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Synlett 2010(10): 1533-1535  
DOI: 10.1055/s-0029-1220068
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Chromeno[3,4-b]pyrrol-4(3H)-ones by Cyclocondensation of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with 4-Chloro-3-nitrocoumarin

Olumide Fatunsina, Viktor O. Iaroshenko*a,b, Sergii Dudkina, Mohanad Shkoora, Dmitro Volochnyukb,c, Ashot Gevorgyana, Peter Langer*a,d
a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax: +49(381)4986412; e-Mail: iva108@googlemail.com; e-Mail: peter.langer@uni-rostock.de;
b National Taras Shevchenko University, 62 Volodymyrska st., Kyiv-33, 01033, Ukraine
c Enamine Ltd., 23 A. Matrosova st., 01103 Kyiv, Ukraine
d Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
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Publication History

Received 4 March 2010
Publication Date:
25 May 2010 (online)

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Abstract

The reaction of 4-chloro-3-nitrocoumarin with 1,3-bis(silyloxy)buta-1,3-dienes and subsequent reductive cyclization provides a convenient synthesis of a variety of chromeno[3,4-b]pyrrol-4(3H)-ones.

Key words

cyclization - coumarin - heterocycles - silyl enol ethers - pyrroles

    References and Notes

  • 1a Kennedy RO. Thorenes RD. Coumarins: Biology, Applications, Mode of Action   Wiley; Chichester: 1997. 
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  • For reviews, see:
  • 1b Yu DL. Suzuki M. Xie L. Morris-Natschke SL. Lee KH. Med. Res. Rev.  2003,  23:  322 
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  • 1c Fylaktakidou KC. Hadjipavlou-Litina DJ. Litines KE. Nicolaides DN. Curr. Pharm. Res.  2004,  10:  3813 
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  • 1d Borges F. Roleira F. Mihazes N. Santana L. Uriarte E. Curr. Med. Chem.  2005,  12:  887 
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  • 2 Chen L. Xu MH. Adv. Synth. Catal.  2009,  351:  2005 ; and references 2-5 cited therein
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  • 3 For a review, see: Langer P. Synthesis  2002,  441 
    Article in Thieme ConnectGoogle Scholar
4

General Procedure for the Synthesis of Compounds 5a-k
To a stirred CH2Cl2 solution (2 mL/1 mmol of starting materials) of 4-chloro-3-nitrocoumarin 3 (1.0 equiv) and 1,3-bis(silyl enol ethers) 4 (1.1 equiv) was added TiCl4 (1.1 equiv) at -78 ˚C under an argon atmosphere. The temperature of the reaction mixture was allowed to rise to 20 ˚C in the period of 12 h. To the solution was added HCl (10%, 20 mL), and the mixture was extracted with CH2Cl2 (3 Ž 20 mL). The combined organic layers were dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, heptanes-EtOAc) to give 5a-k.

5

Methyl 4-(3-Nitro-2-oxo-2 H -chromen-4-yl)-3-oxopentanoate (5b) Starting with 3 (0.338 g, 1.5 mmol) and 4b (0.453 g, 1.65 mmol), 5b was isolated by column chromatography (silica gel, heptanes-EtOAc) as a yellow solid (0.324 g, 68%); mp 135-137 ˚C. R f = 0.21 (heptanes-EtOAc, 4:1). ¹H NMR (250 MHz, CDCl3): d = 1.60 (d, ³ J = 7.0 Hz, 3 H, CH3), 3.35 (d, ² J = 16.0 Hz, 1 H, CH2), 3.50 (d, ² J = 16.0 Hz, 1 H, CH2), 3.61 (s, 3 H, OCH3), 4.00 (q, ³ J = 7.0 Hz, 1 H, CH), 7.30-7.42 (m, 2 H, CHAr), 7.51-7.54 (m, 1 H, CHAr), 7.61-7.66 (m, 1 H, CHAr). ¹³C NMR (75 MHz, CDCl3): d = 15.0 (CH3), 47.0 (CH2), 48.2 (CH), 52.7 (OCH3), 115.3 (CAr), 118.3, 126.0, 126.9 (CHAr), 128.0 (CAr), 134.4 (CHAr), 144.3 (CAr), 152.6 (CO), 152.7 (CAr), 166.4, 198.4 (CO). IR (neat): 3117 (w), 3079 (w), 3045 (w), 2992 (w), 2962 (w), 2929 (w), 1732 (s), 1704 (s), 1605 (m), 1536 (s), 1436 (m), 1362 (m), 1323 (m), 1282 (s), 1155 (m), 1070 (m), 1030 (m), 989 (s), 872 (m), 835 (m), 767 (s), 693 (m), 657 (m), 580 (m), 547 (m) cm-¹. ESI-MS: m/z calcd for C15H13NNaO7 [M + Na]+: 342.0584; found: 342.0591. Anal. Calcd for: C15H13NNaO7: 56.43; H, 4.08; N, 4.39. Found: C, 56.94; H, 4.36; N, 4.21.

6

Methyl 4-(3-Nitro-2-oxo-2 H -chromen-4-yl)-3-oxohexanoate (5c)
Starting with 3 (0.338 g, 1.5 mmol) and 4c (0.476 g, 1.65 mmol), 5c was isolated by column chromatography (silica gel, heptanes-EtOAc) as a yellow solid (0.288 g, 58%); mp 99-100 ˚C. R f = 0.32 (heptanes-EtOAc, 4:1). ¹H NMR (250 MHz, CDCl3): δ = 0.86 (t, ³ J = 7.5 Hz, 3 H, CH2CH 3), 1.81-1.97 (m, 1 H, CHCH 2CH3), 2.31-2.45 (m, 1 H, CHCH 2CH3), 3.35 (d, ² J = 16.1 Hz, 1 H, CH2), 3.54 (d, ² J = 16.1 Hz, 1 H, CH2), 3.59 (s, 3 H, OCH3), 3.67-3.78 (m, 1 H, CH), 7.28-7.41 (m, 2 H, CHAr), 7.59-7.66 (m, 2 H, CHAr). ¹³C NMR (75 MHz, CDCl3): δ = 12.1 (CH3), 22.9, 47.4 (CH2), 52.6 (OCH3), 56.0 (CH), 115.5 (CAr), 118.2, 126.0, 127.2 (CHAr), 128.1 (CAr), 134.4 (CHAr), 142.8 (CAr), 152.6 (CO), 152.7 (CAr), 166.4, 198.1 (CO). IR (neat): 2975 (w), 2957 (w), 2923 (w), 2877 (w), 1737 (s), 1719 (s), 1605 (m), 1544 (s), 1436 (m), 1362 (m), 1327 (m), 1245 (s), 1148 (s), 1069 (m), 1047 (m), 994 (m), 899 (m), 837 (m), 774 (m), 755 (s), 656 (s), 590 (m), 561 (m), 533 (m) cm-¹. ESI-MS: m/z calcd for C16H16NO7 [M + H]+: 334.09213; found: 334.09214. Anal. Calcd for C16H15NO7: C, 57.66; H, 4.51; N, 4.20. Found: C, 57.52; H, 4.50; N, 4.16.

7

General Procedure for the Synthesis of Chromeno[3,4- b ]pyrrol-4(3 H )-ones 6a-k In a 50 mL one-neck round Schlenk flask under a flow of dry argon were placed 1.0 mmol of coumpound 5 and 0.05 g of Pd/C (10%). Afterwards, 25 mL of dry degassed MeOH was added. The system was washed three times with H2. The hydrogenation was conducted with the help of a glass burette under atmospheric pressure. After 3 equiv of H2 was consumed, the mixture was stirred for 3 d at 20 ˚C (TLC control). The reaction mixture was filtered through a Celite pad (2-3 cm). The Celite was washed 3 times with MeOH. The solvent of the filtrate was removed under reduced pressure. The residue was purified by preparative chromatography (silica gel, heptanes-EtOAc).

8

Methyl 2-{3,4-Dihydro-1-methyl-4-oxochromeno[3,4- b ]pyrrol-2-yl}acetate (6b)
Starting with 5b (0.100 g, 0.31 mmol), 6b was isolated (0.043 g, 51%) by column chromatography (silica gel, heptanes-EtOAc) as a white solid; mp 211-213 ˚C. R f = 0.21 (heptanes-EtOAc, 1:1). ¹H NMR (250 MHz, CDCl3): δ = 2.36 (s, 3 H, CH3), 3.70 (s, 3 H, OCH3), 3.77 (s, 2 H, CH2), 7.23-7.37 (m, 3 H, CHAr), 7.87-7.90 (m, 1 H, CHAr), 10.26 (s, 1 H, NH). ¹³C NMR (75 MHz, CDCl3): δ = 11.0 (CH3), 31.3 (CH2), 52.6 (OCH3), 113.5, 116.2 (CAr), 117.5 (CHAr), 119.1 (CAr), 123.3, 124.2, 127.3 (CHAr), 127.5 (CAr), 132.1, 151.3 (CAr), 155.5, 169.9 (CO). IR (neat): 3220 (m), 2953 (w), 2919 (m), 2851 (w), 1730 (m), 1692 (s), 1592 (m), 1504 (m), 1428 (m), 1340 (m), 1276 (s), 1199 (s), 1170 (m), 1147 (s), 1110 (m), 1043 (m), 998 (m), 981 (s), 894 (m), 812 (m), 749 (s), 737 (s), 660 (m), 621 (m), 567 (m), 536 (m). GC-MS (EI, 70 eV): m/z (%) = 271 (60)[M]+, 212 (100), 198 (3), 184 (7), 128 (5). cm-¹. HRMS (EI): m/z calcd for C15H14NO4 [M + H]+: 272.0917; found: 272.0923.

9

Methyl 2-{1-Ethyl-3,4-dihydro-4-oxochromeno[3,4- b ]pyrrol-2-yl}acetate (6c)
Starting with 5c (0.100 g, 0.31 mmol), 6c was isolated (0.060 g, 67%) by column chromatography (silica gel, heptanes-EtOAc) as a white solid; mp 199-201 ˚C. R f = 0.22 (heptanes-EtOAc, 1:1). ¹H NMR (250 MHz, CDCl3): δ = 1.19 (t, ³ J = 7.5 Hz, 3 H, CH2CH 3), 2.79 (q, ³ J = 7.6 Hz, 2 H, CH 2CH3), 3.68 (s, 3 H, OCH3), 3.78 (s, 2 H, CH2), 7.21-7.38 (m, 3 H, CHAr), 7.82-7.85 (m, 1 H, CHAr), 10.44 (s, 1 H, NH). ¹³C NMR (75 MHz, CDCl3): δ = 14.8 (CH3), 18.3, 31.3 (CH2), 52.6 (OCH3), 116.3 (CAr), 117.6 (CHAr), 118.8, 120.4 (CAr), 123.3, 124.3 (CHAr), 126.8 (CAr), 127.3 (CHAr), 132.0, 151.2 (CAr), 155.6, 170.0 (CO). IR (neat): 3218 (w), 2966 (w), 2951 (w), 2931 (w), 2875 (w), 1738 (m), 1681 (s), 1674 (s), 1610 (m), 1555 (m), 1456 (m), 1424 (m), 1301 (m), 1253 (m), 1230 (m), 1148 (s), 1114 (m), 1013 (s), 984 (s), 850 (m), 739 (s), 713 (s), 659 (m), 631 (s), 586 (m), 546 (w) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 285 (100) [M]+, 270 (39), 238 (7), 226 (82), 212 (42), 182 (8), 167 (10). HRMS (EI): m/z calcd for C16H16NO4 [M + H]+: 286.1074; found: 286.1076.