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

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 nucleophilicit...

Full description

Saved in:
Bibliographic Details
Published inJournal of organic chemistry Vol. 88; no. 11; pp. 6868 - 6877
Main Authors Gazizov, Almir S., Smolobochkin, Andrey V., Rizbayeva, Tanzilya S., Vatsadze, Sergey Z., Burilov, Alexander R., Sinyashin, Oleg G., Alabugin, Igor V.
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 02.06.2023
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Lewis bases
moieties
nitrogen
organic chemistry
Physical Sciences
Science & Technology
urea
viability
CATALYSIS
ACYCLIC AMIDES
DONOR
CONSEQUENCES
HYDROLYSIS
PLANAR
BOND
DERIVATIVES
UREA
ACCEPTOR
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.3c00161