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Title: Development of cobalt(III) and rhodium(III)-catalyzed electrophilic aminations of organoboronic acids with Ο-protected hydroxamic acids and azo compounds and ruthenium(II)-catalyzed three-component cascade coupling reactions of α, β-unsaturated enones with organoboronic acids and Ν-chlorophthalimide
Authors: Lau, Yan Fung
Degree: Ph.D.
Issue Date: 2018
Abstract: Arylation of simple amines to construct highly biological-valued compounds remains a major challenge in synthetic chemistry. N-arylhydrazines and aliphatic / aromatic N-arylamines / amides are common motifs in bioactive natural compounds, pharmaceuticals, synthetic intermediates and advanced functional materials. Extensive effort has been directed to developing generally applicable methods for C-N bond formation. Notable achievements include copper-catalyzed Ullmann-Goldberg coupling reaction and palladium-catalyzed Buchwald-Hartwig amination. Complementary to the classical nucleophile amination reactions, catalytic amination employing "R₂N+" as an electrophilic nitrogen source is attracting increasing attention for chemo and regioselective amination. Developments of earth-abundant first-row transition metals and catalysts for catalytic cross coupling reaction in mild reaction conditions are attracting considerable interest. Our group has succeeded in developing the Pd(II)- and Rh(III)-catalyzed electrophilic amination reactions. Based on our previously developed Rh-catalyzed electrophilic arene C-H aminations, we explored [Cp*Co(III)]-catalyzed electrophilic amination of organoboronic acids with O-carbonyl hydroxylamines / amides, which are easily prepared and widely employed for stoichiometric electrophilic amination reactions. We began the reaction by treating O-acetylbenzohydroxamic acid (0.2 mmol), p-methoxyphenylboronic acid (0.3 mmol), [Cp*CoI₂(CO)] (5 mol%), AgSbF₆(40 mol%) and KOAc (40 mol%) in DCE (1 mL) at 40 °C under an N₂ atmosphere for 4 hours afforded benzanilide in 78% yield. Under the Co-catalyzed conditions, arylboronic acids containing electron-donating and -withdrawing groups (e.g. OMe and halides) afforded the corresponding anilides in 51-78% yields. Other functionalized arylboronic acids bearing TMS, CHO, C(O)Me, CO₂Me and vinyl were effectively aminated in excellent yields. Analogous amidation of 2-naphthyl, 6-methoxy-1-naphthyl and styrylboronic acids were accomplished in 54-82% yields. With phenylboronic acid as the arylating reagent, the scope of O-carbonyl hydroxylamines / amides was examined. O-Acetylarylhydroxamic acids bearing electron-donating and -withdrawing groups (e.g. Me, OMe, Cl and Br) afforded the corresponding anilides in 55-92% yields. Other O-acetyl hydroxamic acids containing tert-butyl, 2-naphthyl and aliphatic carbamates were obtained in 7-72% yields. Facile transformations of some primary amine hydroxamic acid such as O-benzoyl (ethoxycarbonyl)methylhydroxamic acid was also achieved in 99% yield. However, no product was obtained from O-benzoyl morpholinehydroxamic acid.
Characterized by the N-N π-bond, unlike the halo / hydroxyamine-type reagents, difunctionalization of the azo compounds with carbanionic nucleophiles with high atom economy can be achieved. Our investigation began with the [Cp*Rh(III)]-catalyzed cross coupling reactions of arylboronic acids with azo compounds for arylhydrazides and N,N-diarylhydrazides synthesis. In this work, treatment of phenylboronic acid (0.3 mmol), diethyl azodicarboxylate (DEAD) (0.2 mmol) and [Cp*Rh(OAc)₂] (2 mol%) in DMF (1 mL) at 40 °C under an N₂ atmosphere for 4 hours afforded phenylhydrazide in 99% yield. Under the Rh-catalyzed conditions, a wide scope of arylhydrazides and N,N-diarylhydrazides were obtained in 73-99% yields (28 examples) with excellent chemo- and regioselectivity. Remarkable functional group tolerance was also demonstrated. The molecular structure of 2-(4-methoxyphenyl)-2-phenyl-,1-ethylhydrazinecarboxylic acid ester has been established by single-crystal X-ray crystallography. To examine the involvement of the arylrhodium(III) complexes, [Cp*Rh(Ph)Br(PPh₃)] complex was prepared. When [Cp*Rh(Ph)Br(PPh₃)] (10 mol%) was treated with AgSbF6 (10 mol%) and phenylazocarboxylate (0.5 mmol) in DMF at 40 °C under an N₂ atmosphere for 4 hours, formation of any N,N-diphenylazocarboxylate was not detected. Thus, the involvement of the arylrhodium(III) intermediate for the C-N bond coupling reaction is untenable. Furthermore, when methanol-d4 was employed as the solvent for he Rh-catalyzed reaction, the N-phenyl diethylhydrazinedicarboxylate product obtained 18% yield. Notably, no deuterated-hydrazide product was obtained. Our findings implicated that the organoboronic acids probably play dual role as both the aryl and proton sources for the reaction. Based on our initial success of the Co / Rh-catalyzed coupling of arylboroniuc acids with electrophilic "R₂N+" reagents, we began our exploration on catalytic three-component coupling reactions. Our investigation by treating p-bromophenylboronic acid (0.4 mmol), but-1-en-3-one (0.3 mmol), N-chlorophthalimide (0.2 mmol), [(p-cymene)RuCl₂]₂ (2.5 mol%) and Na₂CO₃ (30 mol%) in CHCl₃(2 mL) at ambient temperature for 19 hours, and the desired 3-chloro-4-(4-bromophenyl)butan-2-one was obtained in 93% yield. Under the Ru-catalyzed conditions, arylboronic acids containing electron-donating and -withdrawing groups (e.g. OMe and halides) afforded the corresponding ketones in 76-93% yields. Other functionalized arylboronic acids bearing TMS, CHO, C(O)Me, SO₂Me and vinyl were effectively coupled in excellent yields. With p-bromophenylboronic acid as the arylating reagent, the scope of the α,β-unsaturated enones was examined. Facile transformations of aliphatic and aromatic enones were achieved in 88-99% yields. However, no product was obtained from 5-membered to 7-membered conjugated cyclic enones. Application of the Ru-catalyzed arylchlorination of enones for synthesis of quinoxialines was performed.
Subjects: Hong Kong Polytechnic University -- Dissertations
Organic compounds -- Synthesis
Organoboron compounds
Organic acids
Pages: xlv, 396 pages : illustrations
Appears in Collections:Thesis

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