A Novel One-Pot Synthesis of Phthalic Acid Derivatives Involving a Three-Component Coupling Reaction of β-Arylcrotonate and Alkynes

Abstract

Based on a versatile three-component coupling methodology, a novel synthesis of highly substituted phthalic acid derivatives is reported.

Diels-Alder reaction - annulation - β-arylcrotonate - multicomponent reaction - dimethyl acetylenedicarboxylate

References

1a Rawal VH. Michoud C. Monestel RF. J. Am. Chem. Soc.  1993,  115:  3030 

1b Rawal VH. Iwasa S. J. Org. Chem.  1994,  59:  2685 

1c Enders D. Meyer O. Liebigs Ann. Chem.  1996,  1023 

1d Kozmin SA. Rawal VH. J. Org. Chem.  1997,  62:  5252 

2a Janey JM. Iwama T. Kozmin SA. Rawal VH. J. Org. Chem.  2000,  65:  9059 

2b Kozmin SA. Janey JM. Rawal VH. J. Org. Chem.  1999,  64:  3039 

2c Overman LE. Freerks RL. Petty CB. Clizbe LA. Ono RK. Taylor GF. Jessup PJ. J. Am. Chem. Soc.  1981,  103:  2816 

2d Oppolzer W. Bieber L. Francotte E. Tetrahedron Lett.  1979,  16:  4537 

2e Neumann H. Wangelin AJV. Gördes D. Beller M. J. Am. Chem. Soc.  2001,  123:  8398 

2f Neumann H. Wangelin AJV. Gordes D. Spannenberg A. Baumann W. Beller M. Tetrahedron  2002,  58:  2381 

2g Wangelin AJV. Neumann H. Gördes D. Spannenberg A. Beller M. Org. Lett.  2001,  3:  2895 

3 Abdulla RF. Brinkmeyer RS. Tetrahedron  1979,  33:  1675 

4a Vetelino MG. Coe JW. Tetrahedron Lett.  1994,  35:  219 

4b Dupau P. Renouard T. Bozec HL. Tetrahedron Lett.  1996,  37:  7503 

4c Viau L. Senechal K. Maury O. Guégan JP. Dupau P. Toupet L. Bezec HL. Synthesis  2003,  577 

4d Riesgo EC. Jin X. Thummel RP. J. Org. Chem.  1996,  61:  3017 

5a Caron S. Vazquez E. J. Org. Chem.  2003,  68:  4104 

5b Siu J. Baxendale IR. Ley SV. Org. Biomol. Chem.  2004,  2:  160 

5c Tois J. Vahermo M. Koshinen A. Tetrahedron Lett.  2005,  46:  735 

6 Lee KY. Lee MJ. Gowrisankar S. Kim JN. Tetrahedron Lett.  2004,  45:  5043 

7 Cho CS. Lim DK. Zhang JQ. Kim TJ. Shim SC. Tetrahedron Lett.  2004,  45:  5653 

8 Wangelin AJV. Neumann H. Gördes D. Klaus S. Jiao H. Spannenberg A. Krüger T. Wendler C. Thurow K. Stoll N. Beller M. Chem. Eur. J.  2003,  9:  2273 

9 Mohanakrishnan AK. Balamurugan R. Tetrahedron Lett.  2005,  46:  4045 

10 Mohanakrishnan AK. Amaladass P. Tetrahedron Lett.  2005,  46:  4225 

11 All the β-arylcrotonates were prepared by using organozinc addition followed by dehydration using POCl₃. See: Shriner RL. Org React.  1942,  1:  1 

12

General Procedure for the One-Pot Synthesis of Phthalic Acid Derivatives.
The DMF·DMA (1.7 mL, 2.5 mmol) was added to β-phenylethylcrotonate (1.0 g, 1 mmol) at r.t. under N₂. The resulting solution was refluxed at 120 °C for 5 h. After completion of the enamine formation (monitored by TLC), the reaction mixture was cooled to 60 °C, DMAD (0.97 mL, 1.5 mmol) was added and stirred for 30 min. The reaction was quenched by adding 5% ice cold HCl (50 mL), extracted with CH₂Cl₂ (2 × 25 mL). The combined extracts were washed with brine (2 × 20 mL) and dried (Na₂SO₄). Removal of the solvent followed by flash column chromatographic purification (silica gel, hexane-EtOAc, 5:1) afforded 2a as pale-yellow liquid (0.94 g, 52%).
Spectral Data of Selected Compounds. Compound 2b: ¹H NMR (300 MHz, CDCl₃): δ = 1.02 (t, J = 7.1 Hz, 3 H), 2.40 (s, 3 H), 3.93 (s, 3 H), 3.94 (s, 3 H), 4.09 (q, J = 7.1 Hz, 2 H), 7.24 (s, 4 H), 7.51 (d, J = 8.0 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 13.49, 21.16, 52.73, 52.88, 61.71, 127.88, 127.98, 129.11, 129.24, 131.26, 131.96, 134.35, 136.26, 138.17, 144.97, 165.72, 167.42, 168.11. MS (EI): m/z (%) = 356 (100) [M⁺], 325 (52), 311 (42), 279 (20).
Compound 2g: ¹H NMR (400 MHz, CDCl₃): δ = 0.87 (t, J = 7.2 Hz, 3 H), 3.94 (s, 3 H), 3.95 (s, 3 H), 4.02 (q, J = 7.2 Hz, 2 H), 7.45-7.47 (m, 1 H), 7.50-7.55 (m, 2 H), 7.61 (d, J = 8.0 Hz, 1 H), 7.82-7.89 (m, 4 H), 8.08 (d, J = 8.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.45, 52.77, 52.91, 61.77, 125.97, 126.59, 126.63, 127.39, 127.68, 127.89, 128.14, 131.28, 131.40, 131.54, 132.28, 132.79, 133.03, 134.58, 136.64, 144.94, 165.71, 167.36, 168.06. MS (EI): m/z (%) = 392 (100) [M⁺], 347 (16), 315 (25), 202 (32).
Compound 2h: ¹H NMR (500 MHz, CDCl₃): δ = 1.11 (t, J = 7.4 Hz, 3 H), 3.89 (s, 3 H), 3.90 (s, 3 H), 4.17 (q, J = 7.4 Hz, 2 H), 7.04-7.10 (m, 2 H), 7.38 (d, J = 5.1 Hz, 1 H), 7.58 (d, J = 8.0 Hz, 1 H), 7.96 (d, J = 8.0 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 13.74, 52.95, 52.99, 53.10, 62.13, 127.51, 127.63, 128.28, 131.17, 131.62, 132.40, 134.29, 137.06, 139.79, 165.68, 167.35, 167.82. MS (EI): m/z (%) = 348 (100) [M⁺], 303 (61), 257 (58), 186 (26).
Compound 2d′: ¹H NMR (400 MHz, CDCl₃): δ = 1.03 (t, J = 7.2 Hz, 3 H), 3.88 (s, 3 H), 4.09 (q, J = 7.2 Hz, 2 H), 7.18 (d, J = 8.0 Hz, 2 H), 7.30-7.35 (m, 3 H), 8.09 (d, J = 6.8 Hz, 1 H), 8.42 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.74, 52.18, 61.31, 121.64, 128.29, 129.48, 129.56, 130.79, 131.17, 131.40, 131.99, 133.98, 135.01, 138.92, 145.49, 165.95, 167.39. MS (EI): m/z (%) = 318 (100) [M⁺], 287 (18), 273 (85), 186 (21).