“Stereoelectronic Deprotection of Nitrogen”: Recovering Nucleophilicity with a Conformational Change

“Stereoelectronic Deprotection of Nitrogen”: Recovering Nucleophilicity with a Conformational Change Full article

Journal

Journal of Organic Chemistry
ISSN: 1520-6904 , E-ISSN: 0022-3263

Output data

Year: 2023, Volume: 88, Number: 11, Pages: 6868-6877 Pages count : 10 DOI: 10.1021/acs.joc.3c00161

Authors

Gazizov Almir S. ¹ , Smolobochkin Andrey V. ¹ , Rizbayeva Tanzilya S. ¹ , Vatsadze Sergey Z. ² , Burilov Alexander R. ¹ , Sinyashin Oleg G. ¹ , Alabugin Igor V. ^1,3

Affiliations

1	Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Science, Arbuzova Str., 8, Kazan 420088, Russian Federation
2	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., Moscow 119991, Russian Federation
3	Department of Chemistry and Biochemistry, Florida State University, Tallahassee Fl 32306, United States

Ureas are often thought of as “double amides” due to the obvious structural similarity of these functional groups. The main structural feature of an amide is its planarity, which is responsible for the conjugation between the nitrogen atom and carbonyl moiety and the decrease of amide nucleophilicity. Consequently, since amides are poor nucleophiles, ureas are often thought of as poor nucleophiles as well. Herein, we demonstrate that ureas can be distinctly different from amides. These differences can be amplified by rotation around one of the ureas’ C–N bonds, which switches off the amide resonance and recovers the nucleophilicity of one of the nitrogen atoms. This conformational change can be further facilitated by the judicious introduction of steric bulk to disfavor the planar conformation. This change in reactivity is an example of “stereoelectronic deprotection,” a concept when the desired reactivity of a functional group is produced by a conformational change rather than a chemical modification. This concept may be used complementarily to the traditional protecting groups. We also demonstrate both the viability and the utility of this concept by the synthesis of unusual 2-oxoimidazolium salts possessing quaternary nitrogen atoms at the urea moiety.

Gazizov A.S. , Smolobochkin A.V. , Rizbayeva T.S. , Vatsadze S.Z. , Burilov A.R. , Sinyashin O.G. , Alabugin I.V.
“Stereoelectronic Deprotection of Nitrogen”: Recovering Nucleophilicity with a Conformational Change
Journal of Organic Chemistry. 2023. V.88. N11. P.6868-6877. DOI: 10.1021/acs.joc.3c00161 WOS Scopus OpenAlex

Web of science:	WOS:001004490800001
Scopus:	2-s2.0-85162253642
OpenAlex:	W4377233679

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OpenAlex	9
Scopus	9
Web of science	9