Trisubstituted piperidine-derived

A remarkable synthetic route to enamines, based on the reaction of terminal epoxides with hindered lithium amides, has been disclosed by Hodgson and co-workers (2004JA6870). When racemic lithium 2,2,6-trisubstituted piperidine 26 (R = Et) is reacted with terminal epoxides 25, trisubstituted piperidine-derived enamines 27 are formed in yields of up to 83%. The latter exhibited efficient C-alkylation activity toward a... 

Risperidone 118 has been used to treat schizophrenia and bipolar disorder <1997WO042940>. Piperidine derivatives such as panamesine 119, a 1,4,4-trisubstituted piperidine, and preclamol 120, a 1,3-disubstituted piperidine, have also been used as antipsychotic agents . 

Davis, F.A., Zhang, J.Y., Li, Y.X., Xu, H., and DeBrosse, C. (2005) Asymmetric synffiesis of 2,4,5-trisubstituted piperidines from sulfrnimine-derived 6-amino P-ketoesters. Formal synffiesis of pseudodistomin B triacetate, J. Org. Chem., 70, 5413-5419. 

Chiral hydrazones derived from SAMP or RAMP are used in the asymmetric synthesis of 4,5,6-trisubstituted and 6-substituted piperidinones <97LA1115>. Chiral 2-substituted piperidines are prepared by the addition of Grignard reagents to chiral imines followed by oxidation of the terminal double bond and reductive cyclization <97JOC746>. 

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