A diastereoselective synthesis of 2,4-disubstituted piperidines: Scaffolds for drug discovery

Organic Letters

Volumn 2, Issue 23, 2000, Pages 3679-3681

  Watson, Paul S ^a   Jiang, Bin ^a   Scott, Brian ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG; PIPERIDINE DERIVATIVE;

ARTICLE; DRUG DESIGN; OXIDATION REDUCTION REACTION; STEREOISOMERISM; SYNTHESIS;

DRUG DESIGN; OXIDATION-REDUCTION; PHARMACEUTICAL PREPARATIONS; PIPERIDINES; STEREOISOMERISM;

EID: 0034676585     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol006589o     Document Type: Article

References (18)

1. A substructure search of the piperidine ring using the electronic version of the Drug Data Report (MDL Drug Data Report) which includes data from July 1988 through December 1998 revealed over 12 000 discrete piperidine entities that have been mentioned in clinical or preclinical studies.
2. Yamanishi, Y.; Ogura, H.; Kosasa, T. Tanpakushitsu Kakusan Koso 2000, 45 (6), 1047-1051.
3. Yevich, J. P.; Yocca, F. D. Curr. Med. Chem. 1997, 4, 295-312.
4. For sertindole, see: Targum S.; Zborowski, J.; Henry, M.; Schmitz, P.; Sebree, T.; Wallin B. Eur. Neuropsychopharmacol. 1995, 5, 4-71. For resperidone, see: Schotte, A.; Janssen, P. F. M.; Gommeren, W.; Luyten, W. H. M. L.; Van Gompel, P.; Lesage, A. S.; De Loore, K.; Leysen, J. E. Psychopharmacology 1996, 124, 57-73.
5. For sertindole, see: Targum S.; Zborowski, J.; Henry, M.; Schmitz, P.; Sebree, T.; Wallin B. Eur. Neuropsychopharmacol. 1995, 5, 4-71. For resperidone, see: Schotte, A.; Janssen, P. F. M.; Gommeren, W.; Luyten, W. H. M. L.; Van Gompel, P.; Lesage, A. S.; De Loore, K.; Leysen, J. E. Psychopharmacology 1996, 124, 57-73.
6. For two examples that use this control element in an intermolecular fashion, see: (a) Krow, G. R.; Alston, P. V.; Szczepanski, S. W.; Raghavachari, R.; Cannon, K. C.; Carey, J. T. Synth. Comm. 1990, 20(13), 1949-1958.
7. (b) Polniaszek, R. P.; Dillard, L. W. J. Org. Chem. 1992, 57, 4103-4110.
8. Paulson, H.; Todt, K. Angew. Chem., Int. Ed. Engl. 1966, 5 (10), 899-900.
9. Comins, D. L.; Brown, J. D. Tetrahedron Lett. 1986, 27 (38), 4549-4552. An auxiliary-mediated process has also been developed to provide these substrates in optically pure form. See: Comins, D. L.; Goehring, R. R.; Joseph, S. P.; O'Connor, S. J. Org. Chem. 1990, 55, 2574-2576.
10. Comins, D. L.; Brown, J. D. Tetrahedron Lett. 1986, 27 (38), 4549-4552. An auxiliary-mediated process has also been developed to provide these substrates in optically pure form. See: Comins, D. L.; Goehring, R. R.; Joseph, S. P.; O'Connor, S. J. Org. Chem. 1990, 55, 2574-2576.
11. We wish to thank Professor Daniel Comins for making us aware of this reaction.
12. (a) Comins, D. L.; Dehgani, A. Tetrahedron Lett. 1992, 33, 6299-6302.
13. (b) Waldman, H.; Braun, M. J. Org. Chem. 1992, 57, 444.
14. The synthesis and use of this Wittig reagent will be described elsewhere.
15. 1H NMR spectroscopy.
16. The chemical yields of these substrates tended to be lower due to side reactions (amide formation and incomplete ester reduction) associated with the ester functionality.
17. Our work in this area will be disclosed in a separate Letter. For a similar approach to α,β-unsaturated-2-piperidinones, see: Rutjes, F. P. J. T.; Schoemaker, H. E. Tetrahedron Lett. 1997, 38, 677-680.
18. b) confirmed the cis relationship between the substituents.