Biomaterial Database

Synthesis of 1,5-Substituted Pyrrolidin-2-ones from Donor-Acceptor Cyclopropanes and Anilines/Benzylamines. 2022

Maksim A Boichenko, and Andrey Yu Plodukhin, and Vitaly V Shorokhov, and Danyla S Lebedev, and Anastasya V Filippova, and Sergey S Zhokhov, and Elena A Tarasenko, and Victor B Rybakov, and Igor V Trushkov, and Olga A Ivanova

Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia.

We developed a straightforward synthetic route to pharmacologically important 1,5-substituted pyrrolidin-2-ones from donor-acceptor cyclopropanes bearing an ester group as one of the acceptor substituents. This method includes a Lewis acid-catalyzed opening of the donor-acceptor cyclopropane with primary amines (anilines, benzylamines, etc.) to γ-amino esters, followed by in situ lactamization and dealkoxycarbonylation. The reaction has a broad scope of applicability; a variety of substituted anilines, benzylamines, and other primary amines as well as a wide range of donor-acceptor cyclopropanes bearing (hetero)aromatic or alkenyl donor groups and various acceptor substituents can be involved in this transformation. In this process, donor-acceptor cyclopropanes react as 1,4-C,C-dielectrophiles, and amines react as 1,1-dinucleophiles. The resulting di- and trisubstituted pyrrolidin-2-ones can be also used in subsequent chemistry to obtain various nitrogen-containing polycyclic compounds of interest to medicinal chemistry and pharmacology, such as benz[g]indolizidine derivatives.

UI	MeSH Term	Description	Entries
D003521	Cyclopropanes	Three-carbon cycloparaffin cyclopropane (the structural formula (CH2)3) and its derivatives.
D000588	Amines	A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)	Amine
D000814	Aniline Compounds	Compounds that include the aminobenzene structure.	Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D001596	Benzylamines	Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.	Phenylmethylamine,alpha-Aminotoluene,alpha Aminotoluene
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D058116	Lewis Acids	Any chemical species which accepts an electron-pair from a LEWIS BASE in a chemical bonding reaction.	Lewis Acid,Acid, Lewis,Acids, Lewis