( R)- and ( S)-3-Hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as chiral auxiliaries in Diels–Alder reactions

Abstract

A study of the Diels–Alder reactions of the esters derived from acrylic, methacrylic, trans-crotonic and trans-cinnamic acid and the chiral auxiliaries ( R)- and/or ( S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone ( 4, 17, 25 and 26, respectively) with different dienes [cyclopentadiene 5, isoprene 8, 11,12-dimethylene-9,10-dihydro-9,10-ethanoanthracene 9 and anthracene 10], catalyzed by titanium tetrachloride, is described. Cyclopentadiene gave adducts with esters ( R)- or ( S)- 4 and ( R)- 25 with high endo- and facial-diastereoselectivities. Diene 5 reacted with (±)- 17 without endo-diastereoselectivity and failed to give a cycloadduct with (±)- 26. Isoprene reacted only with ester ( S)- 4 with high facial-diastereoselectivity. The reaction of 9 with ( R)- 4 failed, because the diene was not stable under the acid reaction conditions. Adducts derived from 10 and esters ( S)- 4 and ( R)- 17 could be obtained with high facial-diastereoselectivity. LiOH-hydrolysis of the adducts derived from esters ( R)- or ( S)- 4 and ( R)- 25 gave the corresponding enantiopure acids, the chiral auxiliaries being completely recovered unchanged. However, hydrolysis of the adduct derived from 10 and ( R)- 17, required more drastic basic conditions which partially epimerized the chiral auxiliary. X-Ray diffraction analysis of the adducts derived from 10 and esters ( S)- 4 and ( R)- 17, let us establish their relative configurations and, taking into account the absolute configuration of the starting chiral auxiliary, their absolute configurations.