Cytisine as a scaffold for ortho-diphenylphosphinobenzenecarboxamide ligands for Pd-catalyzed asymmetric allylic alkylation

(-)-Cytisine has been used as a scaffold for the synthesis of three novel phosphino-benzenecarboxamide ligands. The latter were obtained from cytisine and tetrahydrocytisine, and tetrahydrodeoxocytisine thereof. The structures and conformations of the newly prepared compounds were elucidated on the basis of NMR, X-ray and DFT studies. Conformational studies in respect of hindered rotation of the amide group and the flexibility of the piperidine ring were performed. The X-ray structure of the tetrahydrocytisine-derived ligand was in agreement with the conformation in solution. The application of the ligands in Pd-catalyzed asymmetric allylic alkylation of (E)-1,3-diphenyl-2-propenyl acetate proceeded with excellent conversions and ee's of up to 91%. The observed catalytic activity of the three ligands strongly correlated with their conformational behaviour. Additionally, a strong dependence of the enantioselectivity on the applied BSA/base system was observed. (C) 2014 Elsevier B.V. All rights reserved.