A Domino Ring-Closure Followed by Retro-Diels-Alder Reaction for the Preparation of Pyrimido[2,1-a]isoindole Enantiomers

TitleA Domino Ring-Closure Followed by Retro-Diels-Alder Reaction for the Preparation of Pyrimido[2,1-a]isoindole Enantiomers
Publication TypeJournal Article
Year of Publication2016
AuthorsFekete, B, Palko, M, Mándity, I, Haukka, M, Fulop, F
JournalEuropean Journal of Organic Chemistry
Volume2016
Pagination3519–3527
ISSN1434-193X
Abstract

A simple method was developed to prepare pyrimido[2,1-a]isoindole derivatives by using di-endo- and di-exo-ethyl 3-aminobicyclo[2.2.1]hept-5-ene-2-carboxylate enantiomers as chiral sources. The method is based on a domino ring-closure reaction of norbornene 2-aminohydroxamic acid followed by microwave-induced retro-Diels-Alder reaction. In the case of enantiomeric starting substances, the chirality is transferred from norbornene derivatives to pyrimido[2,1-a]isoindoles. The configurations of the synthesized compounds were determined by 1D and 2D NMR spectroscopy [based on 2D NOE cross-peaks and (3)J(H,H) coupling constants] and X-ray crystallography.