Understanding the Stereoselection Induced by Chiral AnthraceneTemplates in Diels—Alder Cycloaddition: A DFT Study

摘要

Recyclable chiral anthracene templates have emerged as an effective and well-designed approach in preparingcomplex biologically active molecules such as butenolides, α,β-unsaturated lactams, and related compoundsin their enantiomerically pure forms. Highly diastereoselective initial cycloaddition serves as the key elementof the total process, as it determines the final stereochemistry of the product. The diastereoselectivity of chiralanthracene templates is explored by using density functional theory (DFT) methods, and the reliability andapplicability of the previously proposed models, mostly based on steric arguments, are tested by mechanisticmeans. The diastereomers A and B are identified according to the stereochemistry around the formed stereocenteron the dienophile attached to C9, as being R or S, respectively. The reactions of (R)-9-(1-methoxyethyl)an-thracene and (S)-9-(1-methoxy-2,2,2-trifluoroethyl)anthracene with maleic anhydride both give exclusivelydiastereomer A via a similar transition state in which the CH3/CF3 group is antiperiplanar to the approachingdienophile. The major product of the reaction between (R)-9-(1-phenylethyl)aminoanthracene and maleicanhydride is diastereomer B. The geometry around nitrogen is close to planar in the transition state (10-25°out of plane), and the nitrogen lone pair is antiperiplanar to the incoming dienophile. Both of the lowestenergy diastereomeric transition states giving A and B benefit from the favorable interaction between thecarbonyl oxygen and the amine hydrogen; this interaction does not play a substantial role in the selectivity ofthe reaction as previously proposed. The diastereomeric transition states leading to A and B for the reactionbetween (R)-9-acyloxyanthracene and maleic anhydride have very similar interactions around the reactioncenter, leading to a very small energy difference between the diastereomeric transition states. The productdistribution ratios for all templates calculated from Boltzmann distributions agree very well with the experimentalresults.