Decreasing Distortion Energies without Strain: Diazo-Selective 1,3-Dipolar Cycloadditions.

Content Provider	Semantic Scholar
Author	Gold, Brian H. Aronoff, Matthew R. Raines, Ronald T.
Copyright Year	2016
Abstract	The diazo group has attributes that complement those of the azido group for applications in chemical biology. Here, we use computational analyses to provide insights into the chemoselectivity of the diazo group in 1,3-dipolar cycloadditions. Dipole distortion energies are responsible for ∼80% of the overall energetic barrier for these reactions. Here, we show that diazo compounds, unlike azides, provide an opportunity to decrease that barrier substantially without introducing strain into the dipolarophile. The ensuing rate enhancement is due to the greater nucleophilic character of a diazo group compared to that of an azido group, which can accommodate decreased distortion energies without predistortion. The tuning of distortion energies with substituents in a diazo compound or dipolarophile can enhance reactivity and selectivity in a predictable manner. Notably, these advantages of diazo groups are amplified in water. Our findings provide a theoretical framework that can guide the design and application of both diazo compounds and azides in "orthogonal" contexts, especially for biological investigations.
Starting Page	5998
Ending Page	6006
Page Count	9
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://biochem.wisc.edu/sites/default/files/labs/raines/pdfs/gold2016a.pdf
Alternate Webpage(s)	http://raineslab.com/sites/default/files/labs/raines/pdfs/Gold2016a.SuppInfo.pdf
PubMed reference number	27332711v1
Alternate Webpage(s)	https://doi.org/10.1021/acs.joc.6b00948
DOI	10.1021/acs.joc.6b00948
Journal	The Journal of organic chemistry
Volume Number	81
Issue Number	14
Language	English
Access Restriction	Open
Subject Keyword	Azides Complement System Proteins Energy, Physics
Content Type	Text
Resource Type	Article