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Synlett 2007(15): 2436-2438  
DOI: 10.1055/s-2007-986638
LETTER
© Georg Thieme Verlag Stuttgart · New York

Copper(II) Triflate as a Double Catalyst for the One-Pot Click Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Benzylic Acetates

Shin-ichi Fukuzawa*, Eiji Shimizu, Satoshi Kikuchi
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
Fax: +81(3)38171895; e-Mail: fukuzawa@chem.chuo-u.ac.jp;
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Publication History

Received 19 June 2007
Publication Date:
28 August 2007 (online)

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Abstract

Copper(II) triflate doubly catalyzed the substitution of benzylic acetates by TMSN3 and the subsequent 1,3-dipolar addition with an alkyne in one pot. This procedure afforded the preparation of 1,4-disubstituted 1,2,3-triazoles in good yields starting from the easily accessible acetates without isolating an organic azide ­using a single catalyst.

Key words

triazole - copper(II) triflate - click reaction

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The Cu(OTf)2-catalyzed reaction of (R)-1-phenylethyl acetate (95% ee) with TMSN3 under the conditions gave the racemate 1-phenylethyl azide. This result suggests that the substitution reaction proceeds with SN1-type reaction.

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The reaction must be carried out in two steps. Mixing of three components, i.e., compound 1, phenylacetylene, and TMSN3, in the presence of the Cu catalyst and additive (DIPEA) in CH2Cl2 (1 mL) did not afford 2, along with recovering the starting compounds. A typical experimental procedure is as follows: In a 20 mL Schlenk tube containing a magnetic stirring bar were charged Cu(OTf)2 (18 mg, 0.05 mmol) and dry CH2Cl2 (1 mL) under a slight pressure of nitrogen. A mixture of 1-phenylethyl acetate (1, 82 mg, 0.5 mmol) and TMSN3 (86 mg, 1.5 mmol) was then added using a syringe through the septum with stirring at r.t. The reaction was monitored by TLC and after the starting acetate had almost disappeared (12 h), phenylacetylene 2 (62 mg, 0.6 mmol) was then added to the mixture followed by DIPEA (95 µL, 0.55 mmol). The mixture was stirred at r.t. for an additional 1 h. The reaction was quenched with H2O, and extracted with EtOAc (3 × 15 mL). The combined extracts were washed with brine, dried over MgSO4, filtered, and the solvent was removed using a rotary evaporator that left a yellow residue. The GC-MS analysis revealed the presence of 2 of which the yield was determined by GC using biphenyl as the internal standard. The product 2 was isolated by preparative TLC (hexane-EtOAc, 4:1); yield, 89 mg, 71%. 1H NMR (300 MHz, CDCl3): δ = 2.00 (d, 3 H, J = 7.1 Hz), 5.86 (q, 1 H, J = 7.1 Hz), 7.30-7.50 (m, 8 H), 7.63 (s, 1 H), 7.80 (d, 2 H, J = 7.3 Hz). 13C NMR (CDCl3): δ = 21.2, 60.1, 118.4, 125.6, 126.4, 128.0, 128.5, 128.7, 128.9, 130.6, 139.8, 147.6. IR (KBr): ν = 3092, 1483, 1459, 1421, 1373, 1349, 1304, 1218, 1175, 1155, 1074, 1038, 1025, 993, 973, 913 cm-1. Anal. Calcd for C16H15N3: C, 77.08; H, 6.06; N, 16.85. Found: C, 76.86; H, 6.14; N, 17.01.