Organometallic Chemistry and Catalysis
Transition metal-catalyzed allylic alkylations
Transitions metal-catalyzed processes are very popular among synthetic chemists and also people from industry. Palladium definitely plays a dominant role, e.g. in allylic alkylations. But also other elements such as rhodium or ruthenium are interesting candidates, showing a different reactivity and selectivity profile. We use these reactions in the syntheses of γ,δ-unsaturated amino acids and peptides via transition metal-catalyzed allylation of chelated amino acid ester enolates. These reactions are not limited to α-amino acids but can also be applied to α-hydroxy acids and /or α-amino ketones. The applications of stannylated allylic substrates allows the synthesis of metallated amino acids derivatives which can be further modified via cross coupling chemistry. Pd-catalyzed alkylation were the key steps in the syntheses of boletin, trapoxin and the modification of the miuraenamides.
Transition metal-catalyzed hydrostannation
The synthesis of stannylated amino acids requires stannylated allylic substrates which can easily be obtained by hydrostannation of propargylic esters. For this reaction a new catalyst MoBI3 was developed, which allows the hydrostannation in high yield and a highly regioselective fashion. The combination of hydrostannation/Stille-coupling found application in the synthesis of tryptophans and the cyclopeptides Keramamide and Mozamide.
Transition metal–catalyzed C-H functionalizations
This modern topic of regio- and chemoselective functionalizations is especially well suited to modify N-methylated amino acids and peptides selectively at the β-position. Compared to the enolate reactions this protocol has the great advantage that the stereogenic α-centre of the amino acid has not to be generated stereoselectively, but can be transferred from a suitable chiral precursor. It is especially suited for the incorporation of aryl substituents and therefore for the synthesis of aromatic amino acids. The protocol found application in the total synthesis of cyclopeptide alkaloids abyssenine A and mucronine E.
In the early 1980´s Donald Matteson reported a highly efficient and smart protocol for the stereoselective generation of C-C bonds based on reactions of boronic esters and chlorocarbenoids. The asymmetric version of this reaction is now known as the Matteson homologation. It allows the stepwise “assembly line-type” build up of substituted carbon chains with a great variability in the substitution pattern, depending on the nucleophiles (C-, O-, N-) used. The protocol is especially suited for the synthesis of polyketides and was used e.g. in the synthesis of Lagunamide A.