Open AccessDiastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric (Z)-Benzamidines
Author(s) -
Victor A. Jaffett,
Jhewelle Fitz-Henley,
Muhammad M. Khalifa,
Ilia A. Guzei,
Jennifer E. Golden
Publication year - 2021
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.1c01955
Subject(s) - chemistry , diastereomer , quinazolinone , intramolecular force , tautomer , enantiopure drug , stereochemistry , domino , yield (engineering) , cope rearrangement , tandem , derivative (finance) , ring (chemistry) , organic chemistry , enantioselective synthesis , catalysis , materials science , economics , financial economics , metallurgy , composite material
An expedient route to enantiopure, diastereomeric pyrrolopyrazinoquinazolinones was developed following the discovery of a domino quinazolinone rearrangement-intramolecular cyclization of N-H benzamidines. A Ugi-Mumm-Staudinger sequence employing an optically pure proline derivative gave quinazolinones that, upon N -Boc deprotection, rearranged to tautomeric Z -benzamidines. Subsequent spontaneous cyclization afforded 15 diastereomeric pyrazinoquinazolinone pairs in up to 83% overall yield and 89:11 d.r which were separated easily via routine chromatographic purification-the only one required in the entire process.