ASYMMETRIC SYNTHESIS OF SUBSTITUTED PIPERIDINES

A STABLE CHIRAL 1,4-DIHYDROPYRIDINE EQUIVALENT FOR THE ASYMMETRIC SYNTHESIS OF SUBSTITUTED PIPERIDINES ... 

A STABLE CHIRAL 1,4-DIHYDROPYRIDINE EQUIVALENT FOR THE ASYMMETRIC SYNTHESIS OF SUBSTITUTED PIPERIDINES 2-CYANO-6-PHENYLOXAZOLOPIPERIDINE (5H-Oxazolo[3,2-aJpyridine-5-carbonltrlle, hexahydro-3-phenyl-,... 

Bard, A. J., Parsons, R. and Jordan, J., 1985. Standard Potentials in Aqueous Solutions, lUPAC Marcel Dekker, New York, USA Bonin, M., Grierson, D. S., Royer, J. and Husson, H. -P., 1992. A stable chiral 1,4-Dihydropyridine equivalent for the asymmetric synthesis of substituted piperidines 2-Cyano-6-Phenyloxazolopiperidine. Org. Synth. 70, 54-57. 

Synthesis of substituted piperidines Charette and co-workers recently reported a method for the preparation of substituted piperidines from activated pyridines. The method is based on an iridium-catalysed asymmetric hydrogenation of A-Iminopyr-idiniumylides 74 for the synthesis of enantiomerically enriched piperidines 75 [89] (Scheme 12.20). 

Lewis acid-mediated 5N2-type displacement reactions of RMgX have been used for asymmetric synthesis of 2-substituted piperidines,111 and BeCL has been found to promote addition of RLi and RMgX to cyclohex-2-enone.112... 

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>. 

Mitich W (1998) Poison-hemlock (Conium maculatum L.). Weed Technol 12 194—197 Moody CJ, Lightfoot AP, Gallagher PT (1997) Asymmetric synthesis of 2-substituted piperidines. Synthesis of the alkaloids (—)-coniine and ( )-pseudoconhydrine. J Org Chem 62 746-748... 

In addition, silver-catalyzed asymmetric aza-Diels-Alder reactions provide a useful route to optically active nitrogen-heterocyclic compounds such as piperidines or pyrid-azines. Substituted dihydrobenzofurans can also be enantioselectively prepared through silver-promoted allylation of aldehydes. Other types of silver-mediated cyclizations can also be used in the synthesis of tetrahydrofnrans, tetrahydropyrans, 1,2-dioxetanes, 1,2-dioxolanes, medium-sized lactones, dihydroisoqninolines, and so on. Silver salts can also be used as cocatalysts with other transition metals. Unique activity was observed for these silver-based systems in several cases. Conseqnently, the use of silver can enrich several available heterocyclization methods, and fnrther developments in the application of chiral silver complexes will hopefnlly appear in the near future. 

Contemporaneously with Waldmann s group, Wang and co-workers described a novel asymmetric [3-1-6] cycloaddition of azomethine ylides with various readily available fulvenes catalyzed by Cu(I)ATF-BiphamPhos for the synthesis of highly substituted piperidines in good yields with excellent stereocmitrol and broad substrate scope (Scheme 30) [53]. Subsequent transformations allow facile access to enantioenriched fused polycyclic piperidine derivatives without loss of diastereo-and enantioselectivity. 

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