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

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.