Preparation of N-Acetyl-2-arylglycin Esters by N-H Insertion Reaction of Aryldiazoacetates with Acetamide

Abstract

The intermolecular N-H insertion reaction of methyl α-diazo α-arylacetate with acetamide has been investigated using transition-metal complexes as catalysts. The Cu(II) complex Cu(hfacac)₂ (hfacac represents hexafluoroacetylacetonate) has proven to be the most active catalyst to yield methyl N-acetyl-2-phenylglycin in good isolated yield (73–80%) with 3 mmol% of catalyst loading in reflux toluene. The catalyst is also valuable to the substituted aryldiazoacetates at the 4-position on phenyl ring.

Keywords:

• Acetamide
• α-diazo arylacetate ester
• N-acetyl-2-arylglycin ester
• N-H insertion
• synthesis

ACKNOWLEDGMENTS

Financial support from the Natural Science Foundation of Jiangsu (Project KB2005043) and Jiangnan University (Project Q21050712) is gratefully acknowledged. We thank Prof. Q. Shen and Prof. M. Yan for their useful suggestions.

Notes

^a The reactions were carried out with 1.5 mmol diazo, 1.0 mmol acetamide, and 0.01 mmol Rh₂(OAc)₄ under reflux.

^b Isolated yield after column chromatography.

^a The reactions were carried out with 1.5 mmol diazo, 1.0 mmol aceamino in reflux with toluene.

^b Isolated yields after column chromatography.

^c Cu(acac)₂ = acetylacetonate copper(II).

^d Cu(hfacac)₂ = copper(II)-bis-(hexafluoroacetylacetonate).

^e Cu(OTf)₂ = copper(II)-bis-(trifluoromethanesulfonate).

^a The reactions were carried out with 1.5 mmol diazo and 1.0 mmol acetamide in refluxing toluene by catalysis of 3 mmol% Cu(hfacac)₂.

^b Isolated yield after column chromatography.