Organic Letters
Letter
(5) For selected examples of Ni-catalyzed β-C−H alkenylation of
amides with alkynes, see: (a) Li, M.; Yang, Y.; Zhou, D.; Wan, D.;
You, J. Nickel-Catalyzed Addition-Type Alkenylation of Unactivated,
Aliphatic C−H Bonds with Alkynes: A Concise Route to
Polysubstituted γ-Butyrolactones. Org. Lett. 2015, 17, 2546−2549.
(b) Maity, S.; Agasti, S.; Earsad, A. M.; Hazra, A.; Maiti, D. Nickel-
Catalyzed Insertion of Alkynes and Electron-Deficient Olefins into
Unactivated sp3 C−H Bonds. Chem. - Eur. J. 2015, 21, 11320−11324.
(c) Lin, C.; Chen, Z.; Liu, Z.; Zhang, Y. Nickel-Catalyzed
Stereoselective Alkenylation of C(sp3)−H Bonds with Terminal
Alkynes. Org. Lett. 2017, 19, 850−853.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
■
S
Experimental procedures; spectral data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
ORCID
(6) Xu, Y.; Young, M. C.; Dong, G. Catalytic Coupling between
Unactivated Aliphatic C−H Bonds and Alkynes via a Metal−Hydride
Pathway. J. Am. Chem. Soc. 2017, 139, 5716−5719.
(7) Chen, Y.; Huang, D.; Zhao, Y.; Newhouse, T. R. Allyl-Palladium-
Catalyzed Ketone Dehydrogenation Enables Telescoping with Enone
α,β-Vicinal Difunctionalization. Angew. Chem., Int. Ed. 2017, 56,
8258−8262.
Notes
(8) For selected reviews on alkene functionalization, see: (a) Beller,
M.; Seayad, J.; Tillack, A.; Jiao, H. Catalytic Markovnikov and anti-
Markovnikov Functionalization of Alkenes and Alkynes: Recent
Developments and Trends. Angew. Chem., Int. Ed. 2004, 43, 3368−
3398. (b) McDonald, R. I.; Liu, G.; Stahl, S. S. Palladium(II)-
Catalyzed Alkene Functionalization via Nucleopalladation: Stereo-
chemical Pathways and Enantioselective Catalytic Applications. Chem.
Rev. 2011, 111, 2981−3019. (c) Crossley, S. W. M.; Obradors, C.;
Martinez, R. M.; Shenvi, R. A. Mn-, Fe-, and Co-Catalyzed Radical
Hydrofunctionalizations of Olefins. Chem. Rev. 2016, 116, 8912−
9000.
(9) (a) Huang, Z.; Dong, G. Catalytic Direct β-Arylation of Simple
Ketones with Aryl Iodides. J. Am. Chem. Soc. 2013, 135, 17747−
17750. (b) Huang, Z.; Sam, Q. P.; Dong, G. Palladium-Catalyzed
Direct β-Arylation of Ketones with Diaryliodonium Salts: a
Stoichiometric Heavy Metal-Free and User-Friendly Approach.
Chem. Sci. 2015, 6, 5491−5498. (c) Chen, M.; Liu, F.; Dong, G.
Direct Palladium-Catalyzed β-Arylation of Lactams. Angew. Chem., Int.
Ed. 2018, 57, 3815−3819. (d) Huang, Z.; Dong, G. Palladium-
Catalyzed Redox Cascade for Direct β-Arylation of Ketones.
Tetrahedron 2018, 74, 3253−3265. (e) Wang, C.; Dong, G. Direct
β-Alkylation of Ketones and Aldehydes via Pd-Catalyzed Redox
Cascade. J. Am. Chem. Soc. 2018, 140, 6057−6061.
(10) For recent examples of Pd-catalyzed direct dehydrogenation of
ketones, see: (a) Diao, T.; Stahl, S. S. Synthesis of Cyclic Enones via
Direct Palladium-Catalyzed Aerobic Dehydrogenation of Ketones. J.
Am. Chem. Soc. 2011, 133, 14566−14569. (b) Gao, W.; He, Z.; Qian,
Y.; Zhao, J.; Huang, Y. General Palladium-Catalyzed Aerobic
Dehydrogenation to Generate Double Bonds. Chem. Sci. 2012, 3,
883−886. (c) Diao, T.; Wadzinski, T. J.; Stahl, S. S. Direct Aerobic
α,β-Dehydrogenation of Aldehydes and Ketones with a Pd(TFA)2/
4,5-Diazafluorenone Catalyst. Chem. Sci. 2012, 3, 887−891. (d) Diao,
T.; Pun, D.; Stahl, S. S. Aerobic Dehydrogenation of Cyclohexanone
to Cyclohexenone Catalyzed by Pd(DMSO)2(TFA)2: Evidence for
Ligand-Controlled Chemoselectivity. J. Am. Chem. Soc. 2013, 135,
8205−8212.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank University of Chicago for the research support. Dr.
Xiaoyang Chen from the University of Chicago is thanked for
checking the experiments.
REFERENCES
■
(1) Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH:
Weinheim, 2000.
(2) For recent reviews, see: (a) Huang, Z.; Dong, G. Catalytic C−C
Bond Forming Transformations via Direct β-C−H Functionalization
of Carbonyl Compounds. Tetrahedron Lett. 2014, 55, 5869−5889.
(b) Huang, Z.; Lim, H. N.; Mo, F.; Young, M. C.; Dong, G.
Transition Metal-Catalyzed Ketone-Directed or Mediated C−H
Functionalization. Chem. Soc. Rev. 2015, 44, 7764−7786.
(3) For selected examples of amide-directed β-C−H alkenylation
reactions, see: (a) Wasa, M.; Engle, K. M.; Yu, J.-Q. Pd(II)-Catalyzed
Olefination of sp3 C−H Bonds. J. Am. Chem. Soc. 2010, 132, 3680−
3681. (b) Wasa, M.; Engle, K. M.; Lin, D. W.; Yoo, E. J.; Yu, J.-Q.
Pd(II)-Catalyzed Enantioselective C−H Activation of Cyclopropanes.
J. Am. Chem. Soc. 2011, 133, 19598−19601. (c) Gutekunst, W. R.;
Gianatassio, R.; Baran, P. S. Sequential Csp3−H Arylation and
Olefination: Total Synthesis of the Proposed Structure of
Pipercyclobutanamide A. Angew. Chem., Int. Ed. 2012, 51, 7507−
7510. (d) He, J.; Li, S.; Deng, Y.; Fu, H.; Laforteza, B. N.; Spangler, J.
E.; Homs, A.; Yu, J.-Q. Ligand-Controlled C(sp3)−H Arylation and
Olefination in Synthesis of Unnatural Chiral α-Amino Acids. Science
2014, 343, 1216−1220. (e) Wang, B.; Lu, C.; Zhang, S.-Y.; He, G.;
Nack, W. A.; Chen, G. Palladium-Catalyzed Stereoretentive
Olefination of Unactivated C(sp3)−H Bonds with Vinyl Iodides at
Room Temperature: Synthesis of β-Vinyl α-Amino Acids. Org. Lett.
2014, 16, 6260−6263. (f) Shan, G.; Huang, G.; Rao, Y. Palladium-
Catalyzed Unactivated β-Methylene C(sp3)−H Bond Alkenylation of
Aliphatic Amides and Its Application in a Sequential C(sp3)−H/
C(sp2)−H Bond Alkenylation. Org. Biomol. Chem. 2015, 13, 697−
701. (g) Chapman, L. M.; Beck, J. C.; Wu, L.; Reisman, S. E.
Enantioselective Total Synthesis of (+)-Psiguadial B. J. Am. Chem. Soc.
2016, 138, 9803−9806. (h) Wu, Q.-F.; Wang, X.-B.; Shen, P.-X.; Yu,
J.-Q. Enantioselective C−H Arylation and Vinylation of Cyclobutyl
Carboxylic Amides. ACS Catal. 2018, 8, 2577−2581.
(11) O’Duill, M. L.; Engle, K. M. Protodepalladation as a Strategic
Elementary Step in Catalysis. Synthesis 2018, 50, 4699−4714.
(12) The basic carboxylate ligand could be helpful to promote the
Pd(II) enolate formation by accelerating α-C−H cleavage. For a
related mechanistic study, see ref 10d.
(13) Alkenyl triflates could also be coupled, but they were found to
be less stable, thereby giving a poor mass balance. The following
alkenyl triflate delivered the β-alkenylation product in 17% yield in
the absence of any silver salt.
(4) For selected examples of β-C−H alkenylation of carboxylic acids,
see: (a) Zhuang, Z.; Yu, C.-B.; Chen, G.; Wu, Q.-F.; Hsiao, Y.; Joe, C.
L.; Qiao, J. X.; Poss, M. A.; Yu, J.-Q. Ligand-Enabled β-C(sp3)−H
Olefination of Free Carboxylic Acids. J. Am. Chem. Soc. 2018, 140,
10363−10367. (b) Hu, L.; Shen, P.-X.; Shao, Q.; Hong, K.; Qiao, J.
X.; Yu, J.-Q. PdII-Catalyzed Enantioselective C(sp3)−H Activation/
Cross-Coupling Reactions of Free Carboxylic Acids. Angew. Chem.,
Int. Ed. 2019, 58, 2134−2138.
D
Org. Lett. XXXX, XXX, XXX−XXX