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

Prof. Bernhard Breit Ph.D. at University of Kaiserslautern in 1993 Post-doctoral studies with Trost at Standford 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.

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

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

Allenes

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, Brummond, K.M.; Kerekes, A.D.; Wan, H., J. Org. Chem., 2002, 67,

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

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

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

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

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. CO 2 can be eliminated as a traceless directing group.

Optimization of reaction conditions

Scope of regioselective synthesis of tertiary carbon centers

Scope of regioselective synthesis of quaternary carbon centers

Diallylation of acetone-1,3-dicarboxylic acid

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

Proposed mechanism

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.