Synthesis, characterisation and application of enantiomeric isotopomers of Evans’ oxazolidinones

Parallel kinetic resolution of active esters using a quasi-enantiomeric combination of (R)-4-phenyl-oxazolidin-2-one and (S)-4,5,5-triphenyl-oxazolidin-2-one

“…Interestingly, the levels of mutual recognition between the 4,5,5-triphenyl-oxazolidin-2-one (R)-6 and the corresponding (S)-enantiomer of active ester 3 (and its mirror image combination) were noticeably lower than that of its parent (mutual kinetic) resolution involving 4-phenyl-oxazolidin-2-one 1 (78% de for rac-6 vs 94% de for rac-1). 6,12 We next focused our attention on the mutual kinetic resolution of a series of structurally related active esters rac-8, rac-10, rac-12, rac-14 and rac-16 (derived from the DCC coupling of pentafluorophenol with the corresponding carboxylic acids) 12 using 4,5,5-triphenyl-oxazolidin-2-one rac-6 as our mutual resolving component under standard conditions (Scheme 3: entries 2-6). Deprotonation of 4,5,5-triphenyl-oxazolidin-2-one rac-6 using nBuLi in THF at À78°C, followed by the addition of active esters rac-8, rac-10, rac-12, rac-14 and rac-16 in THF, gave after 2 h the corresponding oxazolidin-2-one adducts rac-syn-and rac-anti-9, 11, 13, 15 and 17 in 18-83% yields with 56-94% diastereoisomeric excesses (Scheme 3: entries 2-6).…”

“…The active esters, pentafluorophenyl 2-phenylpropionate rac-3, pentafluorophenyl 2-phenylbutanoate rac-8, pentafluorophenyl 2-(4-methylphenyl)propionate rac-12 and pentafluorophenyl 2-(4-isobutylphenyl)propionate rac-16, have been reported elsewhere. 12 …”

Parallel kinetic resolution of D‐labelled 2‐aryl‐propionic and butanoic acids using quasi‐enantiomeric combinations of oxazolidin‐2‐ones

“…Ref. [22][23][24] From this study, it was apparent that the (R)-enantiomer of oxazolidin-2-one 1 recognized the (S)-enantiomer of the active ester 2 to give oxazolidin-2-one (S,R)-syn-3, and the complementary enantiomeric oxazolidin-2-one (S)-1 recognized the remaining (R)-enantiomer of the active ester 2 to give the enantiomeric adduct (R,S)-syn-3 in an equal and opposite stereochemical sense (Scheme 1). We have also demonstrated that an isotopomeric mixture of quasienantiomeric oxazolidin-2-ones (R)-1 and (S)- [D 2 ]-1 can be used to resolve this active ester (rac)-2 to give an inseparable mixture of labeled and unlabeled oxazolidin-2-ones (S,R)-syn-3 and (R,S)- [D 2 ]-syn-3 in a combined 70% yield with comparable diastereoselection to its unlabeled variant (>94% d.e.)…”

“…(Scheme 1). 22 We now report an extension of this study to the parallel kinetic resolution of a series of deuterium labeled 2-phenyl/aryl propionic and butanoic acids [D 1 ]-4-7 25 using a quasi-enantiomeric combination of isotopomeric and designer oxazolidin-2-ones. For this study, we had to synthe- With these active esters in hand, we next probed their parallel kinetic resolution using an isotopomeric pair of quasi-enantiomeric oxazolidin-2-ones (R) 3 ]-13, respectively in good yields (71%-78%) with high levels of diastereoselectivity (94%-96% d.e.)…”