The enantionselective palladium-catalyzed allylic alkylation (Tsuji-Trost reaction),1 an established and versatile method today, suffered from the limitation to 'soft' nucleophiles, and it was questionable whether the method can be extended to 'hard' nucleophiles. After we and others have used nonstabilized enolates of ketones and lactones,2 we report here the diastereoselective and/or enantioselective allylation of doubly deprotonated carboxylic acids3, undoubtly the 'hardest enolates'. Thus, dilithiated a-alkyl- and a-aryl substituted carboxylic acids 1 undergo smooth palladium-catalyzedallylic alkylations in a diastereoselective and enantioselective manner, as exemplified for phenylacetic acid.The presence of LiCl was found to be crucial for reactivity and enantioselectivity. As we felt that stoichiometric amounts of the salt in previous procedures were uneconomical and tedious, we used allylic chlorides that will provide chloride anions in catalytic, but sufficient amount. The protocol was applied in the allylation of the dianion of acetic acid, demonstrating the detour via the 'standard nucleophile' malonate (and subsequent saponification and decarboxylation) might become avoidable. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/63924_acs_spring_2011.jpg' alt='' />More recently, we were able to perform enantioselective allylic alkylations with lithium enolates of (acyclic) carboxylic esters.[1] Reviews: B.M. Trost, M. L. Crawley, Chem. Rev. 2003 , 103, 2921.[2] M.Braun, F. Laicher, T. Meier, Angew. Chem. Int. Ed. 2000 , 39, 3494, M. Braun, T. Meier, Angew. Chem. Int. Ed. 2006 , 45, 6952; M. Braun, T.Meier, F. Laicher, P. Meletis, M. Fidan, Adv. Synth. Catal. 2008 , 350, 303; M. Braun, P. Meletis, M. Fidan, Org. Synth. 2009 , 86, 47; P. Meletis, M. Patil, W. Thiel, W. Frank, M. Braun, Chem. Eur. J. 2011 , 17, 11243.[3] M.Braun, P. Meletis, R.Visse, Adv. Synth. Catal. 2011 , 353, 3380.

Asymmetric allylic alkylation of doubly deprotonated carboxylic acids an ester enolates

248th National Meeting (2014)

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