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RESEARCH ARTICLE
Contents Vol 68(11)

Photoinduced Cycloadditions in the Diversity-Oriented Synthesis Toolbox: Increasing Complexity with Straightforward Post-Photochemical Modifications

Weston J. Umstead A , Olga A. Mukhina A , N. N. Bhuvan Kumar A and Andrei G. Kutateladze A B
+ Author Affiliations
- Author Affiliations

A Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA.

B Corresponding author. Email: akutatel@du.edu

Australian Journal of Chemistry 68(11) 1672-1681 https://doi.org/10.1071/CH15266
Submitted: 12 May 2015  Accepted: 28 May 2015   Published: 24 July 2015

Abstract

Rapid growth of complexity and unprecedented molecular architectures is realised via the excited state intramolecular proton transfer (ESIPT) in o-acylamidobenzaldehydes and ketones followed by [4+2] or [4+4] cycloadditions with subsequent post-photochemical modifications. The approach is congruent with diversity-oriented synthesis, whereby photoprecursors are synthesised in a modular fashion allowing for up to four diversity inputs. The complexity of the primary photoproducts is further enhanced using straightforward and high-yielding post-photochemical modification steps such as reactions with nitrile oxides and nitrones, and Povarov and oxa-Diels–Alder reactions.


References

[1]  In 2013 the R&D spending in the US pharmaceutical industry totalled $51.1 billion, the financial support for the medical research by NIH made another $30.3 billion. http://www.nih.gov/about/budget.htm, http://www.statista.com/study/10708/us-pharmaceutical-industry-statista-dossier/.

[2]  CAS statistical summary 1907–2007.

[3]  W. P. Walters, J. Green, J. R. Weiss, M. A. Murcko, J. Med. Chem. 2011, 54, 6405.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFWjsr7O&md5=8c53ac2216d94be4f6ec83466d1926c4CAS | 21755928PubMed |

[4]  (a) T. W. J. Cooper, I. B. Campbell, S. J. F. Macdonald, Angew. Chem., Int. Ed. 2010, 49, 8082.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlalu7%2FE&md5=b289ffefd903f7a925998084bf53bb3aCAS |
      (b) S. D. Roughley, A. M. Jordan, J. Med. Chem. 2011, 54, 3451.
         | Crossref | GoogleScholarGoogle Scholar |

[5]  C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113, 5322.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXktFKgtLc%3D&md5=fb9aeb5d738238f16f1a34060bbc4989CAS | 23509883PubMed |

[6]  (a) For recent examples of significant increase in complexity as a result of a photochemical step followed by post-photochemical transformations, see P. B. Finn, S. Kulyk, S. McN. Sieburth, Tetrahedron Lett. 2015, 56, 3567.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXjtVSrs7Y%3D&md5=5f40f50943c5f4f0cfb82cb808af08b4CAS |
      (b) P. Chen, P. J. Carroll, S. McN. Sieburth, Org. Lett. 2010, 12, 4510.
         | Crossref | GoogleScholarGoogle Scholar |

[7]  (a) O. A. Mukhina, N. N. B. Kumar, T. M. Arisco, R. A. Valiulin, G. A. Metzel, A. G. Kutateladze, Angew. Chem., Int. Ed. 2011, 50, 9423.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFSltbrN&md5=61cb183635cc8913d88bb4528b2b15f7CAS |
      (b) N. S. Nandurkar, N. N. B. Kumar, O. A. Mukhina, A. G. Kutateladze, ACS Comb. Sci. 2013, 15, 73.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) N. N. B. Kumar, O. A. Mukhina, A. G. Kutateladze, J. Am. Chem. Soc. 2013, 135, 9608.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) W. C. Cronk, O. A. Mukhina, A. G. Kutateladze, J. Org. Chem. 2014, 79, 1235.
         | Crossref | GoogleScholarGoogle Scholar |
      (e) N. N. B. Kumar, D. M. Kuznetsov, A. G. Kutateladze, Org. Lett. 2015, 17, 438.
         | Crossref | GoogleScholarGoogle Scholar |
      (f) O. A. Mukhina, N. N. B. Kumar, T. M. Cowger, A. G. Kutateladze, J. Org. Chem. 2014, 79, 10956.
         | Crossref | GoogleScholarGoogle Scholar |
      (g) W. J. Umstead, O. A. Mukhina, A. G. Kutateladze, Eur. J. Org. Chem. 2015, 2205.
         | Crossref | GoogleScholarGoogle Scholar |

[8]  For Lovering’s fsp3 parameter, see F. Lovering, H. Bikker, C. Humblet, J. Med. Chem. 2009, 52, 6752.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht1KjtLvN&md5=d0ce208b94a8f8e1ed5a88658006d537CAS | 19827778PubMed |

[9]  O. A. Mukhina, W. C. Cronk, N. N. B. Kumar, M. Sekhar, A. Samanta, A. G. Kutateladze, J. Phys. Chem. A 2014, 118, 10487.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtVCru77J&md5=256cbd94d92f19b9fabcce8fbdcef8bdCAS | 24958234PubMed |

[10]  Y. Liu, Patent CN101402641 2009.

[11]  D. P. Canterbury, I. R. Herrick, J. Um, K. N. Houk, A. J. Frontier, Tetrahedron 2009, 65, 3165.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjs1agsLw%3D&md5=3cfe5a72d7563cc40f08c2913db9c154CAS | 20161228PubMed |

[12]  Signals for protons Hb and Hc overlap; we assign Ha signal to the doublet in the lowest field.

[13]  Signals for protons Ha and Hb overlap.

[14]  T. S. Snowden, ARKIVOC 2012, 2012, 24.
         | Crossref | GoogleScholarGoogle Scholar |

[15]  E. Borrione, M. Prato, G. Scorrano, M. Stivanello, V. Lucchini, J. Heterocycl. Chem. 1988, 25, 1831.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXksFOmtLc%3D&md5=63d5964a736a417bb4a206a3e83ff5daCAS |

[16]  M. V. Spanedda, V. D. Hoang, B. Croisse, D. Bonnet-Delpon, J.-P. Bégué, Tetrahedron Lett. 2003, 44, 217.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XpsVentb8%3D&md5=6602d9aad371d3fcf7c182da33b6994bCAS |

[17]  R. Stevenson, J. V. Weber, Heterocycles 1988, 27, 1929.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXhtFCmtrk%3D&md5=1a3b6b65927defa44e69c9a1f11d868cCAS |

[18]  (a) A. G. Kutateladze, O. A. Mukhina, J. Org. Chem. 2015, 80, 5218.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXmslWjsrk%3D&md5=749ee00a798639040c05b5166f53def1CAS | 25885091PubMed |
      (b) For the previous version of rff (relativistic force field), see A. G. Kutateladze, O. A. Mukhina, J. Org. Chem. 2014, 79, 8397.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  H.-H. Kuan, C.-H. Chien, K. Chen, Org. Lett. 2013, 15, 2880.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXosFSru7c%3D&md5=2e27309bd28187371bd2401d94f8a6c1CAS | 23718287PubMed |

[20]  Additional NMR experiments: APT, attached proton test; HMBC, heteronuclear multiple-bond correlation; HMQC, heteronuclear multiple-quantum correlation.

[21]  (a) For examples of steps-per-scaffold concept use in the description of combinatorial libraries, see S. Sen, S. R. Kamma, R. Gundla, U. Adepally, S. Kuncha, S. Thirnathi, U. V. Prasad, RSC Adv. 2013, 3, 2404.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtVygurw%3D&md5=87d4001079ad0fe1fc407031c1457b6dCAS |
      (b) M. Díaz-Gavilán, W. R. J. D. Galloway, K. M. G. O’Connell, J. T. Hodgkinson, D. R. Spring, Chem. Commun. 2010, 46, 776.
         | Crossref | GoogleScholarGoogle Scholar |

[22]  (a) D. J. Rogers, T. T. Tanimoto, Science 1960, 132, 1115.
         | Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3cvgvFyntw%3D%3D&md5=81618e37a5bbae4eedd04c5e098194faCAS | 17790723PubMed |
         (b) Open Babel software package http://openbabel.org.

[23]  M. Baker, Nat. Rev. Drug Discovery 2013, 12, 5.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXjtFOi&md5=a49a2a71431fb46e0fca92443e1b2322CAS | 23274457PubMed |

[24]  (a) M. Leirós, J. A. Sanchez, E. Alonso, M. E. Rateb, W. E. Houssen, R. Ebel, M. Jaspars, A. Alfonso, L. M. Botana, Mar. Drugs 2014, 12, 700.
         | Crossref | GoogleScholarGoogle Scholar | 24473170PubMed |
      (b) M. Leirós, J. A. Sanchez, E. Alonso, M. E. Rateb, W. E. Houssen, R. Ebel, M. Jaspars, A. Alfonso, L. M. Botana, Neuropharmacology 2015, 93, 285.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  (a) D. Noutsias, G. Vassilikogiannakis, Org. Lett. 2012, 14, 3565.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XptF2ntbo%3D&md5=944e407a50c027e39ad13afcacd82db5CAS | 22734450PubMed |
      (b) L. Vasamsetty, D. Sahu, B. Ganguly, F. A. Khan, G. Mehta, Tetrahedron 2014, 70, 8488.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  (a) A. K. Ghosh, C.-X. Xu, K. V. Rao, A. Baldridge, J. Agniswamy, Y.-F. Wang, I. T. Weber, M. Aoki, S. G. P. Miguel, M. Amano, H. Mitsuya, ChemMedChem 2010, 5, 1850.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlClu7vM&md5=0e07c46f2b758961c0d17749459162a5CAS | 20827746PubMed |
      (b) A. K. Ghosh, C.-X. Xu, H. L. Osswald, Tetrahedron Lett. 2015, 56, 3314.
         | Crossref | GoogleScholarGoogle Scholar |