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Synlett 2009(16): 2613-2616  
DOI: 10.1055/s-0029-1217761
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel DABCO-Catalyzed Regio- and Diastereoselective Nucleophilic Substitution of Baylis-Hillman Acetates with TosMIC

Palakodety Radha Krishna*, Y. Lakshmi Prapurna
D-211, Discovery Laboratory, Organic Chemistry Division-III, Indian Institute of Chemical Technology, Hyderabad 500607, India
e-Mail: prkgenius@iict.res.in;
Further Information

Publication History

Received 18 June 2009
Publication Date:
04 September 2009 (online)

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Abstract

An efficient DABCO-mediated regio- and diastereoselective substitution of Baylis-Hillman acetates with p-toluenesulfonylmethyl isocyanide (TosMIC) has been developed via a tandem SN2′-SN2′ mechanism. The products were obtained in excellent yields (80-92%) and in moderate diastereoselectivity (66-80%).

Key words

Baylis-Hillman acetates - p-Toluenesulfonylmethyl isocyanide (TosMIC) - DABCO

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On the advice of one of the referees and in order to ascertain whether the postulated mechanism is directing the product formation or a direct substitution reaction is the path followed, an independent reaction was conducted under similar reaction conditions wherein TosMIC was treated with DABCO first for 1 h at r.t., and then acetate 1 was added. The reaction was found to be sluggish even after 24 h. Hence it may be inferred that a disubstitution could be the plausible mechanistic pathway.

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General Experimental Procedure
To a solution of Baylis-Hillman acetate (1.0 mmol) and DABCO (0.3 mmol) in CH2Cl2 (3.0 mL) TosMIC (1.0 mmol) was added and stirred for 1-2 h at r.t. After completion of the reaction as indicated by TLC, H2O (5 mL) was added, and the product was extracted with CH2Cl2 (2 × 10 mL). The combined organic layers were washed with brine, dried (Na2SO4), and purified by column chromatog-raphy (silica gel, 60-120 mesh, EtOAc-n-hexane = 1:9 to 2:8) to afford products 2a-h in 80-92% yields.

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Spectral Data for Selected Compounds
Compound 2a: ¹H NMR (400 MHz, CDCl3): δ = 7.81 (d, 2 H, J = 8.30 Hz, ArH), 7.41-7.16 (m, 7 H, ArH), 6.38 (s, 1 H, olefinic), 5.87 (s, 1 H, olefinic), 5.75 (d, 0.90 H, J = 8.68 Hz, CHAr), 5.48 (d, 0.10 H, J = 11.70 Hz, CHAr), 4.44 (d, 1 H, J = 8.49 Hz, CHTos), 4.30-4.06 (m, 2 H, CH2), 2.48 (s, 3 H, CH3), 1.39 (t, 3 H, J = 7.17 Hz, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 14.0, 21.8, 48.5, 61.2, 73.2, 128.0, 128.6, 128.8, 129.8, 131.9, 135.7, 137.5, 146.2, 165.4, 166.4. IR (KBr): 2982, 2134, 1708, 1322, 1148, 757, 705, 664, 566 cm-¹.
LC-MS: m/z = 383.9 [M + H]+. Anal. Calcd (%) for C21H21NO4S: C, 65.78; H, 5.52; N, 3.65. Found: C, 65.81; H, 5.50; N, 3.68.
Compound 2b: ¹H NMR (400 MHz, CDCl3): δ = 7.81-7.72 (m, 2 H, ArH), 7.62-7.33 (m, 6 H, ArH), 6.41 (s, 1 H, olefinic), 5.82 (s, 1 H, olefinic), 5.61 (d, 0.88 H, J = 8.03 Hz, CHAr), 5.42 (d, 0.12 H, J = 9.67 Hz, CHAr), 4.62 (d, 1 H, J = 8.05 Hz, CHTos), 4.30-4.01 (m, 2 H, CH2), 2.49 (s, 3 H, CH3), 1.34-1.18 (m, 3 H, CH3). ¹³C NMR (75 MHz, CDCl3): δ = 13.9, 21.8, 47.8, 61.6, 72.6, 112.3, 118.2, 129.3, 129.5, 129.8, 130.0, 130.1, 132.4, 136.9, 140.9, 146.8, 165.1, 167.5. IR (KBr): 2985, 2229, 1707, 1317, 1146, 756, 576 cm-¹. LC-MS: m/z = 407 [M - H]+. Anal. Calcd (%) for C22H20N2O4S: C, 64.69; H, 4.94; N, 6.86. Found: C, 64.67; H, 4.97; N, 6.89.
Compound 2d: ¹H NMR (300 MHz, CDCl3): δ = 7.76 (d, 2 H, J = 8.30 Hz, ArH), 7.33 (d, 2 H, J = 8.30 Hz, ArH), 7.19 (d, 1 H, J = 3.77 Hz, ArH), 7.09 (d, 1 H, J = 3.07 Hz, ArH), 6.91 (q, 1 H, J = 3.77 Hz, ArH), 6.44 (s, 1 H, olefinic), 5.92 (s, 1 H, olefinic), 5.57 (d, 0.87 H, J = 7.55 Hz, CHAr), 5.37 (d, 0.13 H, J = 9.63 Hz, CHAr), 4.94 (d, 1 H, J = 7.55 Hz, CHTos), 4.30-4.05 (m, 2 H, CH2), 2.47 (s, 3 H, CH3), 1.36 (t, 3 H, J = 6.79 Hz, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 14.2, 21.8, 44.2, 61.2, 74.8, 125.9, 126.7, 128.6, 129.4, 129.7, 130.0, 132.0, 138.0, 146.2, 165.0, 165.6. IR (KBr): 2982, 2134, 1708, 1322, 1148, 757, 705, 664, 566 cm-¹. LC-MS: m/z = 389 [M + H]+. Anal. Calcd (%) for C19H19NO4S2: C, 58.59; H, 4.92; N, 3.60. Found: C, 58.61; H, 4.94; N, 3.63.
Compound 2h: ¹H NMR (400 MHz, CDCl3): δ = 7.81 (d, 2 H, J = 8.02 Hz, ArH), 7.35 (d, 2 H, J = 8.00 Hz, ArH), 6.37 (s, 1 H, olefinic), 5.78 (s, 1 H, olefinic), 4.82 (d, 0.88 H, J = 6.83 Hz, CHTos), 4.79 (d, 0.12 H, J = 7.88 Hz, CHTos), 4.29-4.12 (m, 2 H, CH2), 3.71-3.68 (m, 1 H, CHCH3), 2.50 (s, 3 H, CH3), 1.43 (d, 3 H, J = 6.59 Hz, CH3), 1.34 (t, 3 H, J = 7.31 Hz, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 13.6, 14.1, 21.9, 34.8, 61.3, 74.8, 128.6, 129.4, 130.0, 138.5, 146.2, 165.1, 165.6. IR (KBr): 2974, 2133, 1705, 1505, 1317, 1146, 1084, 1022, 812, 759, 670, 577, 521 cm-¹. LC-MS: 321 [M - H]+. Anal. Calcd (%) for C16H19NO4S: C, 59.79; H, 5.96; N, 4.36. Found: C, 59.81; H, 5.94; N, 4.33.