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Synlett 2010(17): 2649-2653  
DOI: 10.1055/s-0030-1258586
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

N-Heterocyclic Carbene Catalyzed Cross Coupling of Aromatic Aldehydes with Baylis-Hillman Bromides: An Easy Access to α-Arylidene-γ-keto Esters

Pankaj Singha, Santosh Singha, Vijai K. Raia,b, Lal Dhar S. Yadav*a
a Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Fax: +91(532)2460533; e-Mail: ldsyadav@hotmail.com;
b School of Biotechnology, Shri Mata Vaishno Devi University, Katra, Jammu & Kashmir 182 320, India
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Publication History

Received 25 July 2010
Publication Date:
23 September 2010 (online)

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Abstract

N-Heterocyclic carbene catalyzed carbonyl umpolung reaction of aldehydes with Baylis-Hillman (BH) bromides as activated halides were realized for the first time. This intermolecular cross-coupling reaction features the easily available catalyst and mild reaction conditions to provide α-arylidene- γ-keto esters in excellent yields for a wide range of substrates. Thus, the present work opens up a new aspect of the synthetic utility of BH adducts via the reactivity umpolung of aldehydes.

Key words

N-heterocyclic carbenes - umpolung - acyl anion - ­Baylis-Hillman bromides - α-arylidene- γ-keto esters

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General Procedure for the Synthesis of α-Arylidene-γ-keto Esters 4
A flame-dried round-bottom flask was charged with benzimidazolium salt 3c (0.25 mmol), aldehyde 1 (1.0 mmol), and THF (5 mL) under positive pressure of nitrogen followed by addition of DBU (0.25 mmol) with a syringe. After stirring for 10 min at r.t., BH bromide 2 (1.0 mmol) was added. The reaction mixture was stirred at r.t. for 12-18 h (Table  [²] ). After completion of the reaction (the disappearance of 2, monitored by TLC), the reaction mixture was concentrated under reduce pressure. The residue was purified by flash column chromatography using hexane-EtOAc as eluent to afford product 4 in 65-85% yield.
Characterization Data of Representative Compounds 4
Compound 4a: IR (film) : νmax = 1714, 1642 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3 H, OMe), 5.20 (s, 2 H, CH2), 7.57-7.25 (m, 8 Harom, Ph), 7.88-7.80 (m, 2 Harom, Ph), 8.02 (s, 1 H, C = CH). ¹³C NMR (100 MHz, CDCl3/TMS): δ = 40.6, 52.5, 126.1, 127.2, 128.1, 128.9, 129.7, 130.6, 133.4, 135.6, 137.2, 138.5, 166.5, 193.4. MS (EI): m/z = 280 [M+]. Anal. Calcd for C18H16O3: C, 77.12; H, 5.75. Found: 77.44; H, 5.96.
Compound 4c: IR (film): νmax = 1712, 1640 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 2.30 (s, 3 H, Me), 3.86 (s, 3 H, OMe), 5.14 (s, 2 H, CH2), 7.50-7.19 (m, 5 Harom, Ph), 7.90-7.77 (m, 4 Harom, 4-MePh), 7.96 (s, 1 H, C = CH). ¹³C NMR (100 MHz, CDCl3/TMS): δ = 25.4, 41.5, 53.1, 126.2, 127.1, 127.9, 128.7, 129.4, 130.2, 134.34, 135.41, 138.2, 143.3, 167.3, 193.2.MS (EI): m/z = 294 [M+]. Anal. Calcd for C19H18O3: C, 77.53; H, 6.16. Found: C, 77.86; H, 6.54.
Compound 4d: IR (film): νmax = 1709, 1638 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 3.80 (s, 3 H, OMe), 3.84 (s, 3 H, OMe), 5.20 (s, 2 H, CH2), 7.55-7.22 (m, 5 Harom, Ph),
7.38-7.28 (m, 2 Harom, 4-MeOPh), 7.86-7.82 (m, 2 Harom,
4-MeOPh), 7.98 (s, 1 H, C = CH). ¹³C NMR (100 MHz, CDCl3/TMS): δ = 40.3, 52.8, 55.1, 114.2, 126.5, 127.5, 128.1, 129.1, 129.8, 130.7, 134.9, 137.6, 165.8, 167.3, 191.2. MS (EI): m/z = 310 [M+]. Anal. Calcd for C19H18O4: C, 73.52; H, 5.85. Found: C, 73.18; H, 5.50.
Compound 4k: IR (film): νmax = 1711, 1636 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 3.80 (s, 3 H, OMe), 3.83 (s, 3 H, OMe), 5.15 (s, 2 H, CH2), 7.32-7.22 (m, 4 Harom, 4-ClPh), 7.37-7.30 (m, 2 Harom, 4-MeOPh), 7.85-7.80 (m, 2 Harom,
4-MeOPh), 7.98 (s, 1 H, C = CH). ¹³C NMR (100 MHz, CDCl3/TMS): δ = 47.3, 52.4, 55.1, 113.8, 127.5, 128.3, 129.1, 129.9, 130.6, 133.1, 134.1, 137.9, 165.9, 167.6, 192.2. MS (EI): m/z = 344 [M+]. Anal. Calcd for C19H17ClO4: C, 66.19; H, 4.97. Found: C, 66.50; H, 4.79.