| Author: | Lam, Hon Wah |
| Title: | Development of rhodium(III)-catalyzed arylation and cycloaddition of benzohydroxamic acids and semicarbazones for regioselective C-N and C-C bond formation |
| Advisors: | Yu, Michael Wing-yiu (ABCT) Lau, Chak Po (ABCT) |
| Degree: | Ph.D. |
| Year: | 2016 |
| Subject: | Rhodium catalysts. Organic compounds -- Synthesis. Chemistry, Organic. Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | xxx, 313 pages : color illustrations |
| Language: | English |
| Abstract: | Transition metal-catalyzed electrophilic amination with carbon-nucleophiles is a promising approach for carbon-nitrogen bond formation. In this research, we explored the rhodium(III)-catalyzed cross-coupling reactions of organoboronic acids and hydroxylamines derivatives. Furthermore, catalytic cycloaddition reactions of benzohydroxamic acids / semicarbazones with diazo compounds / alkynes were also accomplished. The arylation of N-alkylhydroxylamines with arylboronic acids was first examined by treating O-benzoyl-N-isopropylhydroxylamine with 6-methoxy-2-naphthaleneboronic acid and [Cp*Rh(OAc)₂] (Cp* = pentamethylcyclopentadiene, OAc = acetate) (0.25 mol%) in MeOH at room temperature for 2 h, and the desired amine 7a was obtained in 90% yield. Likewise, N,N-dialkylhydroxylamines and benzohydroxamic acids are effective substrates for the C-N coupling reactions with the corresponding tertiary amines and amides being formed in 47 - 97% yields. Aliphatic cyclic and acyclic hydroxylamines containing benzyl and heterocyclic moieties were tolerated. [Cp*Rh(Ph)Cl(PPh₃)] was prepared to examine the mechanism of the C-N coupling reaction. Upon reacting phenylrhodium(III) complex with O-benzoyl-N-cyclohexylhydroxylamine and 2a, N-cyclohexylaniline (< 20%) and 7j (80%) were obtained. This finding supports the involvement of the [Ar-Rh] complex as active species. Inspired by our previous finding on the rhodium(III)-catalyzed arene C-H coupling reactions with diazomalonates, we envisioned that a transformation involving formal [4 + 1] cycloaddition of diazo compounds with O-acetyl benzohydroxamic acids should give oxisoindoles as products via reductive elimination of the σ-allylrhodacycle. Treating O-acetyl benzohydroxamic acid 3a with diazomalonate and [Cp*Rh(OAc)₂] (5 mol%) in THF, oxisoindole 9a was produced in 89% yield. Substituents such as -OMe, -Me, -NO₂ and -CF₃ were tolerated and the corresponding oxisoindoles were formed in 76 - 93% yields. Diazo compounds having esters, phenylsulfone, cyano and phosphonate groups are good coupling partners, and their reactions with benzohydroxamic acids gave the corresponding oxisoindoles in up to 90% yields. Notably, alkyl diazoacetates with β-hydrogen atom were good partners for the cycloaddition reaction. The possible β-hydride elimination did not seem to compete effectively with the reductive elimination. To ascertain that the reaction should go through chelation-assisted C-H/N-H deprotonation of O-acetyl benzohydroxamic acid, we reacted 3a (0.12 mmol) with [Cp*Rh(OAc)₂] (0.1 mmol) in THF at 60 °C for 2 h under a N₂ atmosphere. A dinuclear arylrhodium(III)-amide complex was obtained and characterized by X-ray crystallography. This dinuclear arylrhodium(III) complex was catalytically inactive for the cycloaddition reaction. The observed inertness is attributed to the stability of the aza-rhodacyclic complex, which should be difficult to dissociate for diazo coordination. Isoindoles are important scaffolds in materials science. We anticipated that isoindoles could be prepared by the formal [4 + 1] cycloaddition of O-carboxylates oximes with diazo compounds. However, this reaction was unsuccessful in our initial trials due to relative instability of the N-O bond in the reaction conditions. We envisioned that the analogous N-N bond should be more stable, and yet it should serve as an isoelectronic replacement for the N-O bond. In this work, semicarbazones containing a tert-butyl carbazate moiety was examined for the rhodium(III)-catalyzed cycloaddition reaction with alkynes. The tert-butyl carbazate group should serve a leaving group to effect reductive elimination of the rhodacyclic intermediate. By treating semicarbazone 5a with 1-phenyl-1-propyne (6a), [Cp*RhCl₂]₂ (5 mol%), CsOAc (25 mol%) and HOAc (1.2 equiv) in MeOH at 120 °C for 16 h, the desired product isoquinolone 10a was obtained in 93% yield. However, the Rh(III)-catalyzed cycloaddition reaction between semicabazone 5a and diazomalonate (4a) is still under investigation. |
| Rights: | All rights reserved |
| Access: | open access |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| b29012259.pdf | For All Users | 9.2 MB | Adobe PDF | View/Open |
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