Abstract
A series of amino acid substituted guanidines of general structure I and II (AA = L-Proline, L-alanine and L-phenylalanine derivatives; (R, R1, R2 = H, Me, Alkyl, Aryl, Boc, Cbz) were prepared and their applications in asymmetric Michael reactions investigated. Initially, the project focused on the synthesis a range of N-alkylated-L-proline amides of several guandines. The catalysts prepared were applied to the Michael reaction between 2-nitrostyrene III and quinone IV leading to the conjugate product V in 17-99% yield and up to 56% enantiomeric excess. Hydrazine and several heterocyclic derivatives were also prepared which proved less effective. A series of N,N-dimethyl-L-alanine and N,N-dimethyl-L-phenylalanine derivatives were similarly prepared and these gave enantioselectivities of up to 31% ee in this reaction. The influence of racemisation of these catalysts during CDI coupling was also studied. Finally, N-protected-L-proline, L-alanine and L-phenylalanine derivatives were prepared to counter the observed racemisation and these gave enantioselectivities of up to 26% ee.
X-ray crystallographic structures were determined for several of these compounds and the hydrogen bonding patterns observed were used to speculate on the mechanism of the reaction and the magnitude of the asymmetric induction observed. The X-ray crystallographic results proved that partial racemisation was occurring during the formation of the catalysts in a CDI mediated coupling reaction.