, CAr), 128.6 (CH), 128.7 (CH, CAr), 130.9 (CH, CAr), 135.3 (CH), 136.8 (C, CAr), 154.4 (C), 202.0 (C). IR (film on KBr): 2973 (m), 2936 (w), 2876 (w), 1676 (m), 1615 (m), 1579 (m), 1449 (w), 1375 (w), 1199 (w), 1127 (m), 1040 (w), 973 (m), 753 (w), 691 (m) cm^-1. MS (EI, 70 eV): m/z (%) = 214 (29) [M⁺], 185 (100), 141 (17), 129 (34), 115 (20), 91 (12). HRMS: m/z calcd for C₁₅H₁₈O: 214.1358; found: 214.1354. Anal. Calcd for C₁₅H₁₈O: C, 84.07; H, 8.47. Found: C, 84.44; H, 8.43.