Syntheses of heterocycle precursors using cobalt(III) and palladium(II) complexes.

  • C. T. Premakumari Nair

Student thesis: Doctoral ThesisPhD


As indicated by the title of this thesis, the aim of the work described herein was to develop metal-assisted organic syntheses of certain natural products or their intermediates. After a short preface surveying the types of reaction brought about by transition metals, the first three chapters, comprising Part I of this thesis, are devoted to reactions of cobalt(III) complexes, particularly those containing the chelated imine systems [CoL4(NH=CRCO2)]2+ where L = NH3 or ½ NH2 CH2 CH2 NH2 and R = alkyl or aryl. It was hoped that a stereospecific synthesis of proline and isoquinoline derivatives might be achieved using the following three known reactions of these chelated imines, (a) simple nucleophilic addition to >C=N, (b) deprotonation of the imine nitrogen followed by its subsequent alkylation, and (c) deprotonation of the alpha-carbon atom of the C-alkyl group to achieve cyclisatlon to nitrogen.;Attempts to synthesise proline were unsuccessful as the imine nitrogen either could not be alkylated by the appropriate halide, or the reaction yielded inseparable mixtures. Two routes were used in an attempt to synthesise isoquinoline derivatives. The first involved condensation of a coordinated alpha-ketoacid with ammonia in the complex [Co(NH3)5OCOCOR]2+ to produce an imine which could then be alkylated; and the second involved dehydration of a coordinated beta-hydroxy-alpha-amino acid in the ethylenediamine complex [Co(en)2NH2CH(CHOHR)CO2]2+. Neither acid could be obtained readily and as before the final alkylation step could not be achieved. Consequently, this project was terminated at this stage and an investigation into the potential of palladium(II) complexes for similar syntheses was initiated. Hence, the remaining three chapters of Part II of this thesis are concerned with the reactions of orthopalladated tertiary amine complexes (ArCH2NR2-PdC1)2 and their analogues with various substituted alkenes.;The enones, methyl vinyl ketone and ethyl acrylate, and the alkene, acrylonitrile, reacted with di-mu-chlorobis(3,4-dimethoxy-N,N-dimethylbenzylamine-6-C,N)dipalladium(II) by inserting into the Pd-C bond and yielding trans-beta-substituted products of the type ArCH=CHZ where Ar = 3,4-dimethoxybenzylamine and Z = COMe, CO2Et and CN. A range of eight styrene derivatives reacted similarly forming trans-O-aminomethylstilbenes in relatively high yields, unless the styrene contained an o-substituent which led to reduced yields, and in the case of o-chlorostyrene, produced small amounts of the cis-isomer as well as traces of the alpha-alkene, alpha-(o-chlorophenyl)-2-(N,N-dimethylaminoraethyl)-4,5-dimethoxystyrene. These reactions were investigated primarily with a view to converting these trans-o-aminomethylstilbenes to 3-arylisoquinoline derivatives which could be used in the preparation of isoquinoline alkaloids possessing the benzo[c]phenanthridine and berberine skeletons. 3,4-Dimethoxybenzylamines were used because such a substitution pattern is frequent in a number of naturally occurring alkaloids.;The next step in the synthetic route was to functionalise the tertiary amine side-chain of the complexes to facilitate ring closure of the resultant stilbenes. Hence attempts were made to prepare ortnopalladated complexes of the tertiary amines, 3,4-(OMe)2C6H3CH2 NMeR where R = Bz and CO2 Et, and 3,4-(OMe)2C6H3CH(NMeCH2)2, as well as of the imine, phenylhydrazone and oxime derivatives of 3.4-dimethoxybenzaldehyde. Orthopalladation was achieved with the tertiary amine, N-bonzyl-N-methyl-3,4-diraethoxybenzylamine, and the imine, 3,4-dimethoxy-N-methylbenzaldimine, whereas the phenylhydrazone and oxime derivatives yielded only adducts, trans-(ArCH=NR)2PdCl2, where R = NPh or OH. However, the orthopalladated complexes either failed to react with styrene or produced intractable mixtures of products. In an attempt to obtain some information on the Pd-C bond, which might help explain the differences in reactivity of the various complexes, the spectroscopic properties (infrared, 1H and 13C NMR) of representative binuclear cyclometallated complexes and their bridge split products ArCH2NR2-PdCl(MPh3), where M = P or As, were examined, and the first full 13C NMR assignments for such complexes made.
Date of Award1980
Original languageEnglish
Awarding Institution
  • University of Bath

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