The asymmetric aldol reaction of an enolate or enolate equivalent with an imine is a reaction of established synthetic importance for the synthesis of chiral amines in general and bamino esters in particular. [1] The development of chiral catalysts for this reaction has proven to be a difficult task and had eluded all attempts until recently when Kobayashi and co-workers examined imines derived from o-aminophenol. [2±4] Their method involves the catalysis of the reactions of these imines and ketene acetals with a catalyst generated from zirconium(iv) tert-butoxide and two equivalents of (R)-6,6'-dibromoBINOL (BINOL 1,1'-binaphth-2-ol). Our interest in the synthesis of chiral amines led us to investigate the use of VAPOL-derived catalysts A comparison of catalysts prepared from BINOL, 6,6'-dibromoBINOL and VAPOL ligands on the asymmetric induction in the reaction of the phenyl-substituted imine 1 and acetal 2 is summarized in [2] The VAPOL catalyst could be prepared in either methylene chloride or toluene, but for solubility reasons, the BINOL catalysts were prepared in methylene chloride. The VAPOL and Br 2 BINOL catalysts were superior to the BINOL catalyst at À 45 8C. The asymmetric induction dropped for the Br 2 BINOL catalyst when the temperature was raised from À 45 8C to room temperature, but curiously, the asymmetric induction for the VAPOL catalyst was essentially unchanged over this same temperature range. Only a small drop-off is noted (85 % ee) when the temperature is raised to 41 8C and the substrate-to-catalyst ratio is raised to 200:1 (entry 5). Both the R enantiomers of BINOL and Br 2 BINOL ligands give the R enantiomer of the product 3, whereas with the VAPOL ligand, it is the S enantiomer that gives the R product. This reversal is not unexpected given the structures of the ligands where the zirconium is in the minor groove of the BINOL ligands and in the major groove of the VAPOL ligand. [2g] It is clear from the examination of space-filling CPK models that it is possible to bind two VAPOL ligands to one zirconium atom but only with a facial arrangement of the four oxygen atoms as is illustratred by structure 6 in Scheme 1. This is supported by 1 H NMR experiments on a catalyst generated from zirconium tetraisopropoxide and VAPOL in the presence of two equivalents of N-methyl imidiazole. A clean spectrum is only observed with two equivalents of VAPOL relative to zirconium and the spectrum is consistent with a single C 2 -symmetrical species were performed by using the TEXSAN [13] crystallographic software package. Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-153832. Copies of the data can be obtained free of charge on application to CCDC
