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Diastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric (Z)-Benzamidines.

ABSTRACT: 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.

SUBMITTER: Jaffett VA

PROVIDER: S-EPMC8448149 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Diastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric (Z)-Benzamidines.

Jaffett Victor A VA Fitz-Henley Jhewelle N JN Khalifa Muhammad M MM Guzei Ilia A IA Golden Jennifer E JE

Organic letters 20210712 15

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 ...[more]

PMID: 34251832

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