Synthesis of various acylating agents directly from carboxylic acids

Abstract

A straightforward synthesis of acylating reagents such as Weinreb and MAP amides from aromatic, aliphatic carboxylic acids, and amino acids using PPh₃/NBS combination is described. A chemo-selective modification of the carboxylic acid group into Weinreb amide in the presence of more reactive aldehydes and ketones is presented. All reactions were performed at ambient temperature under air using undried commercial grade solvent. Furthermore, the present methodology could be performed at a gram scale under inert-free reaction conditions. In addition, 7-azaindoline amide auxiliary (used for catalytic asymmetric aldol- and Mannich-type reactions), which behaves like Weinreb amide is also synthesized under similar reaction conditions.

Graphical Abstract

Keywords:

• MAP amide
• Meyers and Comins amide
• N-methoxy-N-methylamide
• N-methylaminopyridine amide
• Weinreb amide

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors thank IISER Thiruvananthapuram for financial support. One of the authors (F.P) thank UGC, New-Delhi for senior research fellowship.