Reaction progress analysis: Powerful tool for understanding suzuki-miyaura reaction and control of polychlorobiphenyl impurity

Organic Process Research and Development

Volumn 13, Issue 3, 2009, Pages 420-428

  Kedia, Sandeep B ^a   Mitchell, Mark B ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 66249141625     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op800205x     Document Type: Article

References (18)

1. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
2. Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419.
3. Tsou, T.; Kochi, J. J. Am. Chem. Soc. 1979, 103, 7547.
4. Moreno-Manas, M.; Perez, M.; Pleixats, R. J. Org. Chem. 1996, 61, 2346.
5. Adamo, C.; Amatore, C.; Ciofini, I.; Jutand, A.; Lakmini, H. J. Am. Chem. Soc. 1979, 103, 7547.
6. Smith, G.; Dezeny, G. J. Org. Chem. 1994, 59, 8151.
7. Blackmond, D. Angew. Chem., Int. Ed. 2005, 44, 4302.
8. Blackmond, D. J. Org. Chem. 2006, 71, 4711.
9. Deschamps, N.; Elitzin, V.; Tabet, E. GSK unpublished data.
10. Rawlings, J.; Ekerdt, J. Chemical Reactor Analysis and Design Fundamentals; Nob Hill Publishing Co.: Madison, WI, 2002.
11. IChemExplorer; Reaction Analytics Inc.: Wilmington, DE, 2008; http://www.ichemexplorer.com.
12. GSK in-house training course: Blackmond, D. Kinetics of Organic Catalytic Reactions; GSK Chemical Development: Philadelphia, PA, U.S.A., 2007.
13. At high [A], the [B] is necessarily high since it is in excess.
14. For LC-MS analysis, the catalyst was forced to sit entirely at (I) by omitting aryl boronic acid from the reaction mixture (as described in the text). HPLC analysis shows complete conversion to (I) which when analyzed by ESI LC-MS furnished a peak with MW ) 884, corresponding to [M-OTf]+ for the complex RPd(PPh3)2OTf. The MS also displayed the characteristic isotopomer pattern for a Pd complex. The characterization of an analogous complex by ESI LC-MS during Pd-catalyzed reductive carbonylation has recently been reported, the intermediate also ionizing as [M-X] in this instance (ref 16). Such complexes clearly have significant aqueous stability and survive ESI LC-MS conditions. This is perhaps unsurprising, since for the case of Suzuki reaction, water often accelerates the reaction (as is the case for our reaction), and use of water as the primary solvent is often employed in the literature for this type of coupling (ref 17).
15. Coifini, I. J. Am. Chem. Soc. 2006, 128, 6829.
16. Smith, M. Adv. Synth. Catal. 2005, 347, 647.
17. Beller, M. J. Am. Chem. Soc. 2008, 130, 15549.
18. See for example: Moore, L.; Shaughnessy, K. Org. Lett. 2004, 6, 225.