Synthesis of the First Thiazolidine-Condensed Five-, Six-, and Seven-Membered Heterocycles via Cyclization of Vinylogous N-Acyliminium Ions

Abstract

Synthesis of new thiazolidine-fused five-, six-, and seven-membered heterocycles through vinylogous N-acyliminium ion-cyclization sequence, involving positions 3 and 4 of the thiazolidine ring, is described. The formation of bicyclic products, arising by generally disfavored 5-endo-trig cyclization initiated by sulfur atom acting as a nucleophile, indicates the preparative value of this method.

Key words

neighboring-group effects - lactams - iminium ions - cyclization - fused-ring systems

References and Notes

• 1a Schultz AG. Pettus L. J. Org. Chem.  1997,  62:  6855 
• 1b Pandey G. Das P. Reddy PY. Eur. J. Org. Chem.  2000,  657 
• 2a Pei X.-F. Greig NH. Flippen-Anderson JL. Bi S. Brossi A. Helv. Chim. Acta  1994,  77:  1412 
• 2b Ishibashi H. Kato I. Takeda Y. Tamura O. Tetrahedron Lett.  2001,  42:  931 
• 3a Fuji K. Kawabata T. Ohmori T. Shang M. Node M. Heterocycles  1998,  47:  951 
• 3b Forns P. Diez A. Rubiralta M. J. Org. Chem.  1996,  61:  7882 
• 4a Sun P. Sun C. Weinreb SM. J. Org. Chem.  2002,  67:  4337 
• 4b Chihab-Eddine A. Daïch A. Jilale A. Decroix B. Tetrahedron Lett.  2001,  42:  573 
• For recent reviews on iminium ion cyclization, see:
• 5a Royer J. Bonin M. Micouin L. Chem. Rev.  2004,  104:  2311 
• 5b Maryanoff BE. Zhang H.-C. Cohen JH. Turchi IJ. Maryanoff CA. Chem. Rev.  2004,  104:  1431 
• 5c Speckamp WN. Moolenaar MJ. Tetrahedron  2000,  56:  3817 
• 6a Hart DJ. J. Org. Chem.  1981,  46:  367 
• 6b Winterfeldt E. Synthesis  1975,  617 
• 6c Padwa A. Kappe CO. Cochran JE. Snyder JP. J. Org. Chem.  1997,  62:  2786 
• 7 Marković R. Baranac M. Steel PJ. Kleinpeter E. Stojanović M. Heterocycles  2005,  65:  2635 
• 8a Marković R. D˛ambaski Z. Baranac M. Tetrahedron  2001,  57:  5833 
• 8b Marković R. Baranac M. D˛ambaski Z. Stojanović M. Steel PJ. Tetrahedron  2003,  59:  7803 
• 9a Pujari HK. Adv. Heterocycl. Chem.  1990,  49:  1 
• 9b Köpper S. Lindner K. Martens J. Tetrahedron  1992,  48:  10277 
• 10a Pinck LA. Hilbert GE. J. Am. Chem. Soc.  1946,  751 
• 10b McKillop A. Ford ME. Tetrahedron  1974,  30:  2467 
• 10c Stetter H. Schwarz M. Hirschhorn A. Chem. Ber.  1959,  92:  1629 
• 11 Geluk HW. Schlatmann JLMA. Tetrahedron  1968,  24:  5361 
• For this type of neighboring-group participation, see:
• 12a Pasto DJ. Serve MP. J. Am. Chem. Soc.  1965,  87:  1515 
• 12b Cheng X.-E. Hui Y.-Z. Gu J.-H. Jiang X.-K. Chem. Commun.  1985,  71 
• 12c Bhatt MV. Rao GV. Rao KS. J. Org. Chem.  1979,  44:  984 
• 12d Irie T. Tanida H. J. Org. Chem.  1980,  45:  1759 
• 12e Holum JR. Jorenby D. Mattison P. J. Org. Chem.  1964,  29:  769 
• 13 Zheng T.-C. Burkart M. Richardson DE. Tetrahedron Lett.  1999,  40:  603 
• 14 Van Maarseveen JH. Scheeren HW. Kruse CG. Tetrahedron  1993,  49:  2325 
• For recent examples of the 5-endo-trig mode ring-closing reaction, see:
• 17a Fuwa H. Sasaki M. Org. Lett.  2007,  9:  3347 
• 17b Kim I. Won HK. Choi J. Lee GH. Tetrahedron  2007,  63:  12954 
• 17c Ray D. Paul S. Brahma S. Ray JK. Tetrahedron Lett.  2007,  48:  8005 
• 17d Bogen S. Goddard J.-P. Fensterbank L. Malacria M. ARKIVOC  2008,  (viii):  126 
• 17e Ichikawa J. Iwai Y. Nadano R. Mori T. Ikeda M. Chem. Asian J.  2008,  3:  393 
• 17f Marchand P. Gulea M. Masson S. Saquet M. Collignon N. Org. Lett.  2000,  2:  3757 
• 17g Bommezijn S. Martin CG. Kennedy AR. Lizos D. Murphy JA. Org. Lett.  2001,  3:  3405 
• 17h Chowdhury MA. Reissig H.-U. Synlett  2006,  2383 
• 17i Clark AJ. Dell CP. McDonagh JM. Geden J. Mawdsley P. Org. Lett.  2003,  5:  2063 
• 17j Jones AD. Redfern AL. Knight DW. Morgan IR. Williams AC. Tetrahedron  2006,  62:  9247 
• 17k Clive DLJ. Yang W. MacDonald AC. Wang Z. Cantin M. J. Org. Chem.  2001,  66:  1996 
• 17l Geyer A. Moser F. Eur. J. Org. Chem.  2000,  1113 
• 18a Baldwin JE. Chem. Commun.  1976,  736 
• 18b Baldwin JE. Thomas RC. Kruse LI. Silberman L. J. Org. Chem.  1977,  42:  3846 
• 19 Chatgilialoglu C. Ferreri C. Guerra M. Timokhin V. Froudakis G. Gimisis T. J. Am. Chem. Soc.  2002,  124:  10765 

15

Typical Procedure for the Synthesis of ( Z )-Ethyl 2-(Tetrahydrothiazolo[4,3- b ][1,3]thiazin-6 (2 H )-ylidene)acetate (9f) The thioester 7f (50.5 mg, 0.17 mmol) was dissolved in dry EtOH (5 mL) and a solution of NaOEt (0.2 M in EtOH, 0.85 mL, 0.17 mmol) was added at r.t. with vigorous stirring. After hydrolysis to thiol, as evidenced by complete consumption of the reactant (ca. 15 min; TLC), the reaction mixture was cooled down to 0 ˚C. Twofold mass excess of NaBH₄ (101 mg, 15-20 mmol equiv) was added, followed by 3 drops of 0.4 M HCl in EtOH. The addition of the same amount of acid was continued in regular 10 min intervals until the end of the reaction (45 min), when the reaction mixture was quenched with 1 M HCl in EtOH. The suspension was stirred for an additional 30 min at 0 ˚C, diluted with H₂O, extracted with CHCl₃, the organic phase separated, dried with Na₂SO₄, and the solvent evaporated under reduced pressure. Purification of a crude product by column chromatography (SiO₂; PE-EtOAc solvent gradient 100:0 → 80:20) afforded the final product 9f as a white solid (27.4 mg, 66%); mp 108-109 ˚C. ^¹H NMR (200 MHz, CDCl₃): δ = 1.27 (3 H, t, J = 7.4 Hz, CH ₃CH₂), 1.65-2.05 (2 H, m, C₃H₂), 2.76-2.83 (1 H, m, C₂H), 2.83 (1 H, dd, J ₁ = 11.8 Hz, J ₂ = 2.0 Hz, C₈H), 3.12 (1 H, ddd, J ₁ = 13.6 Hz, J ₂ = 12.2 Hz, J ₃ = 3.0 Hz, C₂H), 3.27 (1 H, ddd, J ₁ = 14.4 Hz, J ₂ = 12.6 Hz, J ₃ = 2.6 Hz, C₄H), 3.39 (1 H, dd, J ₁ = 11.8 Hz, J ₂ = 7.2 Hz, C₈H), 3.80-3.87 (1 H, m, C₄H), 4.17 (2 H, q, J = 7.4 Hz), 5.05 (1 H, s, C_{6 ′}H), 5.18 (1 H, dd, J ₁ = 7.2 Hz, J ₂ = 2.0, C_8aH) ppm. ^¹³C NMR (50.3 MHz, CDCl₃): δ = 14.6 (CH₃CH₂), 22.0 (C₃), 29.1 (C₂), 33.0 (C₈), 46.8 (C₄), 59.3 (CH₂CH₃), 67.5 (C_8a), 83.5 (C_{6 ′}), 162.3 (C₆), 168.9 (CO₂) ppm. IR: 2977, 2951, 2925, 2897, 1662, 1531, 1459, 1427, 1335, 1276, 1226, 1205, 1177, 1144, 1102, 1043, 1003, 900, 809 cm^-¹. HR MS (CI/TOF): m/z [M + H]⁺ calcd: 246.06170; found: 246.06176 ± 0.24 ppm.

16

Analytical Data of (Z)-Ethyl 2-{7-Methyl-2H-thiazolo[4,3-b]thiazol-5 (3H,7H,7aH)-ylidene}acetate (9c)
Isolated in 37% yield as a mixture of trans- and cis-isomer in a 75:25 ratio.
Compound trans-9c: ^¹H NMR (500 MHz, CDCl₃): δ = 1.26 (3 H, t, J = 7.0 Hz, CH ₃CH₂), 1.49 (3 H, d, J = 6.5 Hz, CH ₃CHS), 3.09-3.12 (1 H, m, CH₂S), 3.15-3.20 (1 H, m, CH₂S), 3.26-3.32 (1 H m, CH₂N), 3.66 (1 H, dq, J ₁ = 6.5 Hz, J ₂ = 5.5 Hz, CHCH₃S), 3.97 (1 H, ddd, J ₁ = 9.0 Hz, J ₂ = 6.0 Hz, J ₃ = 3.0 Hz, CH₂N) 4.16 (2 H, q, J = 7.0 Hz, CH ₂CH₃), 4.89 (1 H, d, J = 5.5 Hz, CHSN), 5.07 (1 H, s, = CH) ppm. ^¹³C NMR (50.3 MHz, CDCl₃): δ = 14.5 (CH₃CH₂), 20.1 (CH₃CHS), 32.0 (CH₂S), 45.1 (CHCH₃S), 50.7 (CH₂N), 59.4 (CH₂CH₃), 76.8 (CHSN), 84.4 (=CH), 163.76 (C=), 168.6 (CO₂) ppm.
Compound cis-9c: ^¹H NMR (500 MHz, CDCl₃): δ = 1.27 (3 H, t, J = 7.0 Hz, CH ₃CH₂), 1.46 (3 H, d, J = 7.0 Hz, CH ₃CHS), 3.05-3.09 (1 H, m, CH₂S), 3.24-3.33 (1 H, m, CH₂S), 3.29-3.41 (1 H, m, CH₂N), 3.89 (1 H, dq, J ₁ = 7.0 Hz, J ₂ = 5.5 Hz, CHCH₃S), 4.00 (1 H, ddd, J ₁ = 9.2 Hz, J ₂ = 5.8 Hz, J ₃ = 3.2 Hz, CH₂N) 4.16 (2 H, q, J = 7.0 Hz, CH₂CH₃), 5.10 (1 H, s, =CH), 5.28 (1 H, d, J = 5.5 Hz, CHSN) ppm. ^¹³C NMR (50.3 MHz, CDCl₃): δ = 14.5 (CH₃CH₂), 17.0 (CH₃CHS), 31.0 (CH₂S), 41.3 (CHCH₃S), 51.0 (CH₂N), 59.4 (CH₂CH₃), 76.8 (CHSN), 84.8 (=CH), 163.8 (C=), 168.6 ppm.