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Synlett 2008(12): 1789-1792  
DOI: 10.1055/s-2008-1078549
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Oxidative Conjugate Hydrothiocyanation-Hydrosulfenylation of Baylis-Hillman Alcohols Promoted by a Protic Ionic Liquid

Lal Dhar Singh Yadav*, Rajesh Patel, Vishnu Prabhakar Srivastava
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
Fax: +91(532)2460533; e-Mail: ldsyadav@hotmail.com;
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Publication History

Received 26 March 2008
Publication Date:
02 July 2008 (online)

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Abstract

The first example of one-pot oxidative conjugate hydro­thiocyanation-hydrosulfenylation of acrylic ester derived Baylis-Hillman alcohols, that is, methyl 3-aryl-3-hydroxy-2-methylene­propanoate, is reported. The reaction involves protic ionic liquid [Hmim]HSO4-mediated oxidation of Baylis-Hillman alcohols with NaNO3 to give methyl (E)-α-formylcinnamates followed by conjugate addition of sulfur-centered nucleophiles (NH4SCN/PhSH) to afford the corresponding methyl β-thiocyanato (or β-phenylsulfenyl)-α-formylhydrocinnamates diastereoselectively in 74-87% yields in a one-pot procedure. After isolation of the product, the ionic liquid [Hmim]HSO4 could be easily recycled for further use without any loss of efficiency.

Key words

Baylis-Hillman alcohols - conjugate addition - oxidation - protic ionic liquids - methyl cinnamates - stereoselective synthesis

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General Procedure for the Synthesis of Methyl β-Thiocyanato-α-formylhydrocinnamates 3 and Methyl β-Phenylsulfenyl-α-formylhydrocinnamates 4 A mixture of BH alcohol 1 (1 mmol) and NaNO3 (1 mmol) was stirred in 1 mL of [Hmim]HSO4 at 80 ˚C for 1-3 h (Table  [²] ). The reaction mixture was cooled to r.t. and NH4SCN or PhSH (1.1 mmol) was added. The mixture was further stirred at r.t. for 2-3 h. After completion of the reaction (monitored by TLC), the product was extracted with EtOAc (3  10 mL). The combined extract was dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane-EtOAc, 8.5:1.5) to afford the desired product 3 or 4. After isolation of the product, the remaining ionic liquid was washed with Et2O (2  10 mL) to remove any organic impurity, then H2SO4 (2.1 mmol in the case of compound 3 and 1 mmol in the case of 4) was added, the mixture was stirred at 80 ˚C for 1 h, and cooled to about -5 ˚C in an ice-salt bath. The precipitated solid [Na2SO4, (NH4)2SO4] was filtered out, and the filtrate was dried under vacuum to afford the IL [Hmim]HSO4, which was used in subsequent runs.
Data of Representative Compounds Compound 3a: white solid, yield 78%, mp 104-105 ˚C. IR (KBr): 3026, 2115, 1745, 1718, 1603, 1578, 1460, 1284, 1194, 764, 714 cm-¹. ¹H NMR (400 MHz, CDCl3, TMS): d = 3.68 (dd, 1 H, J = 3.9, 2.1 Hz, 2-H), 3.82 (s, 3 H, MeOCO), 4.86 (d, 1 H, J = 3.9 Hz, 3-H), 7.14-7.32 (m, 5 Harom), 9.56 (d, 1 H, J = 2.1 Hz, CHO). ¹³C NMR (100 MHz, CDCl3, TMS): d = 36.6, 63.9, 52.8, 112.4, 126.9, 128.6, 129.2, 140.9, 169.1, 198.3. MS (EI): m/z = 249 [M+]. Anal. Calcd (%) for C12H11NO3S: C, 57.82; H, 4.45; N, 5.62. Found: C, 57.56; H, 4.57; N, 5.43.
Compound 4f: yellowish solid, yield 76%, mp 132-133 ˚C. IR (KBr): 3055, 2932, 1746, 1721, 1586, 1520, 1345, 1280, 1186, 760, 710 cm-¹. ¹H NMR (400 MHz, CDCl3, TMS): d = 3.72 (dd, 1 H, J = 3.9, 2.1 Hz, 2-H), 3.81 (s, 3 H, MeOCO), 4.68 (d, 1 H, J = 3.9 Hz, 3-H), 7.24-8.27 (m, 9Harom), 9.54 (d, 1 H, J = 2.1 Hz, CHO). ¹³C NMR (100 MHz, CDCl3, TMS): d = 30.6, 52.7, 64.2, 121.6, 124.9, 127.4, 129.2, 129.8, 135.8, 148.2, 149.4, 169.0, 198.3. MS (EI): m/z = 345 [M+]. Anal. Calcd (%) for C17H15NO5S: C, 59.12; H, 4.38; N, 4.06. Found: C, 59.33; H, 4.74; N, 3.89.

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General Procedure for the Synthesis of Methyl ( E )-α-Formylcinnamates 2 A stirred solution of BH alcohols 1 (1 mmol) and NaNO3 (1 mmol) in 1 mL of [Hmim]HSO4 was heated at 80 ˚C for 1-3 h (Table  [²] ). The reaction progress was monitored by TLC. Upon completion, the reaction mixture was cooled to r.t. and extracted with EtOAc (3 × 10 mL).The combined organic phase was dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting crude product was purified by silica gel column chromatography using a gradient mixture of hexane-EtOAc (8:2) as eluent to give the pure cinnamates 2. The remaining ionic liquid was recycled for subsequent runs as described above using H2SO4 (1 mmol).¹6
Data of Representative Compound Compound 2a: white solid, yield 80%, mp 91-92 ˚C. IR (KBr): 3076, 2809, 2740, 1724, 1684, 1578, 1462, 1286, 1190, 760, 712 cm-¹. ¹H NMR (400 MHz, CDCl3, TMS): δ = 3.87 (s, 3 H, MeOCO), 7.48-7.70 (m, 3 Harom), 7.86 (s, 1 H, CHPh), 8.04-8.12 (m, 2 Harom), 9.66 (s, 1 H, CHO). ¹³C NMR (100 MHz, CDCl3, TMS): δ = 52.6, 127.7, 129.4, 130.2, 131.3, 134.7, 154.6, 167.9, 187.6. MS (EI): m/z = 190 [M+]. Anal. Calcd (%) for C11H10O3: C, 69.46; H, 5.30. Found: C, 69.81; H, 5.14.