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 Fatunsin; Viktor O. Iaroshenko; Sergii Dudkin; Mohanad Shkoor; Dmitro Volochnyuk; Ashot Gevorgyan; Peter Langer

doi:10.1055/s-0029-1220068

LETTER

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 Fatunsin^a, Viktor O. Iaroshenko*^a,b, Sergii Dudkin^a, Mohanad Shkoor^a, Dmitro Volochnyuk^b,c, Ashot Gevorgyan^a, 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

Abstract

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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

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References

References and Notes

<A NAME="RG05710ST-1A">1a</A> Kennedy RO. Thorenes RD. Coumarins: Biology, Applications, Mode of Action Wiley; Chichester: 1997.

For reviews, see:

<A NAME="RG05710ST-1B">1b</A> Yu DL. Suzuki M. Xie L. Morris-Natschke SL. Lee KH. Med. Res. Rev. 2003, 23: 322

<A NAME="RG05710ST-1C">1c</A> Fylaktakidou KC. Hadjipavlou-Litina DJ. Litines KE. Nicolaides DN. Curr. Pharm. Res. 2004, 10: 3813

<A NAME="RG05710ST-1D">1d</A> Borges F. Roleira F. Mihazes N. Santana L. Uriarte E. Curr. Med. Chem. 2005, 12: 887

<A NAME="RG05710ST-2">2</A> Chen L. Xu MH. Adv. Synth. Catal. 2009, 351: 2005 ; and references 2-5 cited therein

<A NAME="RG05710ST-3">3</A> For a review, see: Langer P. Synthesis 2002, 441

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.

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, CH_Ar), 7.51-7.54 (m, 1 H, CH_Ar), 7.61-7.66 (m, 1 H, CH_Ar). ^¹³C NMR (75 MHz, CDCl₃): d = 15.0 (CH₃), 47.0 (CH₂), 48.2 (CH), 52.7 (OCH₃), 115.3 (C_Ar), 118.3, 126.0, 126.9 (CH_Ar), 128.0 (C_Ar), 134.4 (CH_Ar), 144.3 (C_Ar), 152.6 (CO), 152.7 (C_Ar), 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.

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, CH_Ar), 7.59-7.66 (m, 2 H, CH_Ar). ^¹³C NMR (75 MHz, CDCl₃): δ = 12.1 (CH₃), 22.9, 47.4 (CH₂), 52.6 (OCH₃), 56.0 (CH), 115.5 (C_Ar), 118.2, 126.0, 127.2 (CH_Ar), 128.1 (C_Ar), 134.4 (CH_Ar), 142.8 (C_Ar), 152.6 (CO), 152.7 (C_Ar), 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.

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).

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, CH_Ar), 7.87-7.90 (m, 1 H, CH_Ar), 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 (C_Ar), 117.5 (CH_Ar), 119.1 (C_Ar), 123.3, 124.2, 127.3 (CH_Ar), 127.5 (C_Ar), 132.1, 151.3 (C_Ar), 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.

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, CH_Ar), 7.82-7.85 (m, 1 H, CH_Ar), 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 (C_Ar), 117.6 (CH_Ar), 118.8, 120.4 (C_Ar), 123.3, 124.3 (CH_Ar), 126.8 (C_Ar), 127.3 (CH_Ar), 132.0, 151.2 (C_Ar), 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.