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Synlett 2011(20): 2963-2966  
DOI: 10.1055/s-0031-1289886
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Aqueous-Phase Heck Coupling of 5-Iodouridine and Alkenes under Phosphine-Free Conditions

Joon Hyung Cho, Kevin H. Shaughnessy*
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487-0336, USA
Fax: +1(205)3489104; e-Mail: kshaughn@bama.ua.edu;
Further Information

Publication History

Received 10 August 2011
Publication Date:
11 November 2011 (online)

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Abstract

Palladium-catalyzed Heck couplings between 5-iodouridine and alkenes were carried out in aqueous media in the presence of triethylamine under phosphine-free conditions to give the desired products in high yields. In the absence of phosphine ligand, triethyl­amine appears to play a critical role in both generating the active catalyst species and serving as the base in the reaction.

Key words

aqueous phase - cross-coupling - Heck reaction - nucleosides - palladium

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17

General Procedure for Heck Coupling of 5-IdU: All reagents were purchased from commercial sources and used as received. 5-IdU (0.3 mmol), Pd(OAc)2 (3.4 mg, 0.015 mmol), and TPPTS (17.1 mg, 0.03 mmol, if used) were placed in a round-bottomed flask under nitrogen. Deoxy-genated H2O-MeCN (1:1, 3 mL) was added to the reaction vessel, followed by the addition of the alkene (1.2 mmol) and Et3N (61.0 mg, 0.600 mmol). The reaction was heated in an oil bath at 80 ˚C until RP-HPLC (C-18 column, eluted with a gradient ranging from 10% MeOH in H2O to 100% MeOH in H2O) or RP-TLC [C-18, H2O-MeOH (1:2) eluent] showed complete conversion. The reaction mixture was diluted to 10 mL with H2O-MeOH (1:1) and the pH was adjusted to 6-7 using 10% aq HCl. After removal of solvent, the crude product was purified by chromatography [RP-SiO2, H2O → MeOH-H2O (60:40)].
Butyl ( E )-3-(2′-Deoxyurid-5-yl)propenoate (3): With no phosphine. Yield: 75.0 mg (64%). ¹H NMR (500 MHz, DMSO-d 6): δ = 11.69 (s, 1 H), 8.45 (s, 1 H), 7.39 (d, J = 15.5 Hz, 1 H), 6.88 (d, J = 15.5 Hz, 1 H), 6.17 (dd, J = 6.5, 6.5 Hz, 1 H), 5.29 (d, J = 4.5 Hz, 1 H), 5.20 (t, J = 5.0 Hz, 1 H), 4.28-4.31 (m, 1 H), 4.14 (t, J = 6.8 Hz, 2 H), 3.84 (dd, J = 7.0, 3.5 Hz, 1 H), 3.60-3.72 (m, 2 H), 2.17-2.26 (m, 2 H), 1.60-1.66 (m, 2 H), 1.35-1.43 (m, 2 H), 0.94 (t, J = 7.5 Hz, 3 H). ¹³C NMR (126 MHz, DMSO-d 6): δ = 166.7, 161.6, 149.1, 143.8, 137.8, 116.4, 108.1, 87.5, 84.7, 69.6, 63.4, 60.7, 39.9, 30.2, 18.6, 13.5.