Rhodium-katalysierte asymmetrische 1,4-Addition von Arylnukleophilen an α,β-ungesättigte N-Tosylketimine

Die konjugierte Addition und damit auch die Rhodium-katalysierte 1,4-Addition von Metallnukleophilen an Michael-Akzeptoren, welche 1997 entdeckt wurde, ist eine der wichtigsten Reaktionen zur Kohlenstoff-Kohlenstoff-Bindungsknüpfung. In Naturstoffen und biologisch aktiven Verbindungen findet man häu...

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Bibliographic Details
Main Author: Gebhardt, Sandra
Contributors: Zezschwitz, Paultheo von (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2016
Online Access:PDF Full Text
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The conjugate addition of carbon nucleophiles is one of the most important reactions for carbon-carbon bond formation. Discovered in 1997, the rhodium-catalyzed 1,4-addition of aryl nucleophiles is a very prominent example of such a reaction and can be performed with various α,β-unsaturated electrophiles. Based on the results from my own master thesis, a method was developed for using various substituted α,β unsaturated N-tosyl imines in the rhodium-catalyzed 1,4-addition of arylzinc halides. The enamides, obtained after aqueous work-up, are sensitive towards chromatography and have therefore been converted into stable amides by reduction. By proper selection of the reduction conditions (Noyori transfer hydrogenation or addition of borane) both, the trans- and the cis-configured N-3-arylcycloalkylsulfonamides, can selectively be obtained. This method was also applied on five-, six- and seven-membered N-busyl imines opening an access to 3-arylcycloalkylamines as well as 3-aminocycloalkylcarbonic acids, which are subunits in a number of bioactive substances. Despite the sensibility of the enamides towards hydrolysis, the method was extended to the transformation of the imines with phenylboronic acid in an aqueous medium. It was also shown that in the case of the N-tosyl imines derived from 5-substituted cyclohex-2-enone the rhodium/binap catalyst outweighs substrate control; this can be used for the selective synthesis of all four diastereomers of 3-alkyl-5-arylcyclohexylamides. The synthesis of 3-aminocyclohexanecarboxylic acids was achieved by 1,4-addition, reduction, Boc protection, detosylation, and oxidative degradation of the aryl group in a Lemieux-von Rudloff-oxidation without loss of diastereoselectivity. First results on the reactivity of the intermediate zinc-aza-enolate were achieved: Bromination of the zinc-aza-enolates with N-bromosuccinimide and subsequent Strecker reaction furnished α-quaternary N-sulfonamides. In addition, the in situ transformation of the zinc-aza-enolate with different alkylating reagents was successful; a subsequent microwave-assisted Aza-Claisen rearrangement, however, proceeded in low regioselectivity.