4
Tetrahedron
Green Chem. 1999, 1, 69-74; (c) Barbier-Baudry, D.; Dormond, A.; Richard,
We also tested the intramolecular Friedel–Crafts acylations
6c). Unlike a literature report,6a our protocol
S.; Desmurs, J. R. J. Mol. Catal. A: Chem. 2000, 161, 23-29; (d) Fuerstner,
A.; Voigtlaender, D.; Schrader, W.; Giebel, D.; Reetz, M. T. Org. Lett. 2001,
3, 417-420; (e) Anderson, K. W.; Tepe, J. J. Org. Lett. 2002, 4, 459-461; (f)
Duris, F.; Barbier-Baudry, D.; Dormond, A.; Desmurs, J. R.; Bernard, J. M. J.
Mol. Catal. A: Chem. 2002, 188, 97-104; (g) Matsubara, H.; Yasuda, S.; Ryu,
I. Synlett 2003, 247-249; (h) Huang, A.-p.; Liu, X.-y.; Li, L.-h.; Wu, X.-l.;
Liu, W.-m.; Liang, Y.-m. Adv. Synth. Catal. 2004, 346, 599-602; (i) Kangani,
C. O.; Day, B. W. Org. Lett. 2008, 10, 2645-2648; (j) Murphy, B.; Goodrich,
P.; Hardacre, C.; Oelgemoller, M. Green Chem. 2009, 11, 1867-1870; (k)
Wilkinson, M. C. Org. Lett. 2011, 13, 2232-2235; (l) Mahoney, J.; Turnbull,
K.; Cubberley, M. Synth. Commun. 2012, 42, 3220-3229; (m) Perrier, A.;
Keller, M.; Caminade, A.-M.; Majoral, J.-P.; Ouali, A. Green Chem. 2013,
15, 2075-2080; (n) Tran, P. H.; Nguyen, H. T.; Hansen, P. E.; Le, T. N. RSC
Adv. 2016, 6, 37031-37038; (o) Yang, X.; Gao, L.-j.; Chen, P. Guocheng
Gongcheng Xuebao 2016, 16, 522-528.
(Table 5, 6a
–
worked well without extra step to preparing acid anhydrides
or acid halides.
Our protocol worked well in multi-gram scale synthesis
without need for reaction workup (eq-2). Our protocols have
significant advantages over many industrial Friedel–Crafts
acylation operations. As shown in Table 2, our protocol
worked very well in synthesis of 3x for Ibuprofen synthesis,
without the need for use of toxic hydrogen fluoride (Scheme
1b, BHC Ibuprofen synthesis). Compound 3aa (Table 3) is
the key intermediate for production of one of the most
important nonsteroidal anti-inflammatory drug (NSAID) - S-
Naproxen and triple reuptake inhibitor, and the one
industrial synthesis of 3aa is still based on environmentally
unfriendly AlCl3/acid chloride system.10 And pyrrole 3m is
an important industrial intermediate, which synthesis is
based on AlCl3/acid chloride system also.11
3. (a) Vuković, V. D.; Richmond, E.; Wolf, E.; Moran, J. Angew.
Chem. Int. Ed. 2017, 56, 3085-3089; (b) Ji, W.; Liu, Y. A.; Liao, X. Angew.
Chem. Int. Ed. 2016, 55, 13286-13289.
4.
(a) Liu, W.; Wang, H.; Li, C.-J. Org. Lett. 2016, 18, 2184-2187;
(b) Colomer, I.; Batchelor-McAuley, C.; Odell, B.; Donohoe, T. J.; Compton,
R. G. J. Am. Chem. Soc. 2016, 138, 8855–8861; (c) Tian, Y.; Xu, X.; Zhang,
L.; Qu, J. Org. Lett. 2016, 18, 268-271.
5.
chemistry-challenge-1997-greener-synthetic-pathways-award
6. (a) Motiwala, H. F.; Vekariya, R. H.; Aubé, J. Org. Lett. 2015, 17,
5484-5487; (b) Vekariya, R. H.; Aubé, J. Org. Lett. 2016, 18, 3534-3537.
7. (a) Steiner, T. Angew. Chem. Int. Ed. 2002, 41, 48-76; (b) Jeffrey,
G. A. Crystallography Reviews 2003, 9, 135-176; (c) Pihko, P. M., Hydrogen
bonding in organic synthesis. Wiley-VCH: Weinheim, 2009.
8.
J. J.; Taylor, P. J. J. Chem.Soc., Perkin Trans. 2 1989, 699-711.
9. (a) Wilkinson, M. C.; Saez, F.; Hon, W. L. Synlett 2006, 2006,
Abraham, M. H.; Grellier, P. L.; Prior, D. V.; Duce, P. P.; Morris,
In summary, we have developed a metal and halogen-free
Friedel–Crafts acylation protocol with virtually no waste stream
generation enabled by strong hydrogen bond solvent - TFA. Our
methods worked well for carboxylic acid anhydrides/ carboxylic
acids and less reactive aromatics like alkyl substituted benzenes.
1063-1066; (b) Smyth, T. P.; Corby, B. W. J. Org. Chem. 1998, 63, 8946-
8951.
10.
(a) Li, J.; Lv, N.; Jin, H.; Weng, Z.; Zheng, Y. 1-Butyl-2-
hydroxyaralkyl piperazine derivatives useful in the treatment of depress and
preparation. WO2010040315A1, 2010; (b) Zheng, Y.-Y.; Guo, L.; Zhen, X.-
C.; Li, J.-Q. Eur. J. Med. Chem. 2012, 54, 123-136; (c) Zheng, Y.-Y.; Xie, P.;
Xing, L.-X.; Wang, J.-Y.; Li, J.-Q. Org. Process Res. Dev. 2012, 16, 1921-
1926; (d) Weng, Z.; Zheng, Y.; Li, J. Chem. Biol. Drug Des. 2015, 85, 454-
460.
Acknowledgments
We are grateful to the National Science Foundation of China
(NSFC-21672035) and China Recruitment Program of Global
Experts for financial support.
11.
(a) Rokach, J.; Hamel, P.; Kakushima, M.; Smith, G. M.
Tetrahedron Lett. 1981, 22, 4901-4904; (b) He, Y.; Lin, M.; Li, Z.; Liang, X.;
Li, G.; Antilla, J. C. Org. Lett. 2011, 13, 4490-4493; (c) Liu, Z.-d.; Teng, D.-
w. Yingyong Huagong 2013, 42, 860-862.
References and notes
1. Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.;
Leazer, J. J. L.; Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.;
Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9, 411-420.
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2. (a) Baudry-Barbier, D.; Dormond, A.; Duriau-Montagne, F. J.
Mol. Catal. A: Chem. 1999, 149, 215-224; (b) Yadav, G. D.; Pujari, A. A.