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. 2018 May 4;20(9):2607-2610.
doi: 10.1021/acs.orglett.8b00813. Epub 2018 Apr 17.

A Strategy to Aminate Pyridines, Diazines, and Pharmaceuticals via Heterocyclic Phosphonium Salts

Chirag Patel  1 , Margaret Mohnike  1 , Michael C Hilton  1 , Andrew McNally  1
Affiliations

A Strategy to Aminate Pyridines, Diazines, and Pharmaceuticals via Heterocyclic Phosphonium Salts

Chirag Patel et al. Org Lett. .

Abstract

A straightforward process to aminate pyridines and diazines is presented by reacting phosphonium salt derivatives with sodium azide. The iminophosphorane products are versatile precursors to several nitrogen-containing functional groups, and the process can be applied to building block heterocycles, to drug-like fragments, and for late-stage functionalization of complex pharmaceuticals. Appealing features of this strategy include using C-H bonds as precursors, precise regioselectivity, and a distinct scope from other amination methods, particularly those relying on halogenated azaarenes.

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Figures

Scheme 1.
Scheme 1.
Derivatizations of iminophosphoranes
Scheme 2.
Scheme 2.
Mechanistic pathways and evidence of an organoazide intermediate.
See this image and copyright information in PMC

References

    1. (a) Lawrence SA Amines: Synthesis, Properties and Applications, Cambridge University Press, 2004.
    2. (b) Corbet J-P; Mignani G Chem. Rev 2006, 106, 2651. - PubMed
    1. (a) Surrey DS; Buchwald SL Angew. Chem. Int. Ed 2008, 47, 6338. - PMC - PubMed
    2. (b) Surrey DS; Buchwald SL Chem. Sci 2011, 2, 27. - PMC - PubMed
    3. (c) Hartwig JF Acc. Chem. Res 2008, 41, 1534. - PMC - PubMed
    4. (d) Ley SV; Thomas AW Angew. Chem. Int. Ed 2003, 42, 5400. - PubMed
    5. (e) Kienle M; Dubbaka SR; Brade K.; Knochel P Eur. J. Org. Chem 2007, 4166. - PubMed
    6. (f) Corcoran EB; Pirnot MT; Lin S; Dreher SD; DiRocco DA; Davies IW; Buchwald SL; MacMillan DWC Science 2016, 353, 279. - PMC - PubMed
    7. (g) Li C; Kawamata Y; Nakamura H; Vantourout JC; Liu Z; Hou Q; Bao D; Starr JT; Chen J; Yian M; Baran PS Angew. Chem. Int. Ed 2017, 56, 13088. - PMC - PubMed
    8. (h) Tasker SZ; Standley EA; Jamison TF Nature 2017, 509, 299. - PMC - PubMed
    9. (i) Ge S; Green RA; Hartwig JF J. Am. Chem. Soc 2014, 136, 1617. - PMC - PubMed
    10. (j) Shin K; Kim H; Chang S Acc. Chem. Res 2015, 48, 1040. - PubMed
    1. Selected examples of radical-based methods: (a) Foo K; Sella E; Thomé I; Eastgate MD; Baran PS J. Am. Chem. Soc 2014, 136, 5279. - PMC - PubMed
    2. (b) Romero NA; Margrey KA; Tay NE; Nicewicz DA Science 2015, 349, 1326. - PubMed
    3. (c) Allen LJ; Cabrera PJ; Lee M; Sanford MS J. Am. Chem. Soc 2014, 136, 5607. - PMC - PubMed
    1. (a) Kattamuri PV; Yin J; Siriwongsup S; Kwon D-Y; Ess DH; Li Q; Li G; Yousufuddin M; Richardson PF; Sutton SC; Kürti L J. Am. Chem. Soc 2017, 139, 11184. - PubMed
    2. (b) Zhou Z; Ma Z; Behnke NE; Gao H; Kürti L J. Am. Chem. Soc 2017, 139, 115. - PMC - PubMed
    3. (c) Paudyal MP; Adbesin AM; Burt SR; Ess DH; Ma Z; Kürti L; Falck JR Science, 2016, 353, 1144. - PMC - PubMed
    4. (d) Kim HJ; Kim J; Cho SH; Chang S, S. J. Am. Chem. Soc 2011, 133, 16382. - PubMed
    5. (e) Yan X; Yang X; Xi C Catal. Sci. Technol 2014, 4, 4169.
    1. (a) Gui J; Pan C-M; Jin Y; Qin T; Lo JC; Lee BJ; Spergel SH; Mertzman ME; Pitts WJ; La Cruz TE; Schmidt MA; Darvatkar N; Natarajan WR; Baran PS Science, 2015, 348, 886. - PubMed
    2. (b) Cheung CW; Hu X Nat. Commun 2016, 7, 1.

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