A Versatile Access to 1-Cyclopropyl-2-aryl-1,3,5-hexatrienes - Domino Heck-Diels-Alder Reactions of 1,3-Dicyclopropyl-1,2-propadiene [1]

Abstract

An efficient three-step synthesis of 1,3-dicyclopropyl-1,2-propadiene (4) (overall yield 68%) starting from dicyclopropyl-acetylene was developed. The allene, when coupled with several aryl iodides and aryl bromides under palladium catalysis in the presence of a reactive dienophile, was found to undergo a domino Heck-Diels-Alder reaction to yield 3-(1′-arylalkenyl)-substituted cyclohexenes 9 in moderate to good yields (36-86%).

allenes - domino reactions - palladium catalysis - cross-coupling reactions - cycloadditions

References

<A NAME="RG30902ST-1A">1a</A>

Part 85 in the series ‘Cyclopropyl Building Blocks for Organic Synthesis’.

<A NAME="RG30902ST-1B">1b</A>

Part 84, see: Belov, V. N.; Savchenko, A. I.; Sokolov, V. V.; Straub, A.; de Meijere, A. Eur. J. Org. Chem. 2003, in press.

<A NAME="RG30902ST-1C">1c</A>

Part 83: Leonov, A.; Heiner, T.; Bes, M. T.; de Meijere, A. Eur. J. Org. Chem. 2003, in press.

<A NAME="RG30902ST-2A">2a</A> Tietze LF. Beifuss U. Angew. Chem., Int. Ed. Engl.  1993,  32:  131 ; Angew. Chem.  1993,  105:  137 

<A NAME="RG30902ST-2B">2b</A> Tietze LF. Chem. Rev.  1996,  96:  115 

<A NAME="RG30902ST-2C">2c</A> de Meijere A. Meyer FE. Angew. Chem., Int. Ed. Engl.  1994,  33: 2379; Angew. Chem. 1994, 106, 2473

<A NAME="RG30902ST-3A">3a</A> Bräse S. de Meijere A. In Metal-catalyzed Cross-coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1998.  p.99 

<A NAME="RG30902ST-3B">3b</A> de Meijere A. Bräse S. J. Organomet. Chem.  1999,  576:  88 

<A NAME="RG30902ST-3C">3c</A> Poli G. Giambastiani G. Heumann A. Tetrahedron  2000,  56:  5959 

<A NAME="RG30902ST-3D">3d</A> Winkler JD. Chem. Rev.  1996,  96:  167 

<A NAME="RG30902ST-4A">4a</A> Grigg R. Mariani E. Sridharan V. Tetrahedron Lett.  2001,  42:  8677 

<A NAME="RG30902ST-4B">4b</A> Copéret C. Ma S. Negishi E.-i. Angew. Chem., Int. Ed. Engl.  1996,  35:  2125 ; Angew. Chem. 1996, 108, 2255

<A NAME="RG30902ST-4C">4c</A> Yufit DS. Kozhushkov SI. Howard JAK. de Meijere A. Acta Cryst.  2002,  B58:  673 

<A NAME="RG30902ST-5A">5a</A> Nüske H. Bräse S. Kozhushkov SI. Noltemeyer M. Es-Sayed M. de Meijere A. Chem.-Eur. J.  2002,  8:  2350 

<A NAME="RG30902ST-5B">5b</A> de Meijere A. Nüske H. Es-Sayed M. Labahn T. Schroen M. Bräse S. Angew. Chem. Int. Ed.  1999,  38:  3669 ; Angew. Chem. 1999, 111, 3881

<A NAME="RG30902ST-6">6</A> Nüske H. Noltemeyer M. de Meijere A. Angew. Chem. Int. Ed.  2001,  40:  3411 ; Angew. Chem.; 2001, 113: 3509

<A NAME="RG30902ST-7">7</A> 1,3-Dicyclopropyl-1,2-propadiene was first detected and characterized by IR, ¹H NMR and mass spectroscopy, among the pyrolysis products from cyclopropylketene dimer: Berkowitz WF. Ozorio AA. J. Org. Chem.  1975,  40:  527 

<A NAME="RG30902ST-8A">8a</A> Scott LT. Cooney MJ. Otte C. Puls C. Haumann T. Boese R. Smith AB. Carroll PJ. de Meijere A. J. Am. Chem. Soc.  1994,  116:  10275 

<A NAME="RG30902ST-8B">8b</A> Militzer H.-C. Schömenauer S. Otte C. Puls C. Hain J. Bräse S. de Meijere A. Synthesis  1993,  10:  998 

<A NAME="RG30902ST-8C">8c</A> Köbrich G. Merkel D. Thiem K.-W. Chem. Ber.  1972,  105:  1683 

<A NAME="RG30902ST-8D">8d</A> Köbrich G. Merkel D. Angew. Chem., Int. Ed. Engl.  1970,  9:  169 ; Angew. Chem. 1970, 82, 257

<A NAME="RG30902ST-9">9</A> Kazimirchik IV. Lukin KA. Bebikh GF. Zefirov NS. J. Org. Chem. USSR  1983,  19:  2209 ; Zh. Org. Khim. 1983, 19, 2523

<A NAME="RG30902ST-10">10</A> Sato F. Ishikawa H. Sato M. Tetrahedron Lett.  1981,  22:  85 

<A NAME="RG30902ST-11">11</A> Best yields of 3 were achieved according to the most recently published protocol employing powdered sodium hydroxide: Xu L. Brinker UH. In Synthetic Organic Sonochemistry   Lucke JL. Plenum Press; New York: 1998.  p.344 

<A NAME="RG30902ST-12">12</A>

Dimethyl 3-[(2′-Cyclopropyl-1′-phenyl)ethenyl]cyclo-hex-4-en-( E )-1,2-dicarboxylate ( 5a). Typical Procedure: A solution of 11.2 mg (50.0 µmol, 5 mol%) of palladium(II) acetate and 39.3 mg (150 µmol) of triphenylphosphine in 1 mL of anhyd DMF in a 5 mL Pyrex-screw-cap bottle is flushed with nitrogen for 10 min. A mixture of 120 mg
(1.00 mol) of 1,3-dicyclopropyl-1,2-propadiene, 245 mg (1.20 mmol) of phenyl iodide, 202 mg (2.00 mmol) of triethylamine and 288 mg (2.00 mmol) of dimethyl maleate are added and the mixture is stirred under nitrogen in the capped bottle at 100 °C for 24 h. The reaction is quenched by addition of 10 mL of water, and the mixture is extracted with diethyl ether (4 × 10 mL). The combined organic layers are washed with water (3 × 25 mL) and brine (25 mL). The solution is dried (MgSO₄), the solvent removed, and the residue purified by chromatography on 60 g of silica gel [pentane-diethyl ether (10:1), R _f = 0.10] to yield 293 mg (86%) of 5a. IR (KBr): ν = 2982, 2873, 1746, 1492, 1383, 1249, 1125, 1077, 953, 845, 763, 702 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 0.21-0.27 (m, 2 H, cPr-H), 0.56 (ddd, ³ J = 8.2, 2.4 Hz, ² J = 0.6 Hz, 2 H, cPr-H), 1.17 (m, 1 H, cPr-H), 2.10 (m, 1 H, 6-H), 2.27 (m, 1 H, 6-H), 2.69 (dd, ³ J = 10.9, 10.1 Hz, 1 H, 2-H), 2.94 (dt, ³ J = 10.9, 5.4 Hz, 1 H, 1-H), 3.37 (ddd, ³ J = 10.1, 3.9 Hz, ⁴ J = 2.0 Hz, 1 H, 3-H), 3.57 (s, 3 H, OCH₃), 3.60 (s, 3 H, OCH₃), 4.81 (d, ³ J = 9.9 Hz, 1 H, 2′-H), 5.64 (m, 2 H, 4-H, 5-H), 7.14-7.32 (m, 5 H, Ph-H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 7.3 (CH₂, cPr-C), 11.1 (CH, cPr-C), 27.2 (CH₂, C-6), 42.1 (CH, C-1), 46.6 (CH, C-2), 48.5 (CH, C-3), 51.5 (CH₃, OCH₃), 51.9 (CH₃, OCH₃), 124.6 (CH, C-5), 126.7 (CH, Ph-C), 127.8 (CH, Ph-C), 129.6 (CH, C-4), 129.7 (CH, Ph-C), 135.2 (CH, C-2′), 138.6 (C _quat, Ph-C), 139.2 (C _quat, C-1′), 174.4 (C _quat, COO), 175.1 (C _quat, COO). MS (EI, 70 eV): m/z (%) = 341/340 (8/38) [M⁺], 309(20), 280(100), 249(39), 221(61), 205(33), 193(28), 167(29), 143(70), 128(34), 115(24), 91(43), 77(8), 59(12), 41(4). Calcd. for C₂₁H₂₄O₄ (340.4): C, 74.09; H, 7.11. Found: C, 74.34; H, 6.94.

<A NAME="RG30902ST-13A">13a</A>

Stepwise proceeding Diels-Alder reactions have been predicted according to computations and also been observed experimentally.

<A NAME="RG30902ST-13B">13b</A> Dewar MJS. Olivella S. Stewart JJP. J. Am. Chem. Soc.  1986,  108:  5771 

<A NAME="RG30902ST-13C">13c</A> Goldstein E. Beno B. Houk KN. J. Am. Chem. Soc.  1996,  118:  6036 

<A NAME="RG30902ST-14">14</A> The isomerization of dimethyl maleate to dimethyl fumarate under Heck coupling conditions has previously been documented: Cortese NA. Ziegler CB. Hrnjez BJ. Heck RF. J. Org. Chem.  1978,  43:  2952 

<A NAME="RG30902ST-15">15</A>

A control experiment which was carried out with the isolated hexatriene 7 and dimethyl maleate in 5 mL DMSO at 100 °C for 18 h in the absence of any base and palladium catalyst, gave the same product 5a as a mixture of diastereoisomers (2.3:1) in 36% yield.

<A NAME="RG30902ST-16">16</A>

All new compounds were fully characterized by spectroscopic methods (¹H NMR, ¹³C NMR, IR, MS) and bulk purities were established for most of them by elemental analysis.

<A NAME="RG30902ST-17">17</A>

Typical Two-step Procedure: A solution of 11.2 mg (50.0 µmol, 5 mol%) of palladium(II) acetate and 39.3 mg (150 µmol) of triphenylphosphine in 1 mL of anhyd DMF in a 5 mL Pyrex-screw-cap bottle is flushed with nitrogen for 10 min. 120 mg (1.00 mol) of 1,3-dicyclopropyl-1,2-propadiene, 1.20 mmol of the aryl iodide and 202 mg (2.00 mmol) of triethylamine are added, and the mixture is stirred at 80 °C for 5 h. Then 2 mmol of the dienophile is added and the mixture is stirred at 100 °C for 18 h. The reaction is quenched by addition of 10 mL of water, and the mixture extracted with diethyl ether (3 × 10 mL). The combined organic layers are washed with water (2 × 25 mL) and brine (25 mL). After drying (MgSO₄), the solvent is removed and the residue purified by chromatography.

The facile oxidation of Diels-Alder adducts with p-benzoquinone is well documented:

<A NAME="RG30902ST-18A">18a</A> Ansell MF. Nash BW. Wilson DA. J. Chem. Soc.  1963,  3006 

<A NAME="RG30902ST-18B">18b</A> Willmore ND. Longbin L. Katz TJ. Angew. Chem., Int. Ed. Engl.  1992,  31:  1093 ; Angew. Chem. 1992, 104, 1081