Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Organic Synthesis
  4. Fast Track Articles
  5. Fast Track Article
image of Metal- and Photocatalyst-Free Sulfonylcyanation of [1.1.1]Propellane with Sulfonyl Cyanide

Abstract

Background

Bicyclo[1.1.1]pentanes (BCPs), recognized as bioisosteres for para-disubstituted benzene rings, have gained prominence as valuable bioactive scaffolds in drug research.

Methods

This study describes a radical-coupling method for the synthesis of sulfonyl-, cyano-substituted BCPs from sulfonyl cyanide and [1.1.1]propellane. In this study, the synthetic schemes were designed to show the chemical reactions. Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) were used to identify and characterize the final compounds.

Results

This method does not require photocatalysts, metals, or light, generating BCP nitriles as a useful building block. The synthetic potential of this mild protocol was showcased by the diverse transformations.

Conclusion

This versatile method significantly expands the range of BCP-type bioisosteres that can be generated.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cos/10.2174/0115701794347153241107110324
2024-11-14
2025-03-01

  • From This Site

    /content/journals/cos/10.2174/0115701794347153241107110324
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. a Stepan A.F. Subramanyam C. Efremov I.V. Dutra J.K. O’Sullivan T.J. DiRico K.J. McDonald W.S. Won A. Dorff P.H. Nolan C.E. Becker S.L. Pustilnik L.R. Riddell D.R. Kauffman G.W. Kormos B.L. Zhang L. Lu Y. Capetta S.H. Green M.E. Karki K. Sibley E. Atchison K.P. Hallgren A.J. Oborski C.E. Robshaw A.E. Sneed B. O’Donnell C.J. Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active γ-secretase inhibitor. J. Med. Chem. 2012 55 7 3414 3424 10.1021/jm300094u 22420884
    [Google Scholar]
  2. b Auberson Y.P. Brocklehurst C. Furegati M. Fessard T.C. Koch G. Decker A. La Vecchia L. Briard E. Improving non-specific binding and solubility: Bicycloalkyls and cubanes as p-phenyl bioisosteres. ChemMedChem 2017 12 8 590 598 10.1002/cmdc.201700082 28319646
    [Google Scholar]
  3. Shire B.R. Anderson E.A. Conquering the synthesis and functionalization of bicyclo[1.1.1]pentanes. JACS Au 2023 3 6 1539 1553 10.1021/jacsau.3c00014 37388694
    [Google Scholar]
  4. a Yu I.F. Manske J.L. Diéguez-Vázquez A. Misale A. Pashenko A.E. Mykhailiuk P.K. Ryabukhin S.V. Volochnyuk D.M. Hartwig J.F. Catalytic undirected borylation of tertiary C–H bonds in bicyclo[1.1.1]pentanes and bicyclo[2.1.1]hexanes. Nat. Chem. 2023 15 5 685 693 10.1038/s41557‑023‑01159‑4 36973434
    [Google Scholar]
  5. b He F.S. Xie S. Yao Y. Wu J. Recent advances in the applications of [1.1.1]propellane in organic synthesis. Chin. Chem. Lett. 2020 31 12 3065 3072 10.1016/j.cclet.2020.04.023
    [Google Scholar]
  6. c Mykhailiuk P.K. Mykhailiuk P.K. Saturated bioisosteres of benzene: Where to go next? Org. Biomol. Chem. 2019 17 11 2839 2849 10.1039/C8OB02812E 30672560
    [Google Scholar]
  7. Gianatassio R. Lopchuk J.M. Wang J. Pan C.M. Malins L.R. Prieto L. Brandt T.A. Collins M.R. Gallego G.M. Sach N.W. Spangler J.E. Zhu H. Zhu J. Baran P.S. Strain-release amination. Science 2016 351 6270 241 246 10.1126/science.aad6252 26816372
    [Google Scholar]
  8. a Makarov I.S. Brocklehurst C.E. Karaghiosoff K. Koch G. Knochel P. Synthesis of bicyclo[1.1.1]pentane bioisosteres of internal alkynes and para‐disubstituted benzenes from [1.1.1]propellane. Angew. Chem. Int. Ed. 2017 56 41 12774 12777 10.1002/anie.201706799 28786520
    [Google Scholar]
  9. b Schwärzer K. Zipse H. Karaghiosoff K. Knochel P. Highly regioselective addition of allylic zinc halides and various zinc enolates to [1.1.1]propellane. Angew. Chem. Int. Ed. 2020 59 45 20235 20241 10.1002/anie.202009340 32744419
    [Google Scholar]
  10. a Alvarez E.M. Bai Z. Pandit S. Frank N. Torkowski L. Ritter T. O-, N- and C-bicyclopentylation using thianthrenium reagents. Nat. Synth. 2023 2 6 548 556 10.1038/s44160‑023‑00277‑8
    [Google Scholar]
  11. b Bai Z. Lansbergen B. Ritter T. Bicyclopentylation of alcohols with thianthrenium reagents. J. Am. Chem. Soc. 2023 145 48 25954 25961 10.1021/jacs.3c10024 38010346
    [Google Scholar]
  12. a Nugent J. Shire B.R. Caputo D.F.J. Pickford H.D. Nightingale F. Houlsby I.T.T. Mousseau J.J. Anderson E.A. Synthesis of all‐carbon disubstituted bicyclo[1.1.1]pentanes by iron‐catalyzed kumada cross‐coupling. Angew. Chem. Int. Ed. 2020 59 29 11866 11870 10.1002/anie.202004090 32346946
    [Google Scholar]
  13. b Pickford H.D. Nugent J. Owen B. Mousseau J.J. Smith R.C. Anderson E.A. Twofold radical-based synthesis of N, C -difunctionalized bicyclo[1.1.1]pentanes. J. Am. Chem. Soc. 2021 143 26 9729 9736 10.1021/jacs.1c04180 34161076
    [Google Scholar]
  14. c Pickford H.D. Ripenko V. McNamee R. Holovchuk S. Thompson A.L. Smith R.C. Mykhailiuk P.K. Anderson E.A. Rapid and scalable halosulfonylation of strain-release reagents. Angew. Chem. Int. Ed. 2023 62 e202213508 10.1002/anie.202213508
    [Google Scholar]
  15. d Nugent J. Sterling A.J. Frank N. Mousseau J.J. Anderson E.A. Synthesis of α-quaternary bicyclo[1.1.1]pentanes through synergistic organophotoredox and hydrogen atom transfer catalysis. Org. Lett. 2021 23 21 8628 8633 10.1021/acs.orglett.1c03346 34699248
    [Google Scholar]
  16. e Wong M.L.J. Sterling A.J. Mousseau J.J. Duarte F. Anderson E.A. Direct catalytic asymmetric synthesis of α-chiral bicyclo[1.1.1]pentanes. Nat. Commun. 2021 12 1 1644 1653 10.1038/s41467‑021‑21936‑4 33712595
    [Google Scholar]
  17. f Caputo D.F.J. Arroniz C. Dürr A.B. Mousseau J.J. Stepan A.F. Mansfield S.J. Anderson E.A. Synthesis and applications of highly functionalized 1-halo-3-substituted bicyclo[1.1.1]pentanes. Chem. Sci. (Camb.) 2018 9 23 5295 5300 10.1039/C8SC01355A 29997886
    [Google Scholar]
  18. g Nugent J. Arroniz C. Shire B.R. Sterling A.J. Pickford H.D. Wong M.L.J. Mansfield S.J. Caputo D.F.J. Owen B. Mousseau J.J. Duarte F. Anderson E.A. A general route to bicyclo[1.1.1]pentanes through photoredox catalysis. ACS Catal. 2019 9 10 9568 9574 10.1021/acscatal.9b03190
    [Google Scholar]
  19. h Sterling A.J. Dürr A.B. Smith R.C. Anderson E.A. Duarte F. Rationalizing the diverse reactivity of [1.1.1]propellane through σ–π-delocalization. Chem. Sci. (Camb.) 2020 11 19 4895 4903 10.1039/D0SC01386B 34122945
    [Google Scholar]
  20. i McNamee R.E. Thompson A.L. Anderson E.A. Synthesis and applications of polysubstituted bicyclo[1.1.0]butanes. J. Am. Chem. Soc. 2021 143 50 21246 21251 10.1021/jacs.1c11244 34904841
    [Google Scholar]
  21. a Zhang X. Smith R.T. Le C. McCarver S.J. Shireman B.T. Carruthers N.I. MacMillan D.W.C. Copper-mediated synthesis of drug-like bicyclopentanes. Nature 2020 580 7802 220 226 10.1038/s41586‑020‑2060‑z 32066140
    [Google Scholar]
  22. b Garry O.L. Heilmann M. Chen J. Liang Y. Zhang X. Ma X. Yeung C.S. Bennett D.J. MacMillan D.W.C. Rapid access to 2-substituted bicyclo[1.1.1]pentanes. J. Am. Chem. Soc. 2023 145 5 3092 3100 10.1021/jacs.2c12163 36696089
    [Google Scholar]
  23. a Yen-Pon E. Li L. Levitre G. Majhi J. McClain E.J. Voight E.A. Crane E.A. Molander G.A. On-DNA hydroalkylation to introduce diverse bicyclo[1.1.1]pentanes and abundant alkyls via halogen atom transfer. J. Am. Chem. Soc. 2022 144 27 12184 12191 10.1021/jacs.2c03025 35759692
    [Google Scholar]
  24. b Huang W. Keess S. Molander G.A. Dicarbofunctionalization of [1.1.1]propellane enabled by nickel/photoredox dual catalysis: One-step multicomponent strategy for the synthesis of BCP-aryl derivatives. J. Am. Chem. Soc. 2022 144 28 12961 12969 10.1021/jacs.2c05304 35793500
    [Google Scholar]
  25. c Dong W. Yen-Pon E. Li L. Bhattacharjee A. Jolit A. Molander G.A. Exploiting the sp2 character of bicyclo[1.1.1]pentyl radicals in the transition-metal-free multi-component difunctionalization of [1.1.1]propellane. Nat. Chem. 2022 14 9 1068 1077 10.1038/s41557‑022‑00979‑0 35864151
    [Google Scholar]
  26. d Huang W. Keess S. Molander G.A. A general and practical route to functionalized bicyclo[1.1.1]pentane‐heteroaryls enabled by photocatalytic multicomponent heteroarylation of [1.1.1]propellane. Angew. Chem. Int. Ed. 2023 62 24 e202302223 10.1002/anie.202302223 37059692
    [Google Scholar]
  27. e Huang W. Keess S. Molander G.A. One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization. Chem. Sci. (Camb.) 2022 13 40 11936 11942 10.1039/D2SC05100A 36320918
    [Google Scholar]
  28. f Huang W. Zheng Y. Keess S. Molander G.A. A general and modular approach to BCP alkylamines via multicomponent difunctionalization of [1.1.1]propellane. J. Am. Chem. Soc. 2023 145 9 5363 5369 10.1021/jacs.2c13298 36802571
    [Google Scholar]
  29. g Kim S. Oh H. Dong W. Majhi J. Sharique M. Matsuo B. Keess S. Molander G.A. Metal-free photoinduced acylboration of [1.1.1]propellane via energy transfer catalysis. ACS Catal. 2023 13 14 9542 9549 10.1021/acscatal.3c02339
    [Google Scholar]
  30. a Chen M. Cui Y. Chen X. Shang R. Zhang X. C−F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres. Nat. Commun. 2024 15 1 419 429 10.1038/s41467‑023‑44653‑6 38199996
    [Google Scholar]
  31. b Wu Z. Xu Y. Liu J. Wu X. Zhu C. A practical access to fluoroalkylthio(seleno)-functionalized bicyclo[1.1.1]pentanes. Sci. China Chem. 2020 63 8 1025 1029 10.1007/s11426‑020‑9733‑y
    [Google Scholar]
  32. c Zhao X. Shou J.Y. Qing F.L. Iodopentafluorosulfanylation of [1.1.1]propellane and further functionalizations. Sci. China Chem. 2023 66 10 2871 2877 10.1007/s11426‑023‑1715‑2
    [Google Scholar]
  33. Dong W. Keess S. Molander G.A. Nickel-mediated alkyl-, acyl-, and sulfonylcyanation of [1.1.1]propellane. Chem Catalysis 2023 3 5 100608 100620 10.1016/j.checat.2023.100608 37840854
    [Google Scholar]
  34. Della E.W. Taylor D.K. Synthesis of some bridgehead-bridgehead-disubstituted bicyclo[1.1.1]pentanes. J. Org. Chem. 1994 59 11 2986 2996 10.1021/jo00090a015
    [Google Scholar]
  35. Wu Z. Xu Y. Zhang H. Wu X. Zhu C. Radical-mediated sulfonyl alkynylation, allylation, and cyanation of propellane. Chem. Commun. (Camb.) 2021 57 49 6066 6069 10.1039/D1CC02249K 34037006
    [Google Scholar]
  36. a Siemeister G. Lücking U. Wengner A.M. Lienau P. Steinke W. Schatz C. Mumberg D. Ziegelbauer K. BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono- and in combination treatment upon oral application. Mol. Cancer Ther. 2012 11 10 2265 2273 10.1158/1535‑7163.MCT‑12‑0286 22821149
    [Google Scholar]
  37. b Scott K.A. Njardarson J.T. Analysis of US FDA-approved drugs containing sulfur atoms. Top. Curr. Chem. (Cham) 2018 376 1 5 39 10.1007/s41061‑018‑0184‑5 29356979
    [Google Scholar]
  38. c Devendar P. Yang G.F. Sulfur-containing agrochemicals. Top. Curr. Chem. (Cham) 2017 375 6 82 126 10.1007/s41061‑017‑0169‑9 28993992
    [Google Scholar]
  39. a Manolikakes G. Liu N-W. Liang S. Recent advances in the synthesis of sulfones. Synthesis 2016 48 13 1939 1973 10.1055/s‑0035‑1560444
    [Google Scholar]
  40. b Liang S. Hofman K. Friedrich M. Keller J. Manolikakes G. Recent progress and emerging technologies towards a sustainable synthesis of sulfones. ChemSusChem 2021 14 22 4878 4902 10.1002/cssc.202101635 34476903
    [Google Scholar]
  41. Meanwell N.A. Improving drug design: An update on recent applications of efficiency metrics, strategies for replacing problematic elements, and compounds in nontraditional drug space. Chem. Res. Toxicol. 2016 29 4 564 616 10.1021/acs.chemrestox.6b00043 26974882
    [Google Scholar]
  42. a Li F. Liao H. Dong J. Xiong W. Yan Y. Li G. Xue D. Metal- and photocatalyst-free three-component strategy to prepare benzylalcohol-, aldehyde-substituted BCP building blocks. Green Chem. 2024 26 9 5531 5537 10.1039/D4GC01015A
    [Google Scholar]
  43. b Li F. Dong J. Liao H. Dang J. Zhou X. Wang Y. Wang C. Jiang Q. Li G. Xue D. Photoinduced generation of alkyl and phthalimide nitrogen radicals from N-hydroxyphthalimide esters for the synthesis of benzophenone-type bioisosteres. Sci. China Chem. 2024 67 10 3389 3396 10.1007/s11426‑024‑2107‑3
    [Google Scholar]
  44. c Jiang Q. Dong J. Wang C. Li F. Zhou X. Wang Y. Liao H. Dang J. Li G. Xue D. Light-induced, Cs 2 CO 3 promoted c–s cleavage of heteroaryl sulfones for benzyl heteroarylation of [1.1.1]propellane. Org. Lett. 2024 26 29 6230 6235 10.1021/acs.orglett.4c02171 39011564
    [Google Scholar]
  45. d Xiao Y. Dong J. Wang Y. Liao H. Dang J. Li G. Xue D. Photoinduced multicomponent heteroarylation of [1.1.1]propellane with katritzky pyridinium salts. Org. Lett. 2024 26 33 7026 7030 10.1021/acs.orglett.4c02571 39140838
    [Google Scholar]
  46. e Wang Y. Dong J. Li F. Wang C. Zhou X. Jiang Q. Liao H. Dang J. Li G. Xue D. A HAT process of N -pyridyl radical cations for the synthesis of benzophenone-type bioisosteres. Org. Chem. Front. 2024 11 20 5712 5719 10.1039/D4QO01338G
    [Google Scholar]
  47. f Dong J. Xue D. Liao H. Recent advances in the synthesis of bicyclo[3.1.1]heptanes. Synthesis 2024 10.1055/a‑2367‑2244
    [Google Scholar]
  48. a Corpas J. Kim-Lee S.H. Mauleón P. Arrayás R.G. Carretero J.C. Beyond classical sulfone chemistry: Metal- and photocatalytic approaches for C–S bond functionalization of sulfones. Chem. Soc. Rev. 2022 51 15 6774 6823 10.1039/D0CS00535E 35838659
    [Google Scholar]
  49. b Wu Z. Xu Y. Wu X. Zhu C. Synthesis of selenoether and thioether functionalized bicyclo[1.1.1]pentanes. Tetrahedron 2020 76 50 131692 10.1016/j.tet.2020.131692
    [Google Scholar]
  50. c Chu X.Q. Ge D. Cui Y.Y. Shen Z.L. Li C.J. Desulfonylation via radical process: Recent developments in organic synthesis. Chem. Rev. 2021 121 20 12548 12680 10.1021/acs.chemrev.1c00084 34387465
    [Google Scholar]
  51. d Yu J. Wu Z. Zhu C. Efficient docking–migration strategy for selective radical difluoromethylation of alkenes. Angew. Chem. Int. Ed. 2018 57 52 17156 17160 10.1002/anie.201811346 30397991
    [Google Scholar]
  52. e Yu J. Zhang X. Wu X. Liu T. Zhang Z.Q. Wu J. Zhu C. Metal-free radical difunctionalization of ethylene. Chem 2023 9 2 472 482 10.1016/j.chempr.2022.10.020
    [Google Scholar]
  53. f Wang J. Wu X. Cao Z. Zhang X. Wang X. Li J. Zhu C. E‐selective radical difunctionalization of unactivated alkynes: Preparation of functionalized allyl alcohols from aliphatic alkynes. Adv. Sci. (Weinh.) 2024 11 16 2309022 10.1002/advs.202309022 38348551
    [Google Scholar]
  54. g Liu J. Ma J. Wang T. Xue X.S. Zhu C. Radical-Mediated α- tert -Alkylation of Aldehydes by Consecutive 1,4- and 1,3-(Benzo)thiazolyl Migrations. JACS Au 2024 4 6 2108 2114 10.1021/jacsau.4c00322 38938795
    [Google Scholar]
  55. h Zhang H. Wang M. Wu W. Zhu C. Heterocyclization reagents for rapid assembly of N-fused heteroarenes from alkenes. Angew. Chem. Int. Ed. 2021 60 3714 3719 10.1002/anie.202013089 33140527
    [Google Scholar]
  56. i Zhou J. Zhou Q. Pan C.-M. Yabe Y. Burns A.C. Collins M.R. Ornelas M.A. Ishihara Y. Baran P.S. C–H methylation of heteroarenes inspired by radical SAM methyl transferase. J. Am. Chem. Soc. 2014 136 4853 4856 10.1021/ja5007838
    [Google Scholar]
  57. j Jiang Y. Fang W.Y. Rakesh K.P. Qin H.L. Copper-catalyzed mild desulfonylation of vinyl sulfonyl molecules. Org. Chem. Front. 2020 7 13 1696 1702 10.1039/D0QO00468E
    [Google Scholar]
  58. k Merchant R.R. Edwards J.T. Qin T. Kruszyk M.M. Bi C. Che G. Bao D.H. Qiao W. Sun L. Collins M.R. Fadeyi O.O. Gallego G.M. Mousseau J.J. Nuhant P. Baran P.S. Modular radical cross-coupling with sulfones enables access to sp 3-rich (fluoro)alkylated scaffolds. Science 2018 360 6384 75 80 10.1126/science.aar7335 29456201
    [Google Scholar]
  59. l Nambo M. Tahara Y. Yim J.C.H. Yokogawa D. Crudden C.M. Synthesis of quaternary centres by single electron reduction and alkylation of alkylsulfones. Chem. Sci. (Camb.) 2021 12 13 4866 4871 10.1039/D1SC00133G 34168761
    [Google Scholar]
  60. m Rong J. Deng L. Tan P. Ni C. Gu Y. Hu J. Radical fluoroalkylation of isocyanides with fluorinated sulfones by visible‐light photoredox catalysis. Angew. Chem. Int. Ed. 2016 55 8 2743 2747 10.1002/anie.201510533 26797782
    [Google Scholar]
  61. n Josephson B. Fehl C. Isenegger P.G. Nadal S. Wright T.H. Poh A.W.J. Bower B.J. Giltrap A.M. Chen L. Batchelor-McAuley C. Roper G. Arisa O. Sap J.B.I. Kawamura A. Baldwin A.J. Mohammed S. Compton R.G. Gouverneur V. Davis B.G. Light-driven post-translational installation of reactive protein side chains. Nature 2020 585 7826 530 537 10.1038/s41586‑020‑2733‑7 32968259
    [Google Scholar]
  62. o Fu W. Han X. Zhu M. Xu C. Wang Z. Ji B. Hao X.Q. Song M.P. Visible-light-mediated radical oxydifluoromethylation of olefinic amides for the synthesis of CF 2 H-containing heterocycles. Chem. Commun. (Camb.) 2016 52 91 13413 13416 10.1039/C6CC07771D 27790647
    [Google Scholar]
/content/journals/cos/10.2174/0115701794347153241107110324
Loading
Metal- and Photocatalyst-Free Sulfonylcyanation of [1.1.1]Propellane with Sulfonyl Cyanide
Bentham Science Publishers ; https://doi.org/10.2174/0115701794347153241107110324
/content/journals/cos/10.2174/0115701794347153241107110324
/content/journals/cos/10.2174/0115701794347153241107110324
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: Pentanes ; bioisosteres ; sulfonyl cyanide

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test