ACS Catalysis
Research Article
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(4) (a) Florentino, L.; Aznar, F.; Valdes, C. Synthesis of (Z)-N-
Alkenylazoles and Pyrroloisoquinolines from α-N-Azoleketones
Through Pd-Catalyzed Tosylhydrazone Cross-Couplings. Chem. -
Eur. J. 2013, 19, 10506−10510. (b) Peng, J.; Gao, Y.; Zhu, C.; Liu, B.;
Gao, Y.; Hu, M.; Wu, W.; Jiang, H. Synthesis of Polysubstituted 3-
Amino Pyrroles via Palladium-Catalyzed Multicomponent Reaction. J.
Org. Chem. 2017, 82, 3581−3588. (c) Bzeih, T.; Zhang, K.; Khalaf, A.;
Hachem, A.; Alami, M.; Hamze, A. One-Pot Reaction Between N-
Tosylhydrazones and 2-Nitrobenzyl Bromide: Route to NH-Free C2-
Arylindoles. J. Org. Chem. 2019, 84, 228−238. (d) Messaoudi, S.;
Additionally, we have also demonstrated expansion of the
scope of diazo reagents applicable in this chemistry to include
nonstabilized α-aryl diazo compounds by the safe, continuous
on-demand flow generation of the diazo species. We anticipate
these two strategies to allow more broad application of this
diazo cross-coupling chemistry for 1,1-substituted olefin
synthesis. The strategy of diazo slow addition should further
be applicable to any diazo cross-coupling reaction suffering
from poor yield due to background diazo decomposition rates
faster than catalyst turnover and therefore should allow access
to a much greater range of aryl (pseudo)halides for a variety of
diazo coupling reactions in the future.
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Treguier, B.; Hamze, A.; Provot, O.; Peyrat, J.-F.; De Losada, J. R.;
Liu, J.-M.; Bignon, J.; Wdzieczak-Bakala, J.; Thoret, S.; Dubois, J.;
Brion, J.-D.; Alami, M. Isocombretastatins A Versus Combretastatins
A: The Forgotten isoCA-4 Isomer as a Highly Promising Cytotoxic
and Antitubulin Agent. J. Med. Chem. 2009, 52, 4538−4542.
(e) Rasolofonjatovo, E.; Provot, O.; Hamze, A.; Rodrigo, J.;
Bignon, J.; Wdzieczak-Bakala, J.; Lenoir, C.; Desravines, D.; Dubois,
J.; Brion, J.-D.; Alami, M. Design, Synthesis and Anticancer Properties
of 5-Arylbenzoxepins as Conformationally Restricted Isocombretasta-
tin A-4 Analogs. Eur. J. Med. Chem. 2013, 62, 28−39. (f) Soussi, M.
A.; Provot, O.; Bernadat, G.; Bignon, J.; Desravines, D.; Dubois, J.;
Brion, J. D.; Messaoudi, S.; Alami, M. IsoCombretaQuinazolines:
Potent Cytotoxic Agents with Antitubulin Activity. ChemMedChem
2015, 10, 1392−1402. (g) Wang, J.-L.; Li, H.-J.; Wu, Y.-C. Divergent
Synthesis of Marine Natural Products Siphonodictyal B, Coralli-
dictyals C/D, and Liphagal Based on the Early Presence of an
Aldehyde Group Instead of a Late-Stage Introduction. J. Org. Chem.
2018, 83, 8716−8723. (h) Perez Encabo, A.; Turiel Hernandez, J. A.;
Gallo Nieto, F. J.; Lorente Bonde-Larsen, A.; Sandoval Rodriguez, C.
M. Synthesis of Abiraterone and Related Compounds. WO Patent
WO2013/030410 A2, Mar 07, 2013.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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S
Experimental details, select optimization data, character-
ization data for organic molecules, computational details,
and coordinates of calculated structures (PDF)
AUTHOR INFORMATION
Corresponding Author
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ORCID
Notes
The authors declare no competing financial interest.
(5) Greenman, K. L.; Carter, D. S.; Van Vranken, D. L. Palladium-
Catalyzed Insertion Reactions of Trimethylsilyldiazomethane. Tetra-
hedron 2001, 57, 5219−5225.
ACKNOWLEDGMENTS
(6) Peng, C.; Cheng, J.; Wang, J. Palladium-Catalyzed Cross-
Coupling of Aryl or Vinyl Iodides with Ethyl Diazoacetate. J. Am.
Chem. Soc. 2007, 129, 8708−8709.
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Financial support for this work was provided by the University
of Ottawa, the National Science and Engineering Research
Council of Canada (NSERC), and the Canada Research Chair
program. The Canadian Foundation for Innovation (CFI) and
the Ontario Ministry of Economic Development and
Innovation are thanked for essential infrastructure. R.J.S.
thanks NSERC for a CGS-D award.
(7) Zhang, Y.; Wang, J. Recent Developments in Pd-Catalyzed
Reactions of Diazo Compounds. Eur. J. Org. Chem. 2011, 2011,
1015−1026.
(8) Devine, S. K. J.; Van Vranken, D. L. Palladium-Catalyzed
Carbene Insertion into Vinyl Halides and Trapping with Amines. Org.
Lett. 2007, 9, 2047−2049.
(9) (a) Yu, W.-Y.; Tsoi, Y.-T.; Zhou, Z.; Chan, A. S. C. Palladium-
Catalyzed Cross Coupling Reaction of Benzyl Bromides with
Diazoesters for Stereoselective Synthesis of (E)-α,β-Diarylacrylates.
Org. Lett. 2009, 11, 469−472. (b) Chen, S.; Wang, J. Palladium-
Catalyzed Reaction of Allyl Halides with α-Diazocarbonyl Com-
pounds. Chem. Commun. 2008, 4198−4200. (c) Greenman, K. L.;
Van Vranken, D. L. Palladium-Catalyzed Carbene Insertion into
Benzyl Bromides. Tetrahedron 2005, 61, 6438−6441.
REFERENCES
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́
(1) Barluenga, J.; Moriel, P.; Valdes, C.; Aznar, F. N-
Tosylhydrazones as Reagents for Cross-Coupling Reactions: A
Route to Polysubstituted Olefins. Angew. Chem., Int. Ed. 2007, 46,
5587−5590.
(2) (a) Faulkner, D. J. Stereoselective Synthesis of Trisubstituted
Olefins. Synthesis 1971, 1971, 175−189. (b) Reucroft, J.; Sammes, P.
G. Stereoselective and Stereospecific Olefin Synthesis. Q. Rev., Chem.
Soc. 1971, 25, 135−169. (c) Flynn, A. B.; Ogilvie, W. W.
Stereocontrolled Synthesis of Tetrasubstituted Olefins. Chem. Rev.
2007, 107, 4698−4745. (d) Kapat, A.; Sperger, T.; Guven, S.;
Schoenebeck, F. E-Olefins Through Intramolecular Radical Reloca-
tion. Science 2019, 363, 391−396. (e) Naret, T.; Khelifi, I.; Provot, O.;
Bignon, J.; Levaique, H.; Dubois, J.; Souce, M.; Kasselouri, A.;
Deroussent, A.; Paci, A.; Varela, P. F.; Gigant, B.; Alami, M.; Hamze,
A. 1,1-Diheterocyclic Ethylenes Derived from Quinaldine and
Carbazole as New Tubulin-Polymerization Inhibitors: Synthesis,
Metabolism, and Biological Evaluation. J. Med. Chem. 2019, 62,
1902−1916.
(10) Zhang, Z.; Liu, Y.; Gong, M.; Zhao, X.; Zhang, Y.; Wang, J.
Palladium-Catalyzed Carbonylation/Acyl Migratory Insertion Se-
quence. Angew. Chem., Int. Ed. 2010, 49, 1139−1142.
(11) Peng, C.; Yan, G.; Wang, Y.; Jiang, Y.; Zhang, Y.; Wang, J.
Palladium-Catalyzed Coupling Reaction of α-Diazocarbonyl Com-
pounds with Aromatic Boronic Acids or Halides. Synthesis 2010,
2010, 4154−4168.
(12) Barrios-Landeros, F.; Hartwig, J. F. Distinct Mechanisms for the
Oxidative Addition of Chloro-, Bromo-, and Iodoarenes to a
Bisphosphine Palladium(0) Complex with Hindered Ligands. J. Am.
Chem. Soc. 2005, 127, 6944−6945.
(13) (a) Bamford, W. R.; Stevens, T. S. 924. The Decomposition of
Toluene-p-Sulphonylhydrazones by Alkali. J. Chem. Soc. 1952, 4735−
4740. (b) Shapiro, R. H.; Heath, M. J. Tosylhydrazones. V. Reaction
of Tosylhydrazones with Alkyllithium Reagents. A New Olefin
Synthesis. J. Am. Chem. Soc. 1967, 89, 5734−5735. (c) Adlington,
R. M.; Barrett, A. G. M. Recent Applications of the Shapiro Reaction.
Acc. Chem. Res. 1983, 16, 55−59.
(3) Beletskaya, I. P.; Cheprakov, A. V. The Heck Reaction as a
Sharpening Stone of Palladium Catalysis. Chem. Rev. 2000, 100,
3009−3066. (b) Nilsson, P.; Olofsson, K.; Larhed, M. Focus on
Regioselectivity and Product Outcome in Organic Synthesis. In The
Mizoroki−Heck Reaction; Oestreich, M., Ed.; John Wiley & Sons, Ltd.:
West Sussex, 2009; p 133−157.
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ACS Catal. 2019, 9, 5623−5630