Rhodium-Catalyzed Chemo- and Regioselective Decarboxylative Addition of β -

1. Rhodium-Catalyzed Chemo- and Regioselective Decarboxylative Addition of β- Ketoacids to Allenes: Efficient Construction of Tertiary and Quaternary Carbons Centers Literature meeting February 19 th 2014 By : Antoine Caron Li C.; Breit B. J.Am.Chem.Soc. 2014, 136, 862−865

2. Ph.D. at University of Kaiserslautern in 1993 • Post-doctoral studies with Trost at Standford • 1999-2001 professor of organic chemistry at University of Heidelberg • Since 2001, holds a chair of organic chemistry at the University of Freiburg His research interests include the developement and exploration of new concepts and methods for organic synthesis and homogeneous catalyst. Prof. Bernhard Breit

3. Background Under certain conditions, transition metals produce branched allylic compounds (right) Trost M.B. ; Fullerton J. T. J. Am. Chem. Soc.1973, 95, 292–294 Liu, W.-B.; Reeves, C. M.; Virgil, S. C.; Stoltz, B. M. J. Am. Chem. Soc. 2013, 135, 10626.

4. Background Koscher, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011, 133, 20746.

5. Allenes

6. Allenes in organic synthesis • Allenes are used in many ways in organic synthesis. These methods are often applied toward • making a natural product. They are used as substrates in many well known transformations: • Diels-Alder reaction • Pausan-Khand cyclization Min, S.-J.; Jung, M.E., J. Am. Chem. Soc., 2005, 127, 10834-10835 Brummond, K.M.; Kerekes, A.D.; Wan, H., J. Org. Chem., 2002, 67, 5156-5163

7. Pd-catalyzed tandem coupling isomerization reaction (CIR) Shen R.; Chen K.; Deng Q.; Yang J.; Zhang L. Org. Lett. ASAP

8. Allenes in natural products As of 2004, around 150 natural products containing allenes were identified Hoffmann-Röder, A.; Krause, N.; Angew. Chem. Int. Ed.; 2004, 43, 1196-1216

9. Synthesis of allene. • Crabbé Homologation and modification. • Nucleophilic attack on alkyne • [2,3] sigmatropic rearrangement Li Z.; Boyarskikh V.; Hansen H. J.; Autschbach J.; Museav G.D.; Davies L. M. H. J.Am.Chem.Soc. 2012, 134, 15497−1550

10. Background Koscher, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011, 133, 20746.

11. This paper • The carboxylic acid may initiate the reaction through the formaton of the allyl-Rh intermediate. • The nucleophilicity of the α carbon would be enhanced. • CO2 can be eliminated as a traceless directing group.

12. Optimization of reaction conditions

13. Scope of regioselective synthesis of tertiary carbon centers

14. Scope of regioselective synthesis of quaternary carbon centers

15. Diallylation of acetone-1,3-dicarboxylic acid

16. Mechanistic studies • 2 questions regarding this mechanism : • Decarboxylation or allylation goes first ? • Inner-sphere or outer-sphere mechanism ?

17. Proposed mechanism

18. Conclusions • They have developed a highly regioselective decarboxylative addition of β-ketoacids to allenes • to give γ-δ-unsaturated ketones. • Quaternary and tertiary carbons centers could be generated in high yield. • A mild and atom economic method was developed. • Milder conditions than the enolate allylation under basic conditions.