Publication Cover
Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 43, 2013 - Issue 5
668
Views
36
CrossRef citations to date
0
Altmetric
Original Articles

Synthesis of Highly Functionalized Piperidines via One-Pot, Five-Component Reactions in the Presence of Acetic Acid Solvent

, , , , &
Pages 635-644 | Received 26 Apr 2011, Published online: 13 Nov 2012

REFERENCES

  • (a) Kleemann , A. , Engel , J. , Kutscher , B. , Reichert , D. , (Eds.). Pharmaceutical Substances ; Stuttgart : Thieme , 1999 ; (b) Rubiralta , M. ; Giralt , E. ; Diez , A. Piperidine: Structure, Preparation, Reactivity and Synthetic Applications of Piperidine and Its Derivatives ; Elsevier : Amsterdam , 1991 ; (c) Weintraub , P. M. ; Sabol , J. S. ; Kane , J. M. ; Borcherding , D. R. Recent advances in the synthesis of piperidones and piperidines. Tetrahedron 2003, 59, 2953–2989 ; (d) Kouznetsov , V. V. Khim.-Farm , Zh. 1991, 25, 61–75, Chem. Abstr. 1991, 115, 158.846 h; (e) Vartanyan , R. S. Khim.-Farm , Zh. 1983, 17, 540–550; Chem. Abstr. 1983, 99, 53629n; (g) Elbein , A. D. ; Molyneux , R. In Alkaloids; Chemical and Biological Perspectives ; Pelletier , S. W. , (Ed.); John Wiley and Sons : New York , 1987 ; vol. 57 , p. 1 ; (h) O'Hagan , D. Pyrrole, pyrrolidine pyridine, piperidine, azepine and tropane alkaloids. Nat. Prod. Rep. 1997, 14, 637–652 ; (i) Felpin , F.-X. ; Lebreton , J. Synthesis of 2,6-dialkyl-1,2,5,6-tetrahydropyridines and their applications in total synthesis. Curr. Org. Synth. 2004, 1, 83–109 ; (d) Watson , P. S. ; Jiang , B. ; Scott , B. A diastereoselective synthesis of 2,4-disubstituted piperidines: Scaffolds for drug discovery. Org. Lett. 2000, 2, 3679–3682 ; (j) Howard , N. ; Abell , C. ; Blakemore , W. ; Chessari , G. ; Congreve , M. ; Howard , S. ; Jhoti , H. ; Murray , C. W. ; Seavers , L. C. A. ; van Montfort , R. L. M. Application of fragment screening and fragment linking to the discovery of novel thrombin inhibitors. J. Med. Chem. 2006, 49, 1346–1355 ; (k) Wright , J. L. ; Gregory , T. F. ; Kesten , S. R. ; Boxer , P. A. ; Serpa , K. A. ; Meltzer , L. T. ; Wise , L. D. Subtype-selective N-methyl-D-aspartate receptor antagonists: Synthesis and biological evaluation of 1-(heteroarylalkynyl)-4-benzylpiperidines. J. Med. Chem. 2000, 43, 3408–3419 .
  • Petit , S. ; Nallet , J. P. ; Guillard , M. ; Dreux , J. ; Chermat , R. ; Poncelet , M. ; Bulach , C. ; Simon , P. ; Fontaine , C. ; Barthelmebs , M. ; Imbs , J. L. Synthèses et activités psychotropes de 3,4-diarylpipéridines: Corrélation structure-activité et recherche d'une activité antihypertensive . Eur. J. Med. Chem. 1991 , 26 , 19 – 32 .
  • Zhou , Y. ; Gregor , V. E. ; Ayida , B. K. ; Winters , G. C. ; Sun , Z. ; Murphy , D. ; Haley , G. ; Bailey , D. ; Froelich , J. M. ; Fish , S. ; Webber , S. E. ; Hermann , T. ; Wall , D. Synthesis and SAR of 3,5-diamino-piperidine derivatives: Novel antibacterial translation inhibitors as aminoglycoside mimetics . Bioorg. Med. Chem. Lett. 2007 , 17 , 1206 – 1210 .
  • Bin , H. ; Crider , A. M. ; Stables , J. P. Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores . Eur. J. Med. Chem. 2001 , 36 , 265 – 286 .
  • Misra , M. ; Pandey , S. K. ; Pandey , V. P. ; Pandey , J. ; Tripathi , R. ; Tripathi , R. P. Organocatalyzed highly atom-economic one-pot synthesis of tetrahydropyridines as antimalarials . Bioorg. Med. Chem. 2009 , 17 , 625 – 633 .
  • (a) Beeler , A. B. ; Gadepalli , R. S. V. S. ; Steyn , S. ; Castagnoli Jr. , N. ; Rimoldi , J. M. Synthesis and in vitro biological evaluation of fluoro-substituted-4-phenyl-1,2,3,6-tetrahydropyridines as monoamine oxidase B substrates . Bioorg. Med. Chem. 2003 , 11 , 5229 – 5234 ; (b) Deskus , J. A. ; Epperson , J. R. ; Charles , P. S. ; Joseph , A. C. ; Dextraze , P. ; Qian-Cutrone , J. ; Gao , Q. ; Ma , B. ; Beno , B. R. ; Mattson , G. K. ; Molski , T. F. ; Krause , R. G. ; Taber , M. T. ; Lodge , N. J. ; Mattson , R. J. Conformationally restricted homotryptamines 3: Indole tetrahydropyridines and cyclohexenylamines as selective serotonin reuptake inhibitors . Bioorg. Med. Chem. Lett. 2007 , 17 , 3099 – 3104 ; (c) Seyfried , C. A. ; Greiner , H. E. ; Haase , A. F. Biochemical and functional studies on EMD 49 980: A potent, selectively presynaptic D-2 dopamine agonist with actions on serotonin systems . Eur. J. Pharmacol. 1989 , 160 , 31 – 41 ; (d) Jaen , J. C. ; Wise , L. D. ; Heffner , T. G. ; Pugsley , T. A. ; Meltzer , L. T. Dopamine autoreceptor agonists as potential antipsychotics, 1: (Aminoalkoxy)anilines . J. Med. Chem. 1988 , 31 , 1621 – 1625 ; (e) Jaen , J. C. ; Caprathe , B. W. ; Wise , L. D. ; Meltzer , L. T. ; Pugsley , T. A. ; Heffner , T. G. Synthesis and pharmacological evaluation of the enantiomers of the dopamine autoreceptor agonist PD 135385 . Bioorg. Med. Chem. Lett. 1993 , 3 , 639 – 644 .
  • Gwaltney II , S. L. ; O'Connor , S.J. ; Nelson , L. T. J. ; Sullivan , G. M. ; Imade , H. ; Wang , W. ; Hasvold , L. ; Li , Q. ; Cohen , J. ; Gu , W.-Z. ; Tahir , S. K. ; Bauch , J. ; Marsh , K. ; Ng , S.-C. ; Frost , D. J. ; Zhang , H. ; Muchmore , S. ; Jakob , C. G. ; Stoll , V. ; Hutchins , C. Aryl tetrahydropyridine inhibitors of farnesyltransferase: Glycine, phenylalanine, and histidine derivatives. Bioorg. Med. Chem. Lett. 2003, 13, 1359–1362.
  • (a) Kamei , K. ; Maeda , N. ; Katsuragi-Ogino , R. ; Koyama , M. ; Nakajima , M. ; Tatsuoka , T. ; Ohno , T. ; Inoue , T. New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects . Bioorg. Med. Chem. Lett. 2005 , 15 , 2990 – 2993 ; (b) Van Voorhis , W. C. ; Rivas , K. L. ; Bendale , P. ; Nallan , L. ; Hornéy , C. ; Barrett , L. K. ; Bauer , K. D. ; Smart , B. P. ; Ankala , S. ; Hucke , O. ; Verlinde , C. L. M. J. ; Chakrabarti , D. ; Strickland , C. ; Yokoyama , K. ; Buckner , F. S. ; Hamilton , A. D. ; Williams , D. K. ; Lombardo , L. J. ; Floyd , D. ; Gelb , M. H. Protein farnesyltransferase inhibitors exhibit potent antimalarial activity . J. Med. Chem. 2005 , 48 , 3704 – 3713 .
  • Von Itzstein , M. ; Wu , W.-Y. ; Kok , G. B. ; Pegg , M. S. ; Dyason , J. C. ; Jin , B. ; Phan , T. V. ; Smythe , M. L. ; White , H. F. ; Oliver , S. W. ; Colman , P. M. ; Varghese , J. N. ; Ryan , D. M. ; Woods , J. M. ; Bethell , R. C. ; Hothman , V. J. ; Camreon , J. M. ; Penn , C. R. Rational design of potent sialidase-based inhibitors of influenza virus replication . Nature 1993 , 363 , 418 – 423 ; (b) Kim , C. U. ; Lew , W. ; Williams , M. A. ; Liu , H. ; Zhang , L. ; Swaminathan , S. ; Bischofberger , N. ; Chen , M. S. ; Mendel , D. B. ; Tai , C. Y. ; Laver , W. G. ; Stevens , R. C. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: Design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity . J. Am. Chem. Soc. 1997 , 119 , 681 – 690 ; (c) Chand , P. ; Kotian , P. L. ; Dehghani , A. ; El-Kattan , Y. ; Lin , T.-H. ; Hutchison , T. L. ; Sudhakar Babu , Y. ; Bantia , S. ; Elliott , A. J. ; Montgomery , J. A. Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity . J. Med. Chem. 2001 , 44 , 4379 – 4392 .
  • (a) Goss , P. E. ; Baker , M. A. ; Carver , J. P. ; Dennis , J. W. Inhibitors of carbohydrate processing: A new class of anticancer agents . Clin. Cancer Res. 1995 , 1 , 935 – 944 ; (b) Nishimura , Y. ; Satoh , T. ; Adachi , H. ; Kondo , S. ; Takeuchi , T. ; Azetaka , M. ; Fukuyasu , H. ; Iizuka , Y. Synthesis and antimetastatic activity of L-iduronic acid–type 1-N-iminosugars . J. Med. Chem. 1997 , 40 , 2626 – 2633 ; (c) Zitzmann , N. ; Mehta , A. S. ; Carrouee , S. ; Butters , T. D. ; Platt , F. M. ; McCauley , J. ; Blumberg , B. S. ; Dwek , R. A. ; Block , T. M. Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus model of hepatitis C virus: Implications for the development of broad spectrum anti-hepatitis virus agents . Proc. Natl. Acad. Sci. U.S.A. 1999 , 96 , 11878 – 11882 .
  • (a) Karlsson , G. B. ; Butters , T. D. ; Dwek , R. A. ; Platt , F. M. Effects of imino sugar N-butyldeoxynojirimycin on the N-glycosylation of recombinant gp120 . J. Biol. Chem. 1993 , 268 , 570 – 576 ; (b) Groopman , J. E. Management of the hematologic complications of human immunodeficiency virus infection . Rev. Infect. Dis. 1990 , 12 , 931 – 937 .
  • (a) Treadway , J. L. ; Mendys , P. ; Hoover , D. J. Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus . Expert Opin. Invest. Drugs 2001 , 10 , 439 – 454 ; (b) Jacob , G. S. Glycosylation inhibitors in biology and medicine . Curr. Opin. Struct. Biol. 1995 , 5 , 605 – 611 .
  • (a) Esquivias , J. ; Arrayas , R. G. ; Carretero , J. C. Catalytic asymmetric inverse-electron-demand Diels−Alder reaction of N-sulfonyl-1-aza-1,3-dienes. J. Am. Chem. Soc. 2007, 129, 1480–1481; (b) Zhu , X.-F. ; Lan , J. ; Kwon , O. An expedient phosphine-catalyzed [4 + 2] annulation: Synthesis of highly functionalized tetrahydropyridines. J. Am. Chem. Soc. 2003, 125, 4716–4717; (c) Takemiya , A. ; Hartwig , J. F. Rhodium-catalyzed intramolecular, anti-Markovnikov hydroamination: Synthesis of 3-arylpiperidines. J. Am. Chem. Soc. 2006, 128, 6042–6043; (d) Amat , M. ; Bassas , O. ; Pericàs , M. A. ; Pasto , M. ; Bosch , J. Highly enantioselective dynamic kinetic resolution and desymmetrization processes by cyclocondensation of chiral aminoalcohols with racemic or prochiral δ-oxoacid derivatives. Chem. Commun. 2005, 1327–1329; (e) Martín , R. ; Murruzzu , C. ; Pericàs , M. A. ; Riera , A. General approach to glycosidase inhibitors: Enantioselective synthesis of deoxymannojirimycin and swainsonine. J. Org. Chem. 2005, 70, 2325–2328.
  • (a) Takasu , K. ; Shindoh , N. ; Tokuyama , H. ; Ihara , M. Catalytic imino Diels–Alder reaction by triflic imide and its application to one-pot synthesis from three components . Tetrahedron 2006 , 62 , 11900 – 11907 ; (b) Sales , M. ; Charette , A. B. Org. Lett. 2005 , 7 , 5773 – 5776 .
  • (a) Murty , M. S. R. ; Ram , R. ; Yadav , J. S. BiCl3-promoted aza-Prins type cyclization: A rapid and efficient synthesis of 2,4-disubstituted piperidines . Tetrahedron Lett. 2008 , 49 , 1141 – 1145 ; (b) Carballo , R. M. ; Ramirez , M. A. ; Rodriguez , M. L. ; Martin , V. S. ; Padron , J. I. Iron(III)-promoted aza-Prins cyclization: Direct synthesis of six-membered azacycles . Org. Lett. 2006 , 8 , 3837 – 3840 ; (c) Dobbs , A. P. ; Guesne , S. J. J. Rapid access to trans-2,6-disubstituted piperidines: Expedient total syntheses of (−)-solenopsin A and (+)-epi-Dihydropinidine . Synlett 2005 , 2101 – 2103 .
  • Fustero , S. ; Jimenez , D. ; Moscardo , J. ; Catalan , S. ; Pozo , C. D. Enantioselective organocatalytic intramolecular aza-michael reaction: A concise synthesis of (+)-sedamine, (+)-allosedamine, and (+)-coniine . Org. Lett. 2007 , 9 , 5283 – 5386 .
  • Davis , F. A. ; Chao , B. ; Rao , A. Intramolecular Mannich reaction in the asymmetric synthesis of polysubstituted piperidines: Concise synthesis of the dendrobate alkaloid (+)-241D and its C-4 epimer . Org. Lett. 2001 , 3 , 3169 – 3171 .
  • Lebold , T. P. ; Leduc , A. B. ; Kerr , M. A. Zn(II)-catalyzed synthesis of piperidines from propargyl amines and cyclopropanes . Org. Lett. 2009 , 11 , 3770 – 3772 .
  • Pégot , B. ; Buu , O. N. V. ; Gori , D. ; Vo-Thanh , G. Asymmetric aza-Diels–Alder reaction of Danishefsky's diene with imines in a chiral reaction medium . Beil. J. Org. Chem. 2006 , 2 , 18 .
  • For some representative reviews, see (a) Benetti , S. ; Romagnoli , R. ; De Risi , C. ; Spalluto , G. ; Zanirato , V. Mastering β-ketoesters . Chem. Rev. 1995 , 95 , 1065 – 1114 ; (b) Langer , P. Regio- and diastereoselective cyclization reactions of free and masked 1,3-dicarbonyl dianions with 1,2-dielectrophiles . Chem. Eur. J. 2001 , 7 , 3858 – 3866 ; (c) Langer , P. Cyclization reactions of 1,3-bis-silyl enol ethers and related masked dianions . Synthesis 2002 , 441 – 459 ; (d) Simon , C. ; Constantieux , T. ; Rodriguez , J. Utilisation of 1,3-dicarbonyl derivatives in multicomponent reactions . Eur. J. Org. Chem. 2004 , 4957 – 4980 .
  • (a) Clarke , P. A. ; Zaytzev , A. V. ; Whitwood , A. C. Pot, atom, and step economic (PASE) synthesis of highly functionalized piperidines: A five-component condensation . Tetrahedron Lett. 2007 , 48 , 5209 – 5212 ; (b) Clarke , P. A. ; Zaytzev , A. V. ; Whitwood , A. C. Pot, atom, and step economic (PASE) synthesis of highly substituted piperidines: A five-component condensation . Synthesis 2008 , 3530 – 3532 .
  • Khan , A. T. ; Parvin , T. ; Choudhury , L. H. Effects of substituents in the β-position of 1,3-dicarbonyl compounds in bromodimethylsulfonium bromide-catalyzed multicomponent reactions: A facile access to functionalized piperidines . J. Org. Chem. 2008 , 73 , 8398 – 8402 .
  • Khan , A. T. ; Lal , M. ; Khan , M. M. Synthesis of highly functionalized piperidines by one-pot multicomponent reaction using tetrabutylammonium tribromide (TBATB). Tetrahedron Lett. 2010, 51, 4419–4424.
  • Khan , A. T. ; Khan , M. M. ; Bannuru , K. K. R. Iodine-catalyzed one-pot five-component reactions for direct synthesis of densely functionalized piperidines . Tetrahedron 2010 , 66 , 7762 – 7772 .
  • For some representative articles, see (a) Delaunay , T. ; Conreaux , D. ; Bossharth , E. ; Desbordes , P. ; Monteiro , N. ; Balme , G. Practical one-pot syntheses of regioisomeric furan-fused pyridinones (and quinolinones) from common precursors . Synthesis 2010 , 1741 – 1744 ; (b) Yang , L.-J. ; Yan , S.-J. ; Chen , W. ; Lin , J. A. Facile route to 1,3-diazaheterocycle-fused[1,2-a]indole derivatives via acetic acid–catalyzed cyclocondensation reactions . Synthesis 2010 , 3536 – 3544 ; (c) Lin , C.-K. ; Lu , T.-J. A simple method for the oxidation of primary alcohols with o-iodoxybenzoic acid (IBX) in the presence of acetic acid . Tetrahedron 2010 , 66 , 9688 – 9693 .

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.