Download PDF
Synlett 2010(14): 2063-2066  
DOI: 10.1055/s-0030-1258513
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Simple Preparative Synthesis of Epoxy[1,3]oxazino(or oxazolo)[2,3-a]-isoindoles and Their Thia Analogues via IMDAF

Fedor I. Zubkov*, Timur R. Galeev, Eugeniya V. Nikitina, Irina V. Lazenkova, Vladimir P. Zaytsev, Alexey V. Varlamov
Organic Chemistry Department, Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation
Fax: +7(495)9522644; e-Mail: fzubkov@sci.pfu.edu.ru;
Further Information

Publication History

Received 7 May 2010
Publication Date:
22 July 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

Azomethines, easily prepared from 5-(R)-furfurals and 1,3- or 1,2-amino alcohols (aminothiols), react under mild conditions with maleic anhydride affording 8,10a-epoxy[1,3]oxa(thia)-zino[2,3-a]isoindole-7- and 7,9a-epoxy[1,3]oxa(thia)zolo[2,3-a]isoindole-6-carboxylic acids. The reaction proceeds through initial N-acylation with subsequent intramolecular exo-Diels-Alder cycloaddition and stereoselectively leads to the exo adducts. The ‘one-pot’ synthetic protocol is also presented.

Key words

furan - Diels-Alder reaction - stereoselective synthesis - [1,3]oxazolo[2,3-a]isoindoles - [1,3]oxazino[2,3-a]isoindoles - IMDAF

    References and Notes

  • 1 For IMDAF review, see: Zubkov FI. Nikitina EV. Varlamov AV. Russ. Chem. Rev. (Engl. Transl.)  2005,  74:  639 
    CrossrefGoogle Scholar
  • 2 Zubkov FI. Nikitina EV. Turchin KF. Aleksandrov GG. Safronova AA. Borisov RS. Varlamov AV.
    J. Org. Chem.  2004,  69:  432 
    CrossrefGoogle Scholar
  • 3a Zubkov FI. Boltukhina EV. Turchin KF. Borisov RS. Varlamov AV. Tetrahedron  2005,  61:  4099 
    Google Scholar
  • 3b Boltukhina EV. Zubkov FI. Nikitina EV. Varlamov AV. Synthesis  2005,  1859 
    Google Scholar
  • 3c Kouznetsov VV. Cruz UM. Zubkov FI. Nikitina EV. Synthesis  2007,  375 
    Google Scholar
  • 4a Zubkov FI. Boltukhina EV. Turchin KF. Varlamov AV. Tetrahedron  2004,  60:  8455 
    Google Scholar
  • 4b Varlamov AV. Boltukhina EV. Zubkov FI. Nikitina EV. Turchin KF. J. Heterocycl. Chem.  2006,  43:  1479 
    Google Scholar
  • 5 Zubkov FI. Ershova JD. Orlova AA. Zaytsev VP. Nikitina EV. Peregudov AS. Gurbanov AV. Borisov RS. Khrustalev VN. Maharramov AM. Varlamov AV. Tetrahedron  2009,  65:  3789 
    CrossrefGoogle Scholar
  • 6a Jung ME. Street LJ. J. Am. Chem. Soc.  1984,  106:  8327 
    Google Scholar
  • 6b Jung ME. Street LJ. Tetrahedron Lett.  1985,  26:  3639 
    Google Scholar
  • 6c Andrés C. Nieto J. Pedrosa R. Vicente M. J. Org. Chem.  1998,  63:  8570 
    Google Scholar
  • 6d Andrés C. García-Valverde M. Nieto J. Pedrosa R. J. Org. Chem.  1999,  64:  5230 
    Google Scholar
  • 6e Pedrosa R. Andrés C. Nieto J. J. Org. Chem.  2000,  65:  831 
    Google Scholar
  • 6f Kharitonov YuV. Shults EE. Shakirov MM. Tolstikov GA. Russ. J. Org. Chem.  2009,  45:  637 
    Google Scholar
  • 7a Daasch LW. Hanninen UE. J. Am. Chem. Soc.  1950,  72:  3673 
    Google Scholar
  • 7b Belen’kii LI. Cheskis MA. Ryashentseva MA. Chem. Heterocycl. Compd. (Engl. Transl.)  1986,  22:  650 
    Google Scholar
  • 7c Fülöp F. Sillanpää R. Dahlqvist M. Pihlaja K. Vainiotalo P. Heterocycles  1994,  37:  1093 
    Google Scholar
  • 8a Fülöp F. Pihlaja K. Mattinen J. Bernáth G. J. Org. Chem.  1987,  52:  3821 
    Google Scholar
  • 8b Fülöp F. Pihlaja K. Mattinen J. Bernáth G. Tetrahedron  1988,  43:  1863 
    Google Scholar
  • 9a Eliel EL. Roy J. J. Org. Chem.  1965,  30:  3092 
    Google Scholar
  • 9b Oliver GL. Dann JR. Gates JW. J. Am. Chem. Soc.  1958,  80:  702 
    Google Scholar
10

Synthesis of Epoxy[1,3]oxazino[2,3- a ]isoindole-7-carboxylic acids (3a-f): Typical Procedure by Way of Example (6a R *,7 S *,8 R *,10a S *,10b R *)-8-Bromo-6-oxo-3,4,6,6a,7,8-hexahydro-2 H -8,10a-epoxy[1,3]oxazino[2,3- a ]isoindole-7-carboxylic acid (3Ac) and (6a R *,7 S *,8 R *,10a S *,10b S *)-8-Bromo-6-oxo-3,4,6,6a,7,8-hexahydro-2 H -8,10a-epoxy[1,3]oxazino[2,3- a ]isoindole-7-carboxylic acid (3Bc) To a stirred solution of 5-bromofurfural (5.0 g, 29 mmol) and 3-aminopropanol (2.2 mL, 29 mmol) in CH2Cl2 (50 mL) anhyd MgSO4 powder (7 g, 60 mmol) was added at r.t. After ca. 24 h, the MgSO4 was filtered off and the CH2Cl2 evaporated. The residue was diluted with acetone (30 mL), and then a solution of maleic anhydride (3.13 g, 32 mmol) in acetone (20 mL) was added. The resulting yellow transparent mixture was kept for ca. 4 h at 24 ˚C. Then the yellow precipitate was filtered off, washed twice with acetone (2 ¥ 20 mL), and dried in air to give the title acids 3c as a white powder (3.9 g, 41% yield). Isomeric ratio 3Ac/3Bc = 5:1; mp (for isomeric mixture) 208-209 ˚C. IR (KBr): νmax = 1670 (CON), 1751 (COOH), 3136 (COOH) cm-¹. ¹H NMR (600 MHz, DMSO-d 6, 25 ˚C): δ (major isomer 3Ac): 12.60 (br s, 1 H, CO2H), 6.73 and 6.55 (2 d, ³ J 9,10 = 5.5 Hz, 1 H and 1 H, 9-H and 10-H), 5.18 (s, 1 H, 10b-H), 4.07 (dd, ² J 2A,2B = 11.7, ³ J 2A,3eqv = 4.1 Hz, 1 H, 2-HA), 3.90-3.86 (m, 2 H, 4-HA and 2-HB), 3.09 (dd, ² J 4B,4A = 12.4, ³ J 4B,3eqv = 3.4 Hz, 1 H, 4-HB), 2.98 and 2.96 (2 d, ³ J 6a,7 = 8.9 Hz, 1 H and 1 H, 7-H and 6a-H), 1.62-1.55 (m, 1 H, 3-HA), 1.46-1.48 (m, 1 H, 3-HB) ppm; δ (minor isomer 3Bc): 12.60 (br s, 1 H, CO2H), 6.76 and 6.48 (2 d, ³ J 9,10 = 5.5 Hz, 1 H and 1 H, 9-H and 10-H), 5.37 (s, 1 H, 10b-H), 4.07 (dd, ² J 2A,2B = 11.7, ³ J 2A,3eqv = 4.1 Hz, 1 H, 2-HA), 3.85-3.82 (m, 2 H, 4-HA and 2-HB), 3.66 (dd, ² J 4B,4A = 11.7, ³ J 4B,3 = 2.0 Hz, 1 H, 4-HB), 2.98 and 2.96 (2 d, ³ J 6a,7 = 8.9 Hz, 1 H and 1 H, 7-H and 6a-H), 1.62-1.55 (m, 1 H, 3-HA), 1.46-1.48 (m, 1 H, 3-HB) ppm. ¹³C NMR (100.6 MHz, D2O/NaOD, 25 ˚C): δ (major isomer 3Ac): 173.1 and 171.6 (CO2H and 6-C), 138.6 (10-C), 132.4 (9-C), 86.2 and 81.2 (10a-C and 8-C), 83.7 (10b-C), 66.0 (2-C), 51.4 (br s, 7-C), 51.1 (6a-C), 37.0 (4-C), 22.7 (3-C) ppm. EI-MS (70 eV): m/z (%) = 331 (1) [M+, for Br8¹], 329 (1), 303 (3), 301 (5), 286 (7), 285 (7), 284 (7), 250 (10), 232 (25), 230 (25), 201 (11), 199 (11), 175 (13), 173 (11), 137 (18), 199 (12), 86 (100), 85 (18), 65 (15), 56 (24), 41 (18), 39 (19). Anal. Calcd for C12H12BrNO5 (328.99): C, 43.66; H, 3.66; N, 4.24. Found: C, 43.51; H, 3.53; N, 4.16.

11

‘One-Pot’ Synthesis of (5a R* ,6 S* ,9a S* ,9b R* )-5-Oxo-2,3,5,5a,6,7-hexahydro-7,9a-epoxy[1,3]thiazolo[2,3- a ]-isoindole-6-carboxylic acid (5a)
Freshly distilled furfural (1.8 mL, 21.7 mmol) was added in one portion at r.t. to a stirred solution of 2-aminoethanethiol hydrochloride (2.47 g, 21.7 mmol) and Et3N (3.0 mL, 21.7 mmol) in CHCl3 (15 mL). The mixture was stirred for 30 min then cooled to 0 ˚C, and a solution of maleic anhydride
(2.13 g, 21.7 mmol) in CHCl3 (10 mL) was added at this temperature. The mixture was warmed to r.t. and stirred overnight. The precipitate formed was collected by filtration and dried affording compound 5a (2.70 g, 49%) as a white solid; mp 155-156 ˚C(decomp). IR: νmax = 1742 (COOH), 1678 (NC=O) cm-¹. ¹H NMR (400 MHz, DMSO-d 6, 27 ˚C): δ = 6.57 (d, ³ J 8,9 = 5.6 Hz, 1 H, 9-H), 6.48 (dd, ³ J 8,9 = 5.6 Hz, ³ J 7,8 = 1.8 Hz, 1 H, 8-H), 5.66 (s, 1 H, 9b-H), 4.99 (d, ³ J 7,8 = 1.8 Hz, 1 H, 7-H), 4.07 (ddd, ² J = 11.2 Hz, ³ J = 5.6 Hz, ³ J = 2.5 Hz, 1 H, 2-HA), 3.18 (d, J 5a endo ,6 endo  = 8.7 Hz, 1 H, 6-H endo ), 3.09-2.92 (m, 2 H, 2-HB and 3-HA), 2.75-2.68 (m, 1 H, 3-HB), 2.49 (d, ³ J 5a endo ,6 endo  = 8.7 Hz, 1 H, 5a-H endo ) ppm. ¹³C NMR (100.6 MHz, DMSO-d 6, 27 ˚C): δ = 172.6 and 170.3 (5-C and CO2H), 137.7 (9-C), 133.8 (8-C), 92.1 (9a-C), 80.4 (7-C), 63.6 (9b-C), 52.5 and 45.7 (5a-C and
6-C), 44.9 (3-C), 31.9 (2-C) ppm. MS-EI (70 eV): m/z (%) = 253 (10) [M+], 209 (6), 156 (9), 155 (51), 154 (62), 127 (13), 122 (14), 111 (23), 108 (94), 99 (24), 96 (41), 88 (10), 85 (44), 80 (35), 71 (11), 68 (17), 61 (17), 60 (46), 56 (20), 55 (100), 45 (48), 43 (67). Anal. Calcd for C11H11NO4S (253.04): C, 52.16; H, 4.38; N, 5.53; S, 12.66. Found: C, 52.39; H, 4.47; N, 5.43; S, 12.31.