Copper-Catalyzed Asymmetric Conjugate Addition of Aryl Aluminum Reagents to Trisubstituted Enones: Construction of Aryl-Substituted Quaternary Centers
Copper-Catalyzed Asymmetric Conjugate Addition of Aryl Aluminum Reagents to Trisubstituted Enones: Construction of Aryl-Substituted Quaternary Centers
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DOI：
10.1002/anie.200803436
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Alexakis, Alexandre
中科院分区：
文献类型：
--
作者：
Hawner, Christine;Li, Kangying;Alexakis, Alexandre
In the field of asymmetric conjugate addition (ACA) to enones, much effort has been directed towards the development of copper-and rhodium-catalyzed reactions of alkylmetal as well as aryl-and vinylboronic acid reagents.[1] While most reports deal with disubstituted substrates, the construction of enantioenriched all-carbon quaternary stereocenters is still a synthetic challenge.[2] Recently, a number of interesting reports concerning the copper-catalyzed version provided solutions to this problem. However, the use of the classical alkylzinc reagents requires special conditions, such as reactive substrates, for example, nitroalkenes [3] and doubly activated enones.[4] Less-reactive trisubstituted cyclic enones are only accessible with specialized N-heterocyclic carbene (NHC) ligands [5] or more reactive nucleophiles, such as, trialkylaluminum reagents. In combination with stronger coordinating solvents, their enhanced Lewis acidity has made trialkylaluminum reagents very successful in the ACA.[6] Grignard reagents are also useful owing to their wide scope of reaction, but the enantioselectivities are generally lower than with Al and Zn reagents.[7]Although quaternary centers are ubiquitous motifs in natural and pharmaceutical products, only few reports deal with their formation through the ACA. Most examples are limited to the addition of phenyl and p-anisyl,[5, 7] the aryl group is already present in the substrate [6c, d] or activated substrates [8] are required. To date, no general method has been developed to introduce a wide range of aromatic groups to trisubstituted enones. In our search for a solution to this problem, we turned our attention to aluminum reagents, as they had proven to be very successful in the introduction of alkyl substituents. However, aryl aluminum reagents are not commercially available. Similarly, the commercial availability of aryl zinc reagents is restricted to diphenyl zinc and other routes have been developed to obtain the desired compounds, such as transmetalation of arylboronic acids with diethyl zinc [9] or of aryl lithiums with zinc dichloride.[8b, 10] We therefore envisaged generating aryl alanes in similar ways. First, the phenyl transfer from phenylboronic acid to
