| Author: | Cheung, Hong-yee |
| Title: | Development of new chiral chelating ferrocenyl ligands for transition metal catalyzed asymmetric carbon-carbon bond formations : a modular approach for ligand design and synthesis |
| Degree: | Ph.D. |
| Year: | 2008 |
| Subject: | Hong Kong Polytechnic University -- Dissertations. Organometallic chemistry. Organic compounds -- Synthesis. |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | xxii, 408 p. : ill. ; 30 cm. |
| Language: | English |
| Abstract: | Several classes of chiral C1-symmetrical P/S-, N/S-, P/N- and P/P-type ligands with ferrocene and N-heterocycles as scaffold were prepared via a two-to-three-step modular synthesis from (S)-Ugi's amine. A variety of N-heterocycles such as imidazole, benzimidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, benzotriazole and indazole was coupled with the substituted (S)-Ugi's amines in excellent yields without racemization. The molecular structures of PS1, PS4, PS9, NS1-NS6, PP5 and Pd(PS8)Cl2 complex have been determined by X-ray crystallography with absolute configuration being (S,Rp). The heterobidentate P/S-type ligands have been applied for the Pd-catalyzed enantioselective allylic alkylation. Using [Pd(allyl)Cl]2 (2.5 mol%) as catalyst and 1-{(S)-1-[(R)-2-(ethylthio)ferrocenyl]ethyl}-2-(diphenylphosphino)- benzimidazole (PS8) as ligand, 1,3-dipenyl-2-propenyl acetate reacted with dimethyl malonate to give the alkylated products in up to 96% ee. Bulkier substituted malonates are effective substrates in the reaction with 94-96% ee being attained. The first Pd-catalyzed enantioselective allylic alkylation of indoles with 1,3-dipenyl-2-propenyl acetate using PS8 was also achieved in 56-85% yield and 94-96% ee. Other established chiral phosphine ligands such as BINAP, PHOX and the Trost ligands afforded poor results in terms of reactivity and stereoselectivity. The Pd-catalyzed allylic alkylation of unsymmetrical allylic carbonates such as methyl 1-phenyl-2-propenyl carbonate would generally favor substitution at the less hindered terminus leading to achiral linear alkylated products. We found that excellent branch-to-linear selectivity can be attained using Rh(acac)(C2H4)2 (3 mol%) and 1-{(S)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyl}-2-(diphenylphosphino)-imidazole (PP1) as ligand (3 mol%). The enantioselective allylic alkylation of methyl 1-phenyl-2-propenyl carbonate with dimethyl malonate furnished the alkylated product with >99/1 branch-selectivity and up to 92% ee. Ligands PP2-PP5 were less effective in terms of selectivity and enantioselectivity. The catalyst system was also found to be highly dependent on the electronic properties of the substituent of the allylic carbonates. Moreover, we developed highly diastereoselective and enantioselective Ag(I)-catalyzed 1,3-dipolar cycloaddition reaction of azomethine ylides using our ferrocenyl ligands. Ligand screening studies revealed that 1-{(S)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyl}-2-(diphenylphosphino)be-nzim idazole (PP5) was the most effective ligand for Ag(I)-catalyzed 1,3-dipolar cycloaddition. The Ag-PP5 system was highly efficient with turnover frequency (TOF) up to 100 N being attained. Under the optimized reaction conditions: AgOAc (0.5 mol%), PP5 (0.5 mol%) and Hunigs base (10 mol%) in THF, the reaction of N-benzylideneglycine methyl ester and V-methylmaleimide afforded for the corresponding cycloadduct with nearly complete endo-selectivity (up to >99/1), quantitative yield and 91% ee in 2 h. The catalytic system was tolerated with a wide variety of N-arylideneglycine methyl ester. The absolute configuration of the endo-cycloadduct was determined to be (lS,3R,3aS,6aR) by X-ray crystallography. |
| Rights: | All rights reserved |
| Access: | open access |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| b22761858.pdf | For All Users | 10.96 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/200/3723