STEREOSELECTIVE PROTONATION OF CARBANIONS .5. EFFECTS OF REACTION CONDITIONS ON THE ENANTIOSELECTIVE PROTONATION OF LACTONE ENOLATES

Protonation of the enolates 1Li and 2Li by using standard conditions yields enantioselectivities up to 54 and 50% ee, respectively, depending on the chiral proton source[1]. These values may change dramatically by the following variations (standard ee's in parenthesis): (i) In Et2O/THF (90:10) (S)-2 with 72% ee (44%) is formed with (R)-pantolactone (3) but only 48% ee (39%) with (R,R)-tartaric ester 4 (Figure 1). (ii) Lewis acids may produce rac-2 (SnCl2, MgBr2) or definitely increase the enantioselectivity: With lactone 3: 46% ee (44%); with esters 4: 48% ee (39%); with bissulfonamide 7: 67% ee (47%) (Table 1,2). (iii) Lithium chloride (2-4 equiv.) in THF yields (S)-1 with 68% ee (47%) and (S)-2 with 77% ee (39%) but only if ester 4 ist employed as chiral proton source (Figure 2). (iv) Chiral Lewis bases create (S)-2 with up to 30% ee on protonation with achiral acids (Table 3, 4). (v) Deuteration of 2Li ranges from 16 to 95% depending on the nature of the base as well as the deuteron source. The degrees of deuteration and enantioselectivity are not correlated. All results demonstrate the complexity of enantioselective protonation of enolates which still needs empirical optimization.