Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme

Ynamides in Ring Forming Transformations

• ACS ActiveView PDFHi-Res Print, Annotate, Reference QuickView
• PDF [4886 KB]
• PDF w/ Links[2137 KB]
• Full Text HTML

• Abstract
• Figures
• Reference QuickView
• Add to ACS ChemWorx

Xiao-Na Wang †, Hyun-Suk Yeom †, Li-Chao Fang †, Shuzhong He †, Zhi-Xiong Ma †, Brant L. Kedrowski *‡, and Richard P. Hsung *†

^† Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53705, United States

^‡ Department of Chemistry, University of Wisconsin, Oshkosh, Wisconsin 54901, United States

Acc. Chem. Res., Article ASAP

DOI: 10.1021/ar400193g

Publication Date (Web): October 28, 2013

 

Abstract

The ynamide functional group activates carbon–carbontriple bonds through an attached nitrogen atom that bears an electron-withdrawing group. As a result, the alkyne has both electrophilic and nucleophilic properties. Through the selection of the electron-withdrawing group attached to nitrogen, chemists can modulate the electronic properties and reactivity of ynamides, making these groups versatile synthetic building blocks. The reactions of ynamides also lead directly to nitrogen-containing products, which provides access to important structural motifs found in natural products and molecules of medicinal interest. Therefore, researchers have invested increasing time and research in the chemistry of ynamides in recent years.

This Account surveys and assesses new organic transforma-tions involving ynamides developed in our laboratory and in others around the world. We showcase the synthetic power of ynamides for rapid assembly of complex molecular structures. Among the recent reports of ynamide transformations, ring-forming reactions provide a powerful tool for generating molecular complexity quickly. In addition to their synthetic utility, such reactions are mechanistically interesting. Therefore, we focus primarily on the cyclization chemistry of ynamides.

This Account highlights ynamide reactions that are useful in the rapid synthesis of cyclic and polycyclic structural manifolds. We discuss the mechanisms active in the ring formations and describe representative examples that demonstrate the scope of these reactions and provide mechanistic insights. In this discussion, we feature examples of ynamide reactions involving radical cyclizations, ring-closing metathesis, transition metal and non-transition metal mediated cyclizations, cycloaddition reactions, and rearrangements. The transformations presented rapidly introduce structural complexity and include nitrogen within or in close proximity to a newly formed ring (or rings). Thus, ynamides have emerged as powerful synthons for nitrogen-containing heterocycles and nitrogen-substituted rings, and we hope this Account will promote continued interest in the chemistry of ynamides.