Ph₃P-Mediated Tandem Synthesis of Functionalized Cyclopentadienes from Primary Alkylamines and Acetylenic Esters

Abstract

Dialkyl 4-[alkyl(alkoxycarbonyl)amino]-3-alkoxy-1,3-cyclopentadiene-1,2-dicarboxylates are obtained in good yields via a tandem reaction between triphenylphosphine, primary alkylamines, and acetylenic esters in dichloromethane in the absence of catalyst.

Key words

primary alkylamine - acetylenic ester - 1,3-cyclopentadiene - tandem reaction

References and Notes

• 1 Mukaiyama T. Challenges in Synthetic Organic Chemistry   Clarendon Press; Oxford: 1990. 
• 2 Ho T.-L. Tandem Organic Reactions   John Wiley and Sons; New York: 1992. 
• 3 Ho T.-L. Tactics of Organic Synthesis   John Wiley and Sons; New York: 1994. 
• 4 Serratosa F. Xicart J. Organic Chemistry in Action: The Design of Organic Synthesis   Elsevier; New York: 1996. 
• 5 Smith WA. Bochkov AF. Caple R. Organic Synthesis: The Science behind the Art   RSC; Cambridge / UK: 1998. 
• 6 Yavari I. Khalili G. Mirzaei A. Tetrahedron Lett.  2010,  51:  1190 
• 7 Yavari I. Mirzaei A. Moradi L. Khalili G. Tetrahedron Lett.  2010,  51:  396 
• 8 Yavari I. Souri S. Sirouspour M. Bayat MJ. Synlett  2009,  1921 
• 9 Yavari I. Piltan M. Moradi L. Tetrahedron  2009,  65:  2067 
• 11 Yavari I. Shaabani A. Soleimani H. Nourmohammadian F. Bijanzadeh HR. Magn. Reson. Chem.  1996,  34:  1003 

10

Compounds 4a-g - General Procedure To a stirred solution of amine 2 (2 mmol) and the acetylenic ester (4 mmol) in CH₂Cl₂ (10 mL), was added Ph₃P (0.53 g, 2 mmol) at 0 ˚C, and the mixture was allowed to reach r.t. After completion of the reaction (6-12 h; TLC monitoring, EtOAc-hexane = 1:4), the solvent was evaporated, and the residue was purified by column chromatography (silica gel (230-400 mesh; Merck), hexane-EtOAc = 5:1): pure product.
Dimethyl 4-[Benzyl(methoxycarbonyl)amino]-3-methoxy-1,3-cyclopentadiene-1,2-dicarboxylate (4a) Yellow oil; yield 0.53 g (71%). IR (KBr): ν_max = 1732, 1707, 1625, 1560, 1506, 1451, 1409, 1282, 1248, 1151, 1090, 742, 687 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 3.52 (2 H, s, CH₂), 3.58, 3.76, 3.84, 3.89 (12 H, s, 4 MeO), 5.50 (2 H, s, CH), 6.97 (2 H, d, ^³ J = 7.8 Hz, CH), 7.25-7.32 (3 H, m, CH) ppm. ^¹³C NMR (125.7 MHz, CDCl₃): δ = 29.3 (CH₂), 48.8, 51.8, 52.0, 52.2 (4 MeO), 63.0 (CH₂N), 113.6 (C), 120.1 (C), 121.0 (C), 125.9 (2 CH), 127.4 (CH), 128.7 (2 CH), 136.7 (C), 143.9 (C), 161.0 (COO), 164.9 (COO), 169.5 (COO) ppm. MS: m/z (%) = 376 (7) [M⁺ + 1], 375 (22) [M⁺], 361 (4), 344 (10), 311 (11), 284 (5), 91 (75), 77 (21), 59 (11). Anal. Calcd for C₁₉H₂₁NO₇ (375.37): C, 60.80; H, 5.64; N, 3.73. Found: C, 61.1; H, 5.7; N, 3.7.
Compounds 4h-m - General Procedure To a stirred solution of amine 2 (2 mmol) and the first acetylenic ester (2 mmol) in CH₂Cl₂ (10 mL), was simultaneously added Ph₃P (0.52 g, 2 mmol) and the second acetylenic ester (2 mmol) at 0 ˚C. The mixture was then allowed to reach r.t. After completion of the reaction (6-12 h; TLC monitoring, EtOAc-hexane = 1:4), the solvent was evaporated, and the residue was purified by column chromatography [silica gel (230-400 mesh; Merck), hexane-EtOAc = 5:1]: pure product.
Diethyl 4-[Benzyl(methoxycarbonyl)amino]-3-methoxy-1,3-cyclopentadiene-1,2-dicarboxylate (4h) Pale yellow oil; yield 0.60 g (75%). IR (KBr): ν_max = 1735, 1704, 1629, 1596, 1503, 1452, 1416, 1280, 1247, 1150, 1094, 744, 693 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.26 (3 H, t, ^³ J = 7.1 Hz, Me), 1.38 (3 H, t, ^³ J = 7.1 Hz, Me), 3.52 (2 H, s, CH₂), 3.58, 3.85 (6 H, s, 2 MeO), 4.22 (2 H, q, ^³ J = 7.1 Hz, CH₂O), 4.36 (2 H, q, ^³ J = 7.1 Hz, CH₂O), 5.50 (2 H, s, CH₂N), 6.98 (2 H, d, ^³ J = 7.3 Hz, CH), 7.25 (1 H, t, ^³ J = 7.2 Hz, CH), 7.31 (2 H, t, ^³ J = 7.2 Hz, CH) ppm. ^¹³C NMR (125.7 MHz, CDCl₃): δ = 13.9 (Me), 14.1 (Me), 28.9 (CH₂), 48.7, 52.2 (2 MeO), 60.8, 60.9 (2 OCH₂), 63.0 (CH₂N), 114.0 (C), 120.1 (C), 120.8 (C), 125.9 (2 CH), 127.4 (CH), 128.6 (2 CH), 136.8 (C), 143.7 (C), 160.6 (COO), 164.5 (COO), 169.6 (COO) ppm. MS: m/z (%) = 404 (12) [M⁺ + 1], 403 (28) [M⁺], 389 (4), 372 (6), 325 (13), 312 (5), 91 (75), 77 (25), 73 (16), 59 (12). Anal. Calcd for C₂₁H₂₅NO₇ (403.42): C, 62.52; H, 6.25; N, 3.47. Found: C, 62.4; H, 6.3; N, 3.5.
Dimethyl 4-[Benzyl(ethoxycarbonyl)amino]-3-ethoxy-1,3-cyclopentadiene-1,2-dicarboxylate (4m) Pale yellow oil; yield 0.54 g (67%). IR (KBr): ν_max = 1738, 1714, 1630, 1590, 1513, 1458, 1421, 1291, 1247, 1155, 1099, 745, 690 cm^-¹. ^¹H NMR (500.1 MHz, CDCl₃): δ = 1.19 (3 H, t, ^³ J = 7.1 Hz, Me), 1.30 (3 H, t, ^³ J = 7.1 Hz, Me), 3.49 (2 H, s, CH₂), 3.76, 3.87 (6 H, s, 2 MeO), 4.02 (2 H, q, ^³ J = 7.1 Hz, CH₂O), 4.04 (2 H, q, ^³ J = 7.1 Hz, CH₂O), 5.50 (2 H, s, CH₂N), 6.94 (2 H, d, ^³ J = 7.3 Hz, CH), 7.23 (1 H, t, ^³ J = 7.2 Hz, CH), 7.28 (2 H, t, ^³ J = 7.2 Hz, CH) ppm. ^¹³C NMR (125.7 MHz, CDCl₃): δ = 14.0 (Me), 15.3 (Me), 29.6 (CH₂), 48.8, 51.9 (2 MeO), 52.0, 61.3 (2 OCH₂), 71.5 (CH₂N), 114.5 (C), 121.1 (C), 121.8 (C), 125.9 (2 CH), 127.4 (CH), 128.7 (2 CH), 135.8 (C), 144.7 (C), 161.5 (COO), 163.4 (COO), 168.5 (COO) ppm. MS: m/z (%) = 404 (8) [M⁺ + 1], 403 (17) [M⁺], 389 (4), 372 (6), 325 (11), 91 (70), 77 (22), 73 (12), 59 (9). Anal. Calcd for C₂₁H₂₅NO₇ (403.42): C, 62.52; H, 6.25; N, 3.47. Found: C, 62.7; H, 6.4; N, 3.6.