Synthesis Of Chiral Tridentate Ligands Embodying The Bispidine Framework And Their Application In The Enantioselective Addition Of Diethylzinc To Aldehydes

3-Alkyl-3,7-diazabicyclo[3.3.1]nonane 4a-4b were conveniently synthesized from N-benzyl-4-piperidinone and amine via double Mannich reaction, followed by Wolff-Kishner reduction and debenzylation through Pd/C catalyzed hydrogenation. Then, compound 4a were emplyed to react with six N-tert-butoxycarbonyl-L-amino acids, followed by deprotection of tert-butoxycarbonyl group, to generate six new chiralα-amino amide ligends embodying the bispidine framework. Compound 4a-4b were also employed to react with (R)-(-)-mandelic acid to give two new chiralα-hydroxy amide ligends with bispidine moiety. All the target compounds and the key intermediates in the synthesis were characterized by FT-IR,1H NMR,13C NMR,and MS.The synthesized ligands were used in the enantioselective addition of diethylzinc to several aromatic aldehydes and an aliphatic aldehyde. High yield and enantioselectivity were received in the cases of aromatic aldehydes as substrates especially when the employed chiral ligand has a hydroxyl group attached to the chiral center. The effect of the structure, the amount of tridentate chiral ligands, solvent and temperature on the enantioselectivity of the addition products were studied. A possible mechanism for the addition of diethylzinc to aldehydes in the presence of bispidine-derived ligands were proposed based upon the catalytic reaction results and referred to the mechanisms proposed for the other reaction systems in literature.