Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

DESIGN AND SYNTHESIS OF CHIRAL N-HETEROCYCLIC CARBENES WITH APPLICATIONS TO ASYMMETRIC SYNTHESES AND SYNTHESIS OF DIBENZAZEPINONES BY PALLADIUM¨CCATALYZED INTRAMOLECULAR ARYLATION OF O-(2¡¯-BROMOPHENYL)ANILIDE ENOLATES

pan, xiaohong (2011) DESIGN AND SYNTHESIS OF CHIRAL N-HETEROCYCLIC CARBENES WITH APPLICATIONS TO ASYMMETRIC SYNTHESES AND SYNTHESIS OF DIBENZAZEPINONES BY PALLADIUM¨CCATALYZED INTRAMOLECULAR ARYLATION OF O-(2¡¯-BROMOPHENYL)ANILIDE ENOLATES. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

[img]
Preview
 PDF
Primary Text
Download (3MB) | Preview

Abstract

Chiral N-heterocyclic carbene (NHC) ligands were prepared and examined in three asymmetric syntheses (oxindole synthesis, pyrrolidine synthesis and cyanosilylation of aldehydes). The ligand generated from (4R,5R)-1,3-bis(ortho-cyclohexylphenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-3-ium tetrafluoroborate provided the best asymmetric oxindole synthesis: yields of oxindoles up to 99% with enantioselectivities (ee) up to 80% were achieved in 3 h; catalyst loadings as low as 1 mol % could be used; the imidazolinium salt can be made efficiently in only two steps. A mechanism for this asymmetric oxindole synthesis was proposed. The rotation barrier of the N-aryl bond in the oxidative addition products was found crucial for the enantioselectivity.A new approach for the convenient synthesis of dibenzazepinones is reported. The key step is the formation of the seven-membered ring through palladium-catalyzed intramolecular arylation of an anilide enolate. The reactions were completed in 10 min at 100 ¡ãC with moderate to excellent yields. Aminodibenzazepinone, the core structure in secretase inhibitor LY411575, can be prepared in five steps from 2-bromophenylboronic acid and 2-iodoaniline in 60% overall yield. The synthesis reported here compares favorably with presently available approaches to this interesting ring system.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
pan, xiaohongxip4@pitt.eduXIP4
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWilcox, Craigdaylite@pitt.eduDAYLITE
Committee MemberDoemling, Alexanderasd30@pitt.eduASD30
Committee MemberCurran, Denniscurran@pitt.eduCURRAN
Committee MemberNelson, Scottsgnelson@pitt.eduSGNELSON
Date: 29 September 2011
Date Type: Completion
Defense Date: 18 May 2011
Approval Date: 29 September 2011
Submission Date: 28 May 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: dibenzazepinone; N-heterocyclic carbene; oxindole
Other ID: http://etd.library.pitt.edu/ETD/available/etd-05282011-005856/, etd-05282011-005856
Date Deposited: 10 Nov 2011 19:46
Last Modified: 15 Nov 2016 13:44
URI: http://d-scholarship.pitt.edu/id/eprint/7972

Metrics

Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item