Enantioselective creation of benzylic quaternary centers still is a continuous challenge to many synthetic organic chemists. Among the existing methods for installation of this type of center, the direct asymmetric a-arylation of carbonyl compounds is very attractive due to the ready availability of the coupling substrates. Herein, we present some new tools to the catalytic asymmetric aarylation of carbonyl compounds that overcame many of the drawbacks posted in previous methods for this type of reaction.Benzylic quaternary centers are widely found in the structure of a considerable number of natural and pharmaceutically important compounds. Possessing either simple or complex molecular architectures ( Figure 1) these compounds still challenge many synthetic organic chemists, especially with respect to the enantioselective creation of those benzylic quaternary centers. 1
Figure 1 Examples of molecules possessing benzylic quaternary centersAmong the emerged methods for installation of this type of center, the direct asymmetric a-arylation of carbonyl compounds is very attractive due to the ready availability of the coupling substrates. Considering the versatility of the carbonyl group, asymmetric a-arylation of carbonyl compounds is not only limited to the creation of the benzylic center a to a carbonyl, but it can also be employed to generate benzylic centers with other functionalities. Two main methods can be outlined as direct and simple tools for the a-arylation of carbonyl compounds: (1) the nucleophilic aromatic substitution between enolates and aryl halides 2 and (2) transition-metal-catalyzed a-arylation of carbonyl compounds. 3 Although both methods can furnish a-arylated carbonyl compounds in a direct fashion, the former suffers many drawbacks such as the requirement of aromatic compounds with good electron-withdrawing substituents (F, NO 2 ). Based on this fact, the later method has become the one of choice for this type of transformation and many different protocols have been described to date. Nevertheless, much effort is still necessary to put this emerging method in a mature position, especially in the field of catalytic asymmetric a-arylation of carbonyl compounds. For example, high enantioselective a-arylation of carbonyl compounds has only been achieved in a very limited number of cases and with specific substrates. Another point is the limitation of those methods to provide only quaternary centers, which brings a challenge when epimerizable tertiary centers containing an aryl group are desirable. Herein, first, we would like to call the attention for this important and versatile emerging area giving an up-to-date overview of these main methods. Second, stimulate new contributions to this field. Third, to present very recent literature results as new tools to the catalytic asymmetric a-arylation of carbonyl compounds that overcame some of the drawbacks posted above.The first three general methods for the direct transitionmetal-catalyzed a-arylation of carbonyl compounds appeared independently in ...