Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
| dc.creator | Tsoi, Yuk Tai | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/6579 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | - |
| dc.rights | All rights reserved | en_US |
| dc.title | Exploration of α-diazocarbonyl compounds for transition-metal catalyzed carbon-carbon bond formations : development of palladium-catalyzed stereoselective synthesis of trisubstituted alkenes and the synthesis of quaternary α, α-heterodiaryl carboxylic acids by rhodium -catalyzed multi-component coupling reactions | en_US |
| dcterms.abstract | Transition-metal catalyzed decomposition of α-diazo carbonyl compounds are proved to be a versatile approach for carbenoid-mediated carbon-carbon bond formations. It is widely accepted that highly reactive metal-carbenoid complexes are involved to undergo cyclopropanation, C-H insertion and ylide reactions. However, due to the isoelectronic property of carbene with carbon monoxide, migratory insertion of carbene to metal-carbon bond is less established. In this research, we explored the transition-metal carbenoid for cross-coupling reactions involving migratory carbene insertion reactions as a key step. Our approach involves the formation of organometallic complexes, which can be further transformed to metal-carbene complexes. The subsequent migratory carbene insertion would afford a new organometallic complex with a new C-C bond being formed. The reactivity of the new organometallic complexes can be further exploited for C=C bond and C-C bond formations. Our investigation began by studying the stereoselective synthesis of α,β-diarylacrylates, which are common scaffolds in pharmaceutically active compounds. Perkin aldol condensation is conventionally employed for α,β-diarylacrylates synthesis; however, it suffers from limited substrate scope and low product yields. In this work, we developed a stereoselective cross-coupling reaction of benzyl bromides with α-aryldiazoesters to give (E)-α,β-diarylacrylates. Employing Pd₂(dba)₃·CHCl₃ (10 mol% Pd, dba: dibenzylideneacetone) and PPh₃ (40 mol%) as catalyst, the diarylacrylates were obtained in up to 92% yield and >20: 1 E-to-Z selectivity. Pertinent to the mechanism, we examined the stoichiometric reaction of a benzylpalladium(II) complex [BnPd(PPh₃)₂Br, 7a] with methyl phenyldiazoacetate, and (E)-methyl 2,3-diphenylacrylate was formed in 75% yield. Based on this finding, it is plausible that the cross-coupling reaction proceeded by migratory carbene insertion to the benzylpalladium complex, followed by β-hydride elimination to give the acrylate product. | en_US |
| dcterms.abstract | In view of the medicinal value of (E)-α,β-diarylacrylates, our earlier catalytic reaction is limited by the use of reactive halides and required excess PPh₃ for operation. Thus, it is unlikely to be environmentally-sound for sustainable synthesis. In this work, we developed an oxidative cross-coupling reaction for the synthesis of (E)-α,β-diarylacrylates with O₂ as the sole oxidant. Employing Pd(OAc)₂ (5 mol%) and 1,10-phenanthroline (5.5 mol%) as catalyst, diazoesters would react with arylboronic acids (1.2 equiv) to afford (E)-α,β-diarylacrylates in up to 80% yield and >20: 1 E-to-Z selectivity. Other functionalized (E)-α,β-diarylacrylates containing chloro, bromo, trimethylsilyl, nitro, sulfonyl and acetyl have been successfully prepared. In this work, we prepared a phenylpalladium(II) complex [PhPd(1,10-phenanthroline)OAc, 10a], which has been structurally characterized by X-ray crystallography. Reacting [PhPd(1,10-phenanthroline)OAc] with methyl 2-diazo-3-phenylpropanoate produced (E)-methyl 2,3-diphenylacrylate in 72% yield. Therefore, migratory carbene insertion is probably a key step for the cross-coupling reaction. Apart from the C=C bond formation, we also succeeded in constructing a quaternary stereocenter at the carbenic carbon by forming two C-C σ bonds. In this work, we developed a one-pot rhodium-catalyzed three-component coupling reaction for the synthesis of quaternary α,α-heterodiaryl carboxylic esters. Employing [Rh(cod)OH₂ (2 mol% Rh, cod: 1,5-cyclooctadiene) as catalyst and KOtBu as base, α-aryldiazoesters would cross couple with arylboronic acids and alkyl halides to furnish quaternary α,α-heterodiaryl carboxylic esters in up to 88% yield. Various functional groups such as chloro, bromo, trifluoromethyl, trimethylsilyl, diphenylamino and sulfonyl were well tolerated in the coupling reaction. Quaternary α,α-diaryl carbonyl compounds are common scaffolds in pharmaceutical compounds such as methadone (dolophine HCl). α,α-Diaryl carbonyl compounds are commonly prepared by Friedel-Crafts reactions, which suffer from limited substrate scope and poor regioselectivity. The rhodium-catalyzed coupling reaction probably proceeded by the migratory carbene insertion of a rhodium-carbenoid species, followed by transmetallation with KOtBu and enolate alkylations. | en_US |
| dcterms.extent | xxviii, 307 leaves : ill. ; 30 cm. | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2012 | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.educationalLevel | Ph.D. | en_US |
| dcterms.LCSH | Transition metal compounds. | en_US |
| dcterms.LCSH | Organic compounds -- Synthesis. | en_US |
| dcterms.LCSH | Organometallic compounds. | en_US |
| dcterms.LCSH | Hong Kong Polytechnic University -- Dissertations | en_US |
| dcterms.accessRights | open access | en_US |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| b25226745.pdf | For All Users | 13.37 MB | Adobe PDF | View/Open |
Copyright Undertaking
As a bona fide Library user, I declare that:
- I will abide by the rules and legal ordinances governing copyright regarding the use of the Database.
- I will use the Database for the purpose of my research or private study only and not for circulation or further reproduction or any other purpose.
- I agree to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage.
By downloading any item(s) listed above, you acknowledge that you have read and understood the copyright undertaking as stated above, and agree to be bound by all of its terms.
Please use this identifier to cite or link to this item:
https://theses.lib.polyu.edu.hk/handle/200/6579