Asymmetrische 1,4-Additionen von Metallorganylen an einfach und zweifach ungesättigte Ketone und Imine

Die asymmetrische 1,4-Addition von Metallorganylen an Michael-Akzeptoren ist eine der wichtigsten Reaktionen zur enantioselektiven Knüpfung von C,C-Bindungen. Im ersten Teil der vorliegenden Dissertation wurde die Substratbreite der Rhodium/BINAP-katalysierten 1,4-Addition von Alkenylzirconocenen an...

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Bibliographic Details
Main Author: Pfaff, Christopher Bernd
Contributors: Zezschwitz, Paultheo von (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2018
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Table of Contents: The asymmetric conjugate addition (ACA) of organometallic reagents to Michael acceptors is one of the most important reactions for enantioselective formation of carbon-carbon bonds. In the first part of this thesis, the substrate scope of the rhodium/BINAP-catalyzed 1,4-addition of alkenylzirconocenes to cyclic and acyclic enones – already investigated in my own master thesis – was extended, as well as the scope of transferable alkenyl nucleophiles. The inter¬mediate enolates were trapped as TMS enol ethers, or their TBDMS derivatives, respectively. A proof of concept for employing alkenyl titanates and alanates in the rhodium-catalyzed ACA was demonstrated. Furthermore, Grignard reagent-based aryl titanates were tested for the enantioselective transfer of potentially functionalized aryl nucleophiles. In the second part of the thesis, the synthesis of fluorinated cyclohexa-2,5-dieneimines and their application in copper/phosphoramidite ligand-catalyzed asymmetric 1,4-additions of dialkylzinc reagents was investigated. Having achieved an enantioselective access to cyclohex-2-eneimines, diastereoselective subsequent transformations of the latter were established. These include a second 1,4-addition step of diethylzinc using the same catalytic system, or phenylzinc chloride using the catalytic system rhodium/BINAP, or organocuprates, respectively. The intermediate enamides thus obtained were subjected to a final Noyori transfer hydrogenation step to yield cyclohexylamides in high overall yields. Further diastereoselective transformations of the cyclohex-2-eneimines, e.g. rhodium/BINAP-catalyzed 1,2-addition of phenylzinc chloride, reduction using sodium borohydride and hydrogenation, as well as cyanation and subsequent reduction to a primary amine were successfully achieved.