CHELATION CONTROL IN METAL-ASSISTED ALDOL ADDITION-REACTIONS OF ALPHA-HALOGENATED IMIDE ENOLATES LEADING TO PREDOMINANTLY ANTI-STEREOSELECTIVITY - AN EXAMPLE OF A STEREOCONTROLLED DARZENS REACTION

The aldol reaction of enantiopure N-(haloacetyl)-2-oxazolidinone enolates with aromatic aldehydes was studied for conditions that would induce the reaction to yield predominantly anti adducts. It was found herein that the inherent steric and stereoelectronic properties of the aldehyde (R), as well as its chelative ability with the enolate countercation, are crucial in determining which of its enantiotopic faces reacts. Certain metallic enolates (Sn,IV Zn, and Li) are postulated to react through a three-point coordination transition state to yield mainly anti adducts, while others (Sn,II B, Ti) are shown to react via noncoordinated transition states to yield either syn or anti adducts. X-ray crystallography was instrumental in fully defining the absolute stereochemistry of each product, providing insight into the mechanisms of stereocontrol. The major anti producing pathway for reaction of aromatic aldehydes is postulated to proceed via boatlike or a high-energy ''unfavored chair'' transition state (TS). Finally, using our protocol of varying either the enolate countercation or the substitution pattern on the aromatic aldehyde, we demonstrate how one may synthesize three of the four possible stereoisomers available from this aldol-type reaction, the syn Li isomers 7 being the only inaccessible isomer as a major product in this alpha-halo-2-oxazolidinone system. The anti halohydrins were converted stereospecifically to the trans epoxy esters or epoxy amides in high enantiomeric purity.