Publication Cover
Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 38, 2008 - Issue 16
353
Views
7
CrossRef citations to date
0
Altmetric
Original Articles

Fast and Efficient Access to a Family of Multifunctional 1,3,5-Trisubstituted Piperidines

, , &
Pages 2799-2813 | Received 26 Oct 2007, Published online: 25 Aug 2010

REFERENCES

  • (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 ; (b) Wess , G. ; Urmann , M. ; Sickenberger , B. Medicinal chemistry: Challenges and opportunities . Angew. Chem. Int. Ed. 2001 , 40 , 3341 – 3350 ; (c) Muegge , I. Pharmacophore features of potential drugs . Chem. Eur. J. 2002 , 8 , 1976 – 1981 ; (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 .
  • (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 ; (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 ; (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 ; (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 ; (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 ; (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 ; (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 .
  • 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; (b) Groaning, M. D.; Meyers, A. I. Chiral non-racemic bicyclic lactams: Auxiliary-based asymmetric reactions. Tetrahedron 2000, 56, 9843–9873; (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; (d) Rubiralta, M.; Giralt, E.; Diez, A. Piperidine; Elsevier: Amsterdam, 1991; chapters 6–9; (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; (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; (g) Harris, J. M.; Padwa, A. Stereoselective synthesis of 2,5,6-trisubstituted piperidines. Org. Lett. 2002, 4, 2029–2031; (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.
  • (a) Miyaura , N. ; Suzuki , A. Palladium-catalyzed cross-coupling reactions of organoboron compounds . Chem. Rev. 1995 , 95 , 2457 – 2483 ; (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 .
  • (a) Thompson , W. J. ; Gaudino , J. A ; general synthesis of 5-arylnicotinates . J. Org. Chem. 1984 , 49 , 5237 – 5243 : (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 .
  • (a) Jeffery , T. On the efficiency of tetraalkylammonium salts in Heck type reactions . Tetrahedron 1996 , 52 , 10113 – 10130 ; (b) Zim , D. ; Monteiro , A. L. ; Dupont , J. PdCl2 (SEt2)2 and Pd(OAc)2: Simple and efficient catalyst precursors for the Suzuki cross-coupling reaction . Tetrahedron Lett. 2000 , 41 , 8199 – 8202 .
  • 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.
  • 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 .
  • 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 .
  • Ma , D. ; Sun , H. General route to 2,4,5-trisubstituted piperidines from enantiopure β-amino esters: Total synthesis of Pseudodistomin B triacetate and pseudodistomin F . J. Org. Chem. 2000 , 65 , 6009 – 60016 .
  • Low amounts of a dimeric-type urea derivative (5%) were isolated as a by-product 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 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.