Acyclic Stereoselection. 7. Stereoselective Synthesis of 2-Alkyl-3-hydroxy Carbonyl Compounds by Aldol Condensation

Article abstract of DOI:10.1021/jo01294a030

The stereochemistry of the aldol condensation of preformed lithium enolates of a variety of ethyl ketones and propionic acid derivatives with aldehydes has been investigated.It is found that certain compounds give completely or nearly completely one diastereomeric enolate and that the stereostructure of the resulting aldol is correlated with the stereostructure of the enolate from which is formed.The observed stereochemistry may be understood in terms of an ordered transition state in which both oxygens are oriented in more or less the same direction.It is shown that the observed stereochemistry is kinetically controlled.In many cases, the initial aldol adduct equilibrates to furnish predominantly a threo isomer.The rate of equilibration varies widely, ranging from very fast at -60 deg C with the propiophenone-benzaldehyde adduct to slow at 25 deg C for the ethyl tert-butyl ketone-benzaldehyde adduct.The equilibration behavior of lithium ketolates is compared with that of zinc ketolates, and some differences are noted.A method for achieving erythro-threo equilibration via a chloral hemiacetal is presented.A new reagent is introduced (trimethylsilyloxy ketone 36) which may be used to stereoselectively homologate an aldehyde to an erythro α-methyl-β-hydroxy acid.As an application of the use of stereoselective aldol condensations in synthesis, (+/-)-ephedrine (48) has been synthesized from benzaldehyde in 71 percent overall yield.