A USEFUL MODIFICATION OF THE EVANS AUXILIARY - 4-ISOPROPYL-5,5-DIPHENYLOXAZOLIDIN-2-ONE

The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250 degrees, a low solubility in most organic so lvents, and a C=O group which is sterically protected from nucleophili c attack. Thus; the soluble N-acyl-oxazolidinones (7-16) can be prepar ed from 1 with BuLi at temperatures around 0 degrees instead of - 78 d egrees (Scheme 3): their Li enolates can be generated with BuLi, rathe r than with LDA, and deacylation in the final step of the procedure ca n be achieved with NaOH at ambient temperatures (Scheme 12),with facil e recovery of the precipitating auxiliary 1 (filtering, washing, and d rying). The following reactions of N-acyl-oxazolidinones from 1 have b een investigated: alkylations (Scheme 4), aminomethylations and hydrox ymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael a dditions (Schemes 9 and 10), and a (4 + 2) cycloaddition (Scheme II). The well-known features of reactions following the Evans methodology ( yield, diastereoselectivity, dependence on conditions, counter ions, a dditives etc.) prevail in these transformations. Most products, howeve r, have higher melting points and a much more pronounced crystallizati on tendency than those derived from conventional oxazolidinones, and c an thus be purified by recrystallization, avoiding chromatography (Tab le 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensate d by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TICl4 com plex of an oxazolidinone are described and discussed in view of the di astereoselective-reaction mechanisms.