Synthesis of atropisomeric 2,2'-disubstituted-3,3'-quinazolin-4,4'-diones and their application in asymmetric synthesis

• Main Author: Pertusati, Fabrizio
• Published: Cardiff University 2007
• Subjects: 547.59
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.584109

This thesis reports all the efforts made in the synthesis of 2,2'-disubstituted-3,3'-quinazolin-4,4'-ones (BiQ), a new class of atropisomeric molecules derived from the 4-quinazolinone scaffold, and their potential application as chiral auxiliaries in asymmetric synthesis. Chapter 1 provides first an overview of axial chirality and atropisomerism and then it reports a review of asymmetric reactions such as Diels-Alder, 1,3-dipolar cycloaddition, epoxydation and cyclopropanation, which have been used in literature as a model for the development of new chiral auxiliaries and chiral ligands. Chapter 2 describes first the synthesis of a series of 2-substituted benzoxazinones and 3-amino-2-substitute-quinazolinones units. Then the successful synthesis of racemic symmetrical and unsymmetrical 2,2'-disubstituted-3,3'-quinazolin-4,4'-ones (BiQ) by condensation of benzoxazinones and aminoquinazolinones units is presented. Chapter 3 presents the design and synthesis of chiral non racemic unsymmetrical and symmetrical biquinazolinones. Once chirality has been introduced via the functionalization of 3-aminoquinazolinone with non-racemic amino acids, the corresponding unsymmetrical biquinazolines were produced using the same methodology previously adopted for the racemic unsymmetrical biquinazolinones. Chapter 4 highlights the unexpected synthesis of 4-isopropyl-3-oxo-l,9a,10- triazaanthracen-9-ones. Full characterization of this new heterocyclic compound is herein reported together with the development of an efficient methodology (good to high yield, no chromatographic purification) for the synthesis of other members of this novel class of compounds. Chapter 5 first presents all the attempts performed for the functionalization of symmetrical 2, 2'-methyl- and 2,2'-ethyl-biquinazolinones via carbanionic chemistry. Lithiation of 2,2'-dimethyl-3,3'-biquinazolinone, and further reaction with aromatic aldehydes led to the corresponding styryl derivates. These compounds were used as a prochiral starting materials in diastereoselective reactions like epoxydation, Diels-Alder, 1,3-dipolar cycloaddition and cyclopropanations in order to assess the efficiency of the biquinazolinones as chiral auxiliaries.