Fast and efficient access to a family of multifunctional 1,3,5-trisubstituted piperidines

Synthetic Communications

Volumn 38, Issue 16, 2008, Pages 2799-2813

  Díaz, José Luis ^a   Fernández Forner, Dolors ^b   Bach, Jordi ^b   Lavilla, Rodolfo ^a  

^a INSTITUTE FOR RESEARCH IN BIOMEDICINE   (Spain)

^b Laboratorios Almirall ^*  (Spain)

Author keywords

Piperidines; Protecting groups; Pyridines; Scaffolds; Stereoselective synthesis

Indexed keywords

FUNCTIONAL GROUP; HETEROCYCLIC COMPOUND; NICOTINIC ACID; PIPERIDINE DERIVATIVE;

ARTICLE; CHEMICAL REACTION; STEREOCHEMISTRY; SYNTHESIS;

EID: 49949083696     PISSN: 00397911     EISSN: 15322432     Source Type: Journal    
DOI: 10.1080/00397910701877608     Document Type: Article

References (30)

1. (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. Methods for drug discovery: Development of potent, selective, orally effective cholecystokinin antagonists. J. Med. Chem. 1988, 31, 2235-2246;
2. (b) Wess, G.; Urmann, M.; Sickenberger, B. Medicinal chemistry: Challenges and opportunities. Angew. Chem. Int. Ed. 2001, 40, 3341-3350;
3. (c) Muegge, I. Pharmacophore features of potential drugs. Chem. Eur. J. 2002, 8, 1976-1981;
4. (d) Breinbauer, R.; Vetter, I. R.; Waldmann, H. From protein domains to drug candidates: Natural products as guiding principles in the design and synthesis of compound libraries. Angew. Chem. Int. Ed. 2002, 41, 2878-2890.
5. (a) Lapuyade, G.; Schlewer, G.; N'Goka, V.; Vernieres, J.-C.; Chambon, J.-P.; Lagrange, J.; Lagrange, P.; Wermuth, C. G. Alkyl and aryl derivatives of nipecotic acid: Synthesis and inhibition of GABA uptake as a function of conformational parameters and bioavailability. Eur. J. Med. Chem. 1987, 22, 383-391;
6. (b) Knoops, N.; Deroover, G.; Jidong, Z.; Compernolle, F.; Hoornaert, G. J. Generation of 3-piperidine(methan)amines and cyclic 3-piperidine-methanamines as potential substance P antagonists. Tetrahedron 1997, 53, 12699-12716;
7. (c) Kelly, T. R.; Howard, H. R.; Koe, B. K.; Sarges, R. Synthesis and dopamine autoreceptor activity of a 5-(methylmercapto)-methyl-substituted derivative of (±)-3-PPP [3-(3-hydroxyphenyl)-1-propylpiperidine]. J. Med. Chem. 1985, 28, 1368-1371;
8. (d) Danieli, B.; Lesma, G.; Passarella, D.; Silvani, A. Highly enantiopure C1-symmetric cis-piperidine-3,5-dimethanol monoacetates by enzymic asymmetrization. J. Org. Chem. 1998, 63, 3492-3496;
9. (e) Amat, M.; Escolano, C.; Lozano, O.; Llor, N.; Bosch, J. Enantioselective synthesis of cis- and trans-3,5-disubstituted piperidines: Synthesis of 20S- and 20R-dihydrocleavamine. Org. Lett. 2003, 5, 3139-3142;
10. (f) Lee, M. J.; Lee, K. Y.; Kim, J. N. Synthesis of N-benzyl-3,5- disubstituted piperidines via double Michael addition strategy. Bull. Korean Chem. Soc. 2005, 26, 477-480;
11. (g) Olofsson, B.; Bogár, K.; Fransson, A.-B. L.; Bäckvall, J.-E. Divergent asymmetric synthesis of 3,5-disubstituted piperidines. J. Org. Chem. 2006, 71, 8256-8260.
12. In sharp contrast, efficient synthetic approaches to other piperidine substitution patterns have been reported. Among them: (a) Amat, M.; Pérez, M.; Llor, N.; Bosch, J. Stereodivergent synthesis of enantiopure cis- and trans-3-ethyl-4-piperidineacetates. Org. Lett. 2002, 4, 2787-2790;
13. (b) Groaning, M. D.; Meyers, A. I. Chiral non-racemic bicyclic lactams: Auxiliary-based asymmetric reactions. Tetrahedron 2000, 56, 9843-9873;
14. (c) Comins, D. L.; Joseph, S. P.; Goehring, R. R. Asymmetric synthesis of 2-alkyl(aryl)-2,3-dihydro-4-pyridones by addition of Grignard reagents to chiral 1-acyl-4-methoxypyridinium salts. J. Am. Chem. Soc. 1994, 116, 4719-4728;
15. (d) Rubiralta, M.; Giralt, E.; Diez, A. Piperidine; Elsevier: Amsterdam, 1991; chapters 6-9;
16. (e) Mangeney, P.; Gosmini, R.; Raussou, S.; Commerçon, M.; Alexakis, A. Preparation and utilization of chiral dihydropyridines: Synthesis of chiral indoloquinolizines and benzoquinolizines. J. Org. Chem. 1994, 59, 1877-1888;
17. (f) Guerrier, L.; Royer, J.; Grierson, D. S.; Husson, H.-P. Chiral 1,4-dihydropyridine equivalents: A new approach to the asymmetric synthesis of alkaloids: The enantiospecific synthesis of (+)- and (-)-coniine and dihydropinidine. J. Am. Chem. Soc. 1983, 105, 7754-7755;
18. (g) Harris, J. M.; Padwa, A. Stereoselective synthesis of 2,5,6-trisubstituted piperidines. Org. Lett. 2002, 4, 2029-2031;
19. (h) Watson, P. S.; Jiang, B.; Scott, B. A diastereoselective synthesis of 2,4-disubstituted piperidines: Scaffolds for drug discovery. Org. Lett. 2000, 2, 3679-3681.
20. (a) Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 1995, 95, 2457-2483;
21. (b) Interestingly, heteroarylboronic acids have been employed in this transformation, therefore adding new molecular diversity to the prepared scaffolds. See Chamoin, S.; Houldsworth, S.; Kruse, C. G.; Bakker, W. I.; Snieckus, V. The Suzuki-Miyaura cross coupling reactions on solid support: Link to solution phase directed ortho metalation: The Leznoff acetal linker approach to biaryl and heterobiaryl aldehydes. Tetrahedron Lett. 1998, 39, 4179-4182.
22. (a) Thompson, W. J.; Gaudino, J. A; general synthesis of 5-arylnicotinates. J. Org. Chem. 1984, 49, 5237-5243;
23. (b) A solid-phase approach has been explored for the related Stille coupling with a bromonicotinic ester. See Chamoin, S.; Houldsworth, S.; Snieckus, V. The Stille cross coupling reactions on solid support: Link to solution phase directed ortho metalation: An ester linker approach to styryl, biaryl and heterobiaryl carboxylic acids. Tetrahedron Lett. 1998, 39, 4175-4178.
24. (a) Jeffery, T. On the efficiency of tetraalkylammonium salts in Heck type reactions. Tetrahedron 1996, 52, 10113-10130;
25. 2: Simple and efficient catalyst precursors for the Suzuki cross-coupling reaction. Tetrahedron Lett. 2000, 41, 8199-8202.
26. Neustadt, B. R.; Smith, E. M.; Nechuta, T.; Zhang, Y. Combinatorial libraries based on a novel and readily accessible "centroid" scaffold. Tetrahedron Lett. 1998, 39, 5317-5320.
27. Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J. Med. Chem. 2000, 43, 953-970.
28. Loudon, G. M.; Radhakrishna, A. S.; Almond, M. R.; Blodgett, J. K.; Boutin, R. H. Conversion of aliphatic amides into amines with [I,I-bis(trifluoroacetoxy)iodo]benzene, 1: Scope of the reaction. J. Org. Chem. 1984, 49, 4272-4276.
29. Ma, D.; Sun, H. General route to 2,4,5-trisubstituted piperidines from enantiopure b-amino esters: Total synthesis of Pseudodistomin B triacetate and pseudodistomin F. J. Org. Chem. 2000, 65, 6009-60016.
30. Low amounts of a dimeric-type urea derivative (5%) were isolated as a byproduct in the Curtius rearrangement. For the formation of ureas in these reactions, see Ninomiya, K.; Shioiri, T.; Yamada, S. Phosphorus in organic synthesis, VII: Diphenyl phosphorazidate (DPPA): A new convenient reagent for a modified Curtius reaction. Tetrahedron 1974, 30, 2151-2157.