Stereoselective or Exclusive Synthesis of Ethyl (Z)-2-(2-Substituted-thiazol-4-yl)pent-2-enoates from Ethyl (E/Z)-2-(2-Bromoacetyl)pent-2-enoate

Abstract

A stereoselective or exclusive approach to a series of ethyl (Z)-2-(2-substituted-thiazol-4-yl)pent-2-enoates from ethyl (E/Z)-2-(2-bromoacetyl)pent-2-enoate and thioureas or thioamides was reported in good yields. This approach involves a quaternary carbon stereocontrolled cis-configuration formation, and opportunely blocking a potential E/Z isomerization. The practical applicability was highlighted by the synthesis of (Z)-2-(2-tert-butoxycarbonylaminothiazol-4-yl)pent-2-enoic acid, a commercially important side-chain material of cefcapene pivoxil, in a two-step procedure.

Key words

thiazoles - stereocontrolled reaction - E/Z isomerization - antibiotic - cefcapene pivoxil

• References and Notes

• 1a Jagodzinski TS. Chem. Rev. 2003; 103: 197
• 1b Dondoni A, Marra A. Chem. Rev. 2004; 104: 2557
• 1c Li J.-J, Corey EJ. Name Reactions in Heterocyclic Chemistry . John Wiley and Sons; Hoboken: 2005: 275
• 1d Lafontaine JA, Day RF, Dibrino J, Hadcock JR, Hargrove DM, Linhares M, Martin KA, Maurer TS, Nardone NA, Tess DA, DaSilva-Jardine P. Bioorg. Med. Chem. Lett. 2007; 17: 5245
• 1e Wang W.-L, Chai SC, Huang M, He H.-Z, Hurley TD, Ye Q.-Z. J. Med. Chem. 2008; 51: 6110
• 1f Gaumont A.-C, Gulea M, Levillain J. Chem. Rev. 2009; 109: 1371
• 1g Quin LD, Tyrell JA. Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals. John Wiley and Sons; Hoboken: 2010: 228
• 2a Miyamoto K, Nishi Y, Ochiai M. Angew. Chem. Int. Ed. 2005; 44: 6896
• 2b Das B, Reddy VS, Ramu R. J. Mol. Catal. A: Chem. 2006; 252: 235
• 2c Potewar TM, Ingale SA, Srinivasan KV. Tetrahedron 2007; 63: 11066
• 2d Zhu D, Chen J, Wu D, Liu M, Ding J, Wu H. J. Chem. Res. 2009; 84
• 2e Kumar D, Kumar NM, Patel G, Gupta S, Varma RS. Tetrahedron Lett. 2011; 52: 1983
• 3a Yamanaka H, Kawabata K, Miyai K, Takasugi H, Kamimura T, Mine Y, Takaya T. J. Antibiotics 1986; 39: 101
• 3b Jursic B, Sunko DE, Ladika M. Tetrahedron 1987; 43: 4367
• 3c Nishide K, Yamamura M, Yamazaki M, Kobori T, Tunemoto D, Kondo K, Sato K. Chem. Pharm. Bull. 1988; 36: 2346
• 3d Yamada H, Ueda S, Mutoh M, Nagata H, Nouda H, Fukasawa M, Okuda T. J. Antibiotics 1990; 43: 578
• 3e Salomon CJ, Mata EG, Mascaretti OA. Tetrahedron Lett. 1991; 32: 4239
• 3f Yamamoto H, Eikyu Y, Okuda S, Kawabata K, Takasugi H, Tanaka H, Matsumoto S, Matsumoto Y, Tawara S. Bioorg. Med. Chem. 2002; 10: 1535
• 4a Ishikura K, Kubota T, Minami K, Hamashima Y, Nakashimizu H, Motokawa K, Yoshida T. J. Antibiotics 1994; 47: 453
• 4b Tanaka M, Matsuda K. JP 05213968A, 1994 ; Chem. Abstr. 1994, 120, 134147
• 4c Matsunaga T, Hirota Y, Iwasaki F. JP 2002030078A, 2002 ; Chem. Abstr. 2002, 136, 134755
• 4d Desphande PB, Sahoo PK, Sharma HC, Nayal SS. IN 194929A1, 2006 ; Chem. Abstr. 2006, 146, 62701
• 4e Sahoo PK, Sreedhar G, Kamma R, Senthilkumar UP. P. IN 2006CH02154A, 2008 ; Chem. Abstr. 2008, 150, 329475
• 4f Senthilkumar UP, Sreedhar G, Kamma R. IN 2007CH00299A, 2008 ; Chem. Abstr. 2008, 150, 329477
• 4g Gedi S, Ramakrishna K, Udayampalayam PS. WO 2008155615A2, 2008 ; Chem. Abstr. 2008, 150, 77403
• 5 Ishikura K, Kubota T, Minami K, Hamashima Y, Nakashimizu H, Motokawa K, Kimura Y, Miwa H, Yoshida T. J. Antibiotics 1994; 47: 466
• 6 Jiang J.-A, Zhai J.-J, Yu X.-H, Teng X, Ji Y.-F. Synthesis 2012; 44: 207
• 7 Kubota T, Kume M. EP 0467647, 1992 ; Chem. Abstr. 1992, 116, 235340
• 8a Bhatia SH, Buckley DM, Mccabe RW, Avent A, Brown RG, Hitchcock PB. J. Chem. Soc., Perkin Trans. 1 1998; 569
• 8b Anselmi E, Blazejewski J.-C, Wakselman C. J. Fluorine Chem. 2001; 107: 315
• 8c Antonioletti R, Bovicelli P, Malancona S. Tetrahedron 2002; 58: 589
• 9 ¹H NMR analysis indicated the obtained (E/Z)-2 in a 1.0:1.4 ratio under the reaction temperature of –30 °C.

It was shown that the reaction could be immediately stopped by acid-binding agent. The reaction pathway was commonly considered via a hydroxythiazoline intermediate. For the hydroxythiazoline intermediates and their acid-promoted dehydrations in Hantzsch thiazole synthesis, see:
• 10a Lepeshkin AY, Turchin KF, Sedov AL, Velezheva VS. Russ. Chem. Bull., Int. Ed. 2007; 56: 1441
• 10b Lepeshkin AY, Turchin KF, Galpern EG, Stankevich IV, Lyssenko KA, Velezheva VS. Russ. Chem. Bull., Int. Ed. 2007; 56: 1447
• 11 General Procedure for the Synthesis of 4 and 5 The material (E/Z)-2 (1.25 g, 5.0 mmol) were first dissolved in CH₂Cl₂ (15 mL). To the solution was added a solution of 3 (5.0 mmol) in DMF (15 mL) at 0 °C, and then the mixture was stirred at the same temperature for the specified reaction time (t, see text). Thereafter, aq NaHCO₃ (8%, 20 mL) was rapidly added to the mixture. The organic layer was separated, and the aq phase was extracted with CH₂Cl₂ (2 × 25 mL). The combined organic phase was washed with sat. brine (60 mL), dried over anhyd Na₂SO₄. The filtrate was concentrated to give the crude product, which was purified by column chromatography to give 4 and 5 in corresponding yields. Analytical Data for Representative Compounds 4a and 5a Compound 4a: yellow solid, mp 74–76 °C, 0.53 g (47%, neutralizing treatment at 30 min), 0.48 g (42%, t = 2 h). ¹H NMR (400 MHz, CDCl₃): δ = 1.07 (t, J = 7.6 Hz, 3 H), 1.34 (t, J = 7.2 Hz, 3 H), 2.35 (quint, J = 7.6 Hz, 2 H), 4.30 (q, J = 7.2 Hz, 2 H), 5.26 (br s, 2 H), 6.50 (s, 1 H), 6.69 (t, J = 7.6 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 13.8, 14.3, 23.3, 60.8, 104.9, 128.2, 140.6, 147.2, 166.9, 167.6 ppm. ESI-HRMS: m/z [M + H⁺] calcd for C₁₀H₁₅N₂O₂S: 227.0854; found: 227.0854. Compound 5a: yellow solid, mp 107–109 °C, 0.32 g (28%, neutralizing treatment at 30 min), 0.41 g (36%, t = 2 h). ¹H NMR (400 MHz, CDCl₃): δ = 1.04 (t, J = 7.6 Hz, 3 H), 1.27 (t, J = 7.2 Hz, 3 H), 2.31 (quint, J = 7.6 Hz, 2 H), 4.21 (q, J = 7.2 Hz, 2 H), 5.22 (br s, 2 H), 6.42 (s, 1 H), 6.98 (t, J = 7.6 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 13.4, 14.2, 23.2, 60.9, 108.0, 127.7, 145.0, 148.4, 166.7, 166.8 ppm. ESI-HRMS: m/z [M + H⁺] calcd for C₁₀H₁₅N₂O₂S: 227.0854; found: 227.0854.
• 12 The configurations of all compounds 4 and 5 were determined by ¹H-¹H NOESY except 4b, 4c, and 5c for their unstability.
• 13a Arakawa K, Miyasaka T, Ohtsuka H. Chem. Pharm. Bull. 1972; 20: 1041
• 13b Challacombe K, Plackett SJ, Meakins GD. Tetrahedron Lett. 1987; 28: 5767
• 13c Qiao Q, So S.-S, Goodnow RA. Jr. Org. Lett. 2001; 3: 3655
• 13d Ochiai M, Nishi Y, Hashimoto S, Tsuchimoto Y, Chen D.-W. J. Org. Chem. 2003; 68: 7887
• 13e Yavari I, Sayyed-Alangi SZ, Hajinasiri R, Sajjadi-Ghotbabadi H. Monatsh. Chem. 2009; 140: 209
• 14 Preparation Procedure for the New Route to 6 Firstly, the material (E/Z)-2 (2.49 g, 10.0 mmol) were dissolved in CH₂Cl₂ (20 mL). To the solution was added a solution of N-tert-butoxycarbonylthiourea (3e, 1.76 g, 10.0 mmol) in DMF (20 mL) at 0 °C, and then stirred for 30 min at 0 °C. Then, aq NaHCO₃ (8%, 40 mL) was rapidly added to the mixture. The organic layer was separated, and the aqueous phase was extracted with CH₂Cl₂ (2 × 50 mL). The combined organic phase was washed with sat. brine (100 mL), and dried over anhyd Na₂SO₄. The filtrate was concentrated to afford the crude product, which was purified by column chromatography on silica gel (EtOAc–PE, 1:25) to give 4e and 5e. Analytical Data for Compounds 4e and 5e Compound 4e: pale yellow oil; yield: 2.77 g (85%). ¹H NMR (400 MHz, CDCl₃): δ = 1.09 (t, J = 7.6 Hz, 3 H), 1.34 (t, J = 7.2 Hz, 3 H), 1.49 (s, 9 H), 2.41 (quint, J = 7.6 Hz, 2 H), 4.32 (q, J = 7.2 Hz, 2 H), 6.75 (t, J = 7.6 Hz, 1 H), 6.89 (s, 1 H), 9.06 (br s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 13.7, 14.3, 23.3, 28.1 (3 C), 60.8, 82.9 (w), 108.8, 127.8, 141.5, 146.1, 151.9 (w) 159.3, 167.3 ppm. ESI-HRMS: m/z [M + H⁺] calcd for C₁₅H₂₃N₂O₄S: 327.1379; found: 327.1373. Compound 5e: pale yellow solid; mp 69–71 °C; yield: 0.10 g (3%). ¹H NMR (400 MHz, CDCl₃): δ = 1.02 (t, J = 7.6 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.51 (s, 9 H), 2.30 (quint, J = 7.6 Hz, 2 H), 4.19 (q, J = 7.2 Hz, 2 H), 6.84 (s, 1 H), 7.04 (t, J = 7.6 Hz, 1 H), 8.87 (br s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 13.3, 14.2, 23.1, 28.1 (3 C), 60.9, 82.6 (w), 112.4, 127.3, 143.9, 148.7, 151.9 (w), 158.6, 166.6 ppm. ESI-HRMS: m/z [M + H⁺] calcd for C₁₅H₂₃N₂O₄S: 327.1379; found: 327.1381; m/z [M + Na⁺] calcd for C₁₅H₂₂N₂NaO₄S: 349.1198; found: 349.1194. Then, to a solution of 4e (2.61 g, 8.0 mmol) obtained above in 2-PrOH (9 mL) was added aq NaOH (7%, 15 mL), and then stirred for 1.5 h at 65 °C. The mixture was adjusted to pH 3–4 with concd HCl (36.5%, ca. 3 mL), stirred for 1 h at r.t., and then filtered. The filter cake was washed with H₂O (20 mL) and dried in vacuo at 50 °C for 10 h to give 6 (2.17 g, 91%). Analytical Data for Compound 6 White solid; mp 167–169 °C; yield: 2.17 g (91%). ¹H NMR (400 MHz, CDCl₃): δ = 1.11 (t, J = 7.6 Hz, 3 H), 1.55 (s, 9 H), 2.67 (quint, J = 7.6 Hz, 2 H), 6.72 (t, J = 7.6 Hz, 1 H), 6.95 (s, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 13.6, 23.6, 28.1 (3 C), 82.7, 109.2, 126.2, 145.7, 146.9, 152.4, 160.9, 170.9 ppm. ESI-HRMS: m/z [M + H⁺] calcd for C₁₃H₁₉N₂O₄S: 299.1066; found: 299.1066.