Synthesis 2023; 55(13): 1984-1995
DOI: 10.1055/a-2029-0345
psp

Intramolecular Cyclization of N-Propargylic Amides without Transition-Metal Catalysis for Synthesis of Fluoroalkylated Oxazoles: Using Carboxylic Acid Anhydrides as the Fluoroalkyl Source

,
Ryohei Motegi
,
Hideki Amii
We would like to acknowledge the financial support of the Association for the Advancement of Science & Technology, Gunma University, JST CREST Grant Number JP MJCR21L1, and the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 21H01927 Grant-in-Aid for Scientific Research B).


Abstract

Synthesis of 2-fluoroalkylated oxazoles was developed by transition-metal-free intramolecular cyclization of N-propargylic amides, which are prepared from propargylic amines by employing a small excess of commercially available fluorocarboxylic acid anhydrides as fluoroalkyl­ sources, under basic conditions. Oxazoles bearing a trifluoro­methyl, pentafluoroethyl, or heptafluoropropyl group at the C2 position and functional groups on the C4 and/or C5 positions are obtained in moderate to high yields by controlling the reaction conditions.

Supporting Information



Publication History

Received: 19 December 2022

Accepted after revision: 06 February 2023

Accepted Manuscript online:
06 February 2023

Article published online:
13 March 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

    • 1a Hiyama T, Kanie K, Kusumoto T, Morizawa Y, Shimizu M. Organofluorine Compounds: Chemistry and Applications. Springer-Verlag; Berlin: 2000
    • 1b Chambers RD. Fluorine in Organic Chemistry. Blackwell; Oxford: 2004
    • 1c Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications. Wiley-VCH; Weinheim: 2013
    • 1d Meanwell NA. J. Med. Chem. 2018; 61: 5822
    • 1e Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
    • 2a Li JJ. Heterocyclic Chemistry in Drug Discovery. Wiley; Hoboken: 2013
    • 2b Zhang HZ, Zhao ZL, Zhou CH. Eur. J. Med. Chem. 2018; 144: 444
    • 3a Padwa A, Carlsen PH. J, Tremper A. J. Am. Chem. Soc. 1978; 100: 4481
    • 3b Cunico RF, Kuan CP. Tetrahedron Lett. 1990; 31: 1945
    • 3c Wang Y, Zhu S. J. Fluorine Chem. 2000; 103: 139
    • 3d Beatty JW, Douglas JJ, Cole KP, Stephenson CR. J. Nat. Commun. 2015; 6: 1
    • 3e Koshelev VM, Truskanova TD, Cherstkov VF, Romanov DV, Vasili’ev NV. Russ. Chem. Bull. 2005; 54: 1675
    • 3f Shishlyka OS, Shcherbatiuka AV, Iminova RT, Tverdokhlebova AV, Tolmacheva AA, Mykhailiuka PK, Biitsevab AV. J. Fluorine Chem. 2017; 196: 88
    • 3g Sugiishi T, Matsumura C, Amii H. Org. Biomol. Chem. 2020; 18: 3459
    • 4a Jia-Jie W, Zhu Y, Zhan Z. Asian J. Org. Chem. 2012; 1: 108
    • 4b Hachem A, Grée D, Chandrasekhar S, Grée R. Synthesis 2017; 49: 2101
    • 4c Arshadi S, Vessally E, Edjlali L, Ghorbani-Kalhor E, Hosseinzadeh-Khanmiri R. RSC Adv. 2017; 7: 13198
    • 5a Nilsson BM, Hacksell U. J. Heterocycl. Chem. 1989; 26: 269
    • 5b Arcadi A, Cacchi S, Cascia L, Fabrizi G, Marinelli F. Org. Lett. 2001; 3: 2501

    • For reports on the synthesis of oxazoles from N-propargylic amides, see:
    • 5c Hashmi AS. K, Weyrauch JP, Frey W, Bats JW. Org. Lett. 2004; 6: 4391
    • 5d Milton MD, Inada Y, Nishibayashi Y, Uemura S. Chem. Commun. 2004; 2712
    • 5e Zhang L, Xiao K, Qiao Y, Li X, Song C, Chang J. Eur. J. Org. Chem. 2018; 6913
    • 6a Kawamura S, Sodeoka M. Angew. Chem. Int. Ed. 2016; 55: 8740
    • 6b Kawamura S, Dosei K, Valverde E, Ushida K, Sodeoka M. J. Org. Chem. 2017; 82: 12539
    • 6c Valverde E, Kawamura S, Sekine D, Sodeoka M. Chem. Sci. 2018; 9: 7115
  • 7 Xiao F, Yuan S, Huang H, Zhang F, Deng GJ. Org. Lett. 2019; 21: 8533
  • 8 Karuppusamy V, Ilangovan A. Org. Lett. 2020; 22: 7147
  • 9 Motornov V, Beier P. Org. Lett. 2022; 24: 1958
  • 10 Trybulski EJ, Zhang J, Kramss RH, Mangano RM. J. Med. Chem. 1993; 36: 3533
  • 11 For a review on allenamides, see: Lu T, Lu Z, Ma ZX, Zhang Y, Hsung RP. Chem. Rev. 2013; 113: 4862
  • 12 Chachignon H, Scalacci N, Petricci E, Castagnolo D. J. Org. Chem. 2015; 80: 5287
    • 13a Hernando E, Arrayás RG, Carretero JC. Chem. Commun. 2012; 48: 9622
    • 13b Majhail MK, Ylioja PM, Willis MC. Chem. Eur. J. 2016; 22: 7879
  • 14 Trifluoroacetic acid (10 equiv) was used instead of 3 N aq HCl for the synthesis of propargylic amides 1l and 1m.
  • 15 Sinai Á, Vangel D, Gáti T, Bombicz P, Novák Z. Org. Lett. 2015; 17: 4136
  • 16 Song Q.-W, He L.-N. Adv. Synth. Catal. 2016; 358: 1251
  • 17 Brenneman JB, Krall EB, Schlabach M, Wylie AA. WO2020132269A1, 2019
  • 18 Luo B, Weng Z. Chem. Commun. 2018; 54: 10750