Chiral ligand 2-(2′-piperidinyl)pyridine: synthesis, resolution and application in asymmetric diethylzinc addition to aldehydes

Chiral ligand 2-(2′-piperidinyl)pyridine 1 has been synthesized in good overall yield by sequential benzylation, hydrogenation and debenzylation of 2,2′-bipyridine. Its enantiomerically pure enantiomers have been obtained by resolution of 2-(1-benzyl-2-piperidinyl)pyridine 2 with d-tartaric acid (or l-tartaric acid) followed by debenzylation. The absolute configuration was determined by X-ray analysis of the (S)-2d-tartrate. It was demonstrated that 1 can be used as an effective enantioselective catalyst in the addition of diethylzinc to aldehydes. Optically active secondary alcohols with up to 100% enantiomeric excess were obtained in high yields.

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(S)-2-(1-Benzyl-2-piperidinyl)pyridineC17H20N2[α]D20=-60.5 (c 0.55, ethanol)Absolute configuration: (S)

(S)-2-(2′-Piperidinyl)pyridineC10H14N2[α]D20=-47.0 (c 0.62, ethanol)Absolute configuration: (S)