Optically active cyanohydrins are synthetic precursors of R-hydroxy carboxylic acids, R-amino carboxylic acids, β-hydroxy amines, and several other classes of organic compounds of biological importance. Existing methods for the preparation of chiral cyanohydrins include both enzymatic 1,2 and chemical processes. 1,3 Chemically, several efficient methods have been developed. In most of these methods, however, the chiral ligands are rather unstable and cannot be easily recovered. We now describe a new chiral Ti(IV) catalyst with dihydroxy-trans-1,2-diamide 3a as the ligand, which effects the enantioselective addition of trimethylsilyl cyanide to aldehydes.Ligand 3a and its diastereoisomer 3b were prepared from ketopinic acid chloride (1) 4 according to the Scheme 1. On treatment with optically pure (+)-or (-)-trans-1,2-diaminocyclohexane in dichloromethane in the presence of triethylamine, ketopinic acid chloride was converted to the trans-diketoamide 2a or 2b, respectively. Diketoamide 2a and 2b could also be obtained in pure form by reacting ketopinic acid chloride with (+)-trans-1,2-diaminocyclohexane in the same fashion as above followed by separation of the resulting diastereomeric mixture by column chromatography on silica gel. Subsequent reduction of 2a and 2b using L-selectride in tetrahydrofuran at -78 °C for 1 h and then at room temperature for 2 h gave 3a and 3b, respectively with the hydroxy group at the exo position. 5 The absolute stereochemistry of ligand 3a was further determined by X-ray crystallographic analysis. Ligand 3a was found to be an useful chiral ligand for asymmetric induction (eq 1). In conjunction with titanium tetraisopropoxide, ligand 3a was shown to effect the enan-
Highly enantioselective silylcyanation of aliphatic and aromatic aldehydes was achieved by using a 1,2-diphenylethylenediamine linked chiral Ti(IV) complex as the catalyst.
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