The Stereochemistry of Nucleophilic Addition. II. The Reformatsky Reaction of Methyl (+)-α-Bromopropionate, 2-Phenylpropanal, and 3-Phenyl-2-butanone

Abstract

Abstract The Reformatsky reaction of methyl (+)-α-bromopropionate with benzaldehyde was carried out in order to study the reaction mechanism, and two epimeric methyl 3-hydroxy-2-methyl-3-phenylpropionates (IIa and IIb) were obtained in a 59 : 41 ratio. From a comparison of the optical activity of IIb with that of pure (−)-IIb, it was estimated that lib consists only seven percent of an optically-active compound; this results supports the hypothesis of the enolate anion mechanism. Subsequently, the stereochemistry of this reaction with 2-phenyl-propanal (IV) and 3-phenyl-2-butanone (VIII) was studied. The condensation of IV with methyl bromo-acetate gave a mixture of the epimeric methyl 3-hydroxy-4-phenylvalerates (Va and Vb), which were separated in a 26 : 74 ratio by means of column chromatography on silica gel. Similarly, VIII was also condensed with methyl bromoacetate to give the epimeric methyl 3-hydroxy-3-methyl-4-phenylvalerates (IXa and IXb) in a 31 : 69 ratio. The configurations of these esters were assigned by correlation with the products of the Grignard reaction, the stereochemistry of which is well known. From the present study, it is clear that the Reformatsky and the Grignard reactions of the carbonyl compound having an asymmetric α-carbon atom proceed in a similar fashion; that is, the entering group predominantly approaches the carbonyl group from the least-hindered side. Therefore, Gram’s rule of asymmetric induction can be applied in the stereochemistry of the Reformatsky reaction.