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Synlett 2010(15): 2322-2344  
DOI: 10.1055/s-0030-1258023
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Copper-Free Sonogashira Cross-Coupling of Ynamides: Easy Access to ­Various Substituted Ynamides from Nonsubstituted Ynamides

Hideaki Wakamatsu*, Mitsuhiro Takeshita
Department of Organic Reaction Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
e-Mail: hiwaka@tohoku-pharm.ac.jp;
Further Information

Publication History

Received 21 May 2010
Publication Date:
09 August 2010 (online)

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Abstract

It is demonstrated herein that palladium-catalyzed Sonogashira cross-coupling of ynamides can be accomplished with moderate to good yields of substituted ynamides in the absence of copper salt, and NaOAc plays an important role in this reaction as an additive.

Key words

carboxylate anion - copper-free - cross-coupling - palladium - ynamide

9

Typical Procedure for Sonogashira Cross-Coupling Reaction of Ynamide 1 Promoted by Palladium Acetate
To a solution of ynamide 1 (53.7 mg, 0.19 mmol), Pd(OAc)2 (2.1 mg, 9.41 mmol, 5 mol%), Ph3P (4.9 mg, 18.82 mmol, 10 mol%), and NaOAc (23.2 mg, 0.28 mmol, 1.5 equiv) in DMF (6 mL) was added methyl 4-iodobenzoate 2 (0.04 mL, 0.23 mmol, 1.2 equiv) at 0 ˚C under argon atmosphere. The reaction mixture was stirred at 80 ˚C for 1 h. After the consumption of starting ynamide 1 was confirmed by TLC analysis, the resulting mixture was cooled to 0 ˚C. H2O (12 mL) was added to the mixture, which was extracted with Et2O (3 × 50 mL). The organic phase was washed with brine and dried under MgSO4. The volatiles were removed under reduce pressure. The residue was separated by column chromatography on silica gel (hexane-EtOAc, 10:1) to afford 3 (61.0 mg, 75%).