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Synlett 2003(11): 1619-1622
DOI: 10.1055/s-2003-41007
LETTER
© Georg ThiemeVerlag Stuttgart ˙ New York

A Versatile Protocol for theSynthesis of Oxazole and 3-Nitro/3-Carbethoxy Pyrrole C-Nucleosides using TOSMIC [1]

Palakodety Radha Krishna*, Vuyyuru V. Ramana Reddy, Gangavaram V. M. Sharma
D-206/B, Discovery Laboratory,Organic Chemistry Division III, Indian Instituteof Chemical Technology, Hyderabad-500 007, India
Fax: +91(40)27160387; e-Mail: prkgenius@iict.ap.nic.in;
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Publication History

Received 21 May 2003
Publication Date:
11 August 2003 (online)

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Abstract

The synthesis of oxazole and pyrrole C-nucleosides usingTOSMIC in moderate to good yields is reported.

Key words

oxazole - pyrrole - C-nucleosides - TOSMIC - sugar derivatives

1

IICT Communication number 030312.

1

IICT Communication number 030312.

18

General ExperimentalProcedures: Method A: To a stirred solution of aldehyde 1 (0.08 g, 0.39 mmol) in MeOH (2 mL), K2CO3 (0.16g, 1.18 mmol) and TOSMIC (0.077 g, 0.39 mmol) were added and stirredat reflux for 1 h. The reaction mixture was diluted with EtOAc (20mL), washed with H2O (10 mL), brine (10 mL), dried (Na2SO4)and concentrated. The residue was subjected to column chromatography(silica gel, 25% EtOAc:hexane) to afford 1a (0.030g, 33%) as a syrup. [α]D -35.2(c 1.0, CHCl3). 1H NMR(200 MHz, CDCl3): δ = 1.30 (s, 3 H,-CH3), 1.50 (s, 3 H, -CH3), 3.12 (s, 3 H,OMe), 3.80 (d, J 3,4 = 3.7Hz, 1 H, H-3), 4.60 (d, J 2,1 = 7.4Hz, 1 H, H-2), 5.20 (d, J 4,3 = 3.5 Hz, 1 H, H-4),5.96 (d, J 1,2 = 6.7Hz, 1 H, H-1), 7.03 (s, Ar-H, 1 H), 7. 89 (s, Ar-H, 1 H). 13CNMR (50 MHz, CDCl3): δ = 26.09, 26.75,58.05, 74.11, 81.96, 84.89, 104.61, 111.96, 125.93, 146.64, 150.70.IR (KBr): 3380, 2760, 1510, 1380 cm-1. Method B: To a stirred solution of potassium t-butoxide (0.046 g, 0.41mmol) in dryTHF (1 mL) was added TOSMIC (0.053 g, 0.27 mmol) followed by 8 (0.1 g, 0.27 mmol) in dry THF (2 mL)at -78 °C and stirred for 30 min. After the completionof the reaction, sat. NH4Cl (2 mL) was added and thereaction mixture was allowed to come to r.t. and stirred for 15min. The organic compound was extracted into EtOAc (2 × 20mL), washed with H2O (10 mL), brine (10 mL), dried (Na2SO4)and concentrated. The residue was subjected to column chromatography(silica gel, 20% EtOAc:hexane) to afford the product 8a (0.049 g, 44%) as a syrup. [α]D -61.6(c 1.0, CHCl3). 1HNMR (CDCl3, 200 MHz): δ = 0.09 (s,6 H), 0.95 (s, 9 H, 3 × CH3),1.23 (s, 6 H, 2 × CH3),3.65 (br. s, 2 H, CH2OTBS), 4.05 (t, J 4,5 = 3.8Hz, 1 H, H-4), 4.87 (d, J 2,1 = 5.2Hz, 1 H, H-2), 5.01 (dd, J 3,4 = 4.2, J 3,2 = 5.7Hz, 1 H, H-3), 5.55 (d, J 1,2 = 4.0Hz, 1 H, H-1), 6.70 (s, 1 H, Ar-H) 7.53 (s, Ar-H, 1 H). 13CNMR (75 MHz, CDCl3): δ = 18.12, 24.90,25.81, 26.12, 29.65, 64.92, 78.99, 81.74, 83.23, 83.71, 112.07,117.54, 118.36, 120.56, 134.37. MS-FAB: m/z (%) = 399(19) [M+ + 1], 355(24), 281 (12), 221 (14), 147 (32), 73 (100). IR (neat): 3140, 2930, 2870,1570, 1380 cm-1. Anal. Calcd for C18H30N2O6Si:C, 54.25; H, 7.59; N, 7.03. Found: C, 54.22; H, 7.55; N, 7.01. Compound 4a. [α]D -52.4(c 1.0, CHCl3). 1HNMR (300 MHz, CDCl3): δ = 1.36 (s,3 H, CH3), 1.55 (s, 3 H, CH3), 3.20 (s, 3H, -OMe), 4.19 (d, J 3,4 = 3.6Hz, 1 H, H-3), 4.61 (d, J 2,1 = 6.0Hz, 1 H, H-2), 5.61 (d, J 4,3 = 3.6Hz, 1 H, H-4), 5.95 (d, J 1,2 = 6.0Hz, 1 H, H-1), 6.88 (s, Ar-H, 1 H), 7.61 (Ar-H, 1 H). 13CNMR (50 MHz, CDCl3): δ = 26.32, 26.81, 29.62,58.17, 82.83, 84.15,104.23, 111.94, 115.64, 118.90, 120.86, 134.45.IR (KBR): 3480, 2960, 1490, 1340 cm-1. MS-FAB: m/z (%) = 385(25) [M + 1], 281 (2), 221 (2), 147 (6),111 (16), 97 (32), 57 (100). Mp146-148 °C. Anal.Calcd for C12H16N2O6:C, 50.70; H, 5.67; N, 9.85. Found: C, 50.64; H, 5.62; N, 9.78. Method C: To a stirred solution of TOSMIC(0.05 g, 0.26 mmol) in dry THF (2 mL) was added n-BuLi(0.24 mL, 1.6 M solution in hexane) followed by 9 (0.1g, 0.26 mmol) dissolved in dry THF (2 mL) at -78 °C andstirred for 30 min. After the completion of the reaction, the reactionmixture was quenched with aq sat. NH4Cl solution (2 mL)and allowed to attain r.t. in 15 min. The organic compound was extractedinto EtOAc (2 × 20 mL), washed with H2O(10 mL), brine (10 mL), dried (Na2SO4) andconcentrated. The residue was subjected to column chromatography(silica gel, 20% EtOAc:hexane) to afford 9a (0.058g, 53%) as a syrup. [α]D -34.0(c 1.0, CHCl3). 1H NMR(200 MHz, CDCl3): δ = 0.09 (s, 6 H),0.95 (s, 9 H, 3 × CH3), 1.20-1.40(9 H), 3.74 (d, J 5,4 = 4.6Hz, 2 H, -CH2OTBS), 4.10 (t, J 4,5 = 4.8Hz, 1 H, H-4), 4.19-4.3 (m, 2 H, -OCH2CH3),4.82 (d, J 2,1 = 4.8 Hz, 1 H, H-2),5.01 (dd, J 3,4 = 4.6, J 3,2 = 5.8Hz, 1 H, H-3), 5.55 (d, J 1,2 = 3.9Hz, 1 H, H-1), 6.82 (s, Ar-H, 1 H), 7.30 (s, Ar-H, 1 H), 8.30 (br.s, 1 H, NH). 13C NMR (75 MHz, CDCl3): δ = 14.47,18.28, 25.14, 25.91, 26.33, 59.43, 63.35, 78.88, 81.91, 83.84, 83.71,111.96, 118.43, 124.06, 128.33. MS-FAB: m/z (%) = 426 (52) [M+ + 1],380 (23), 366 (46), 281 (48), 222 (54), 218(100). Anal. Calcd forC21H35NO6Si: C, 59.26; H, 8.29; N,3.29. Found: C, 59.21; H, 8.22; N, 3.25. Compound 5a. [α]D -69.3(c 1.0, CHCl3). 1HNMR (300 MHz, CDCl3): δ = 1.30-1.60(m, 6 H) 1.55 (s, 3 H), 3.21 (s, 3 H, OMe), 4.10 (d, J 3,4 = 6.0Hz, 1 H, H-3), 4.22-4.30 (m, 2 H, -OCH2CH3), 4.60(d, J 2,1 = 6.0 Hz, 1 H, H-2),5.65 (d, J 4,3 = 5.6Hz, 1 H, H-4), 5.94 (d, J 1,2 = 6.0Hz, 1 H, H-1), 6.82 (s, Ar-H, 1 H), 7. 33 (s, Ar-H, 1 H). 13CNMR (75 MHz, CDCl3): δ = 14.40, 26.33,26.85, 58.26, 59.60, 84.10, 84.53, 104.10, 111.47, 113.12, 118.64,119.47, 124.53, 164.90. IR (KBr): 3350, 2980, 1710, 1340, 1070 cm-1.MS-FAB: m/z (%) = 312 [M + 1],281 (2), 221 (2), 147 (6), 111 (16), 97 (32), 57 (100). Mp 90-93 °C.Anal. Calcd for C15H21NO6: C, 57.87;H, 6.80; N, 9.85. Found: C, 57.81; H, 6.77; N, 9.83.