Asymmetric allylic substitution catalyzed by C1-symmetrical complexes of molybdenum:: Structural requirements of the ligand and the stereochemical course of the reaction

Application of new chiral ligands (R)-(-)-12a and (S)-(+)-12c (VALDY), derived from amino acids, to the title reaction, involving cinnamyl (linear) and isocinnamyl (branched) type substrates (4 and 5 -> 6), led to excellent regio- and enantioselectivities (> 30:1, <= 98% ee), showing that ligands with a single chiral center are capable of high asymmetric induction. The structural requirements of the ligand and the mechanism are discussed. The application of single enantiomers of deuterium-labeled substrates (both linear 38c and branched 37c) and analysis of the products (41-43) by H-2{H-1} NMR spectroscopy in a chiral liquid crystal matrix allowed the stereochemical pathways of the reaction to be distinguished. With ligand (S)-(+)-12c, the matched enantiomer of branched substrate was found to be (S)-5, which was converted into (R)-6 with very high regio- and stereoselectivity via a process that involves net retention of stereochemistry. The mismatched enantiomer of the branched substrate was found to be (R)-5, which was also converted into (R)-6, that is, with apparent net inversion, but at a lower rate and with lower overall enantioselectivity. This latter feature, which may be termed a "memory effect", reduced the global enantioselectivity in the reaction of the racemic substrate (+/-)-5. The stereochemical pathway of the mismatched manifold has been shown also to be one of net retention, the apparent inversion occurring through equilibration via an Mo-allyl intermediate prior to nucleophilic attack. Incomplete equilibration leads to the memory effect and thus to lower enantioselectivity. Analysis of the mismatched manifold over the course of the reaction revealed that the memory effect is progressively attenuated with the nascent global selectivity increasing substantially as the reaction proceeds. The origin of this effect is suggested to be the depletion of CO sources in the reaction mixture, which attenuates turnover rate and thus facilitates greater equilibrium. The linear substrate was also converted into the branched product with net syn stereochemistry, as shown by isotopic labeling. An analogous process operates in the generation of small quantities of linear product from branched substrate.