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. 2019 Jul 19;24(14):2628.
doi: 10.3390/molecules24142628.

Intramolecular Carbene C-H Insertion Reactions of 2-Diazo-2-sulfamoylacetamides

Chuqiang Que  1 , Peipei Huang  1 , Zhanhui Yang  1 , Ning Chen  1 , Jiaxi Xu  2
Affiliations

Intramolecular Carbene C-H Insertion Reactions of 2-Diazo-2-sulfamoylacetamides

Chuqiang Que et al. Molecules. .

Abstract

The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo-N,N-dimethyl-2-(N,N-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its N-phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[c]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(N,N-dialkylsulfamoyl)acetamides; and (3) for 2-diazo-N-phenyl-2-(N-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the N-phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the N-aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group.

Keywords: C-H insertion; amide; carbene insertion; competitive reaction; diazo compound; sulfonamide; sultam.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Scheme 1
Scheme 1
Intramolecular carbene C-H insertion reactions of diazoacetamide derivatives and acyl diazomethanesulfonamides.
Scheme 2
Scheme 2
Synthesis of 2-diazo-2-sulfamoylacetamides.
Scheme 3
Scheme 3
Proposed mechanism for the intramolecular aromatic 1,5-C-H insertion of diazosulfamoylacetamides 1.
See this image and copyright information in PMC

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