a meta selective copper- catalyzed c-h bond …ccc.chem.pitt.edu/wipf/current...
TRANSCRIPT
![Page 1: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/1.jpg)
A Meta Selective Copper-Catalyzed C-H Bond Arylation
Robert J. Phipps and Matthew J. Gaunt Science 2009, 323, 1593.
Wipf Group Current Literature Meeting 4-11-09
Marija Manojlović
![Page 2: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/2.jpg)
Electrophillic Aromatic Substitution
Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593.
![Page 3: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/3.jpg)
Indirect meta-substitution Sulfoxide as a relay:
Knochel, P. et al. ACIE 2008, 47, 1503.
Brown, J. M. et al. Org. Biomol. Chem. 2008, 6, 1215.
Metallation using TMP2Mg 2LiCl:
![Page 4: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/4.jpg)
Mechanism of C-H Activation EAS on e--rich arenes
Pd-catalyzed hydroarylation:
Fujiwara, Y. et al. Acc. Chem. Res., 2001, 34, 633.
![Page 5: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/5.jpg)
Mechanism of C-H Activation Concerted metallation-deprotonation on e--poor
and neutral arenes
Fagnou, K.; Lafrance, M. JACS 2006, 128, 16496.
![Page 6: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/6.jpg)
Mechanism of C-H Activation Directed cyclometallation
Ketone directed cyclometallations:
Giri, R.; Yu, J.-Q. JACS 2008, 130, 14082.
Chatani N. et. Al. Nature 1993, 366, 529.
Carboxilate directed cyclometallations:
![Page 7: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/7.jpg)
Mechanism of C-H Activation Directed cyclometallation
Sanford, M. S. et al. JACS 2008, 130, 13285.
![Page 8: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/8.jpg)
Mechanism of C-H Activation Acetanilide directed cyclometallations
Buchwald, S. L. et al. OL 2008, 10, 2207. Shu, Z.-J. et al. Synlett 2008, 949.
![Page 9: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/9.jpg)
Arylation of Indoles
Sanford, M. S. et al. JACS 2006, 128, 4972. Gaunt, M. J. et al. JACS 2008, 130, 8172.
![Page 10: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/10.jpg)
o-Arylation of Acetanilides
Daugulis, O.; Zaitsev, V. G. ACIE, 2005, 44, 4046.
![Page 11: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/11.jpg)
Reaction Optimization and Mechanistic Proposal
Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593.
![Page 12: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/12.jpg)
Substrate Scope
Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593.
![Page 13: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/13.jpg)
Scope of the Aryl Group Transfer
Controlling the Site Selectivity
Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593.
![Page 14: A Meta Selective Copper- Catalyzed C-H Bond …ccc.chem.pitt.edu/wipf/Current Literature/Marija_5.pdfA Meta Selective Copper-Catalyzed C-H Bond Arylation Robert J. Phipps and Matthew](https://reader031.vdocuments.us/reader031/viewer/2022011910/5f77e42fe4dead40af659d52/html5/thumbnails/14.jpg)
Conclusions
• Mild copper-catalyzed highly meta-selective arylation of acylanilides was developed
• Broad range of substrates is compatible with this reaction, though the best results were obtained with electron-rich substrates
• Meta-selectivity can be overridden by strongly electron-donating substituents
• Reaction is proposed to proceed through oxazoline-like intermediate
• Further mechanistic work is ongoing