Abstract
Deracemisation of racemic compounds is still the most important strategy to produce optically pure compounds despite many recent advances in asymmetric synthesis. Especially deracemisation approaches that give rise to single enantiomers are preferred, which can be achieved either by invoking organocatalysts, metal complexes or enzymes - leading to dynamic kinetic resolution - or by applying other deracemisation techniques based on stereoinversion or enantioconvergence. In this tutorial review, we will provide an overview of new, recently developed approaches that lead to the important goal of creating organic compounds of single chirality.
Highlights
The synthesis of enantiomerically pure compounds remains a challenge in modern organic chemistry due to the importance of chirality in biological processes
The most recent report of Birman’s group describes the Dynamic kinetic resolution (DKR) of a-arylthio- and a-alkylthioalkanoic acids.[6]. This latest example was inspired by the serendipitous finding that a-arylthioesters are readily racemised by the previously mentioned amidine-based catalysts, thereby opening up the possibility of DKR
After screening of acyl donors with varying chain length (R = Me to octyl), 4-chlorophenyl valerate (R = Bu) was found to be the most appropriate in DKR of phenylethanol. Employing this acyl donor in DKR of 1-phenylethanols with various substitution patterns in the phenyl ring resulted in yields and ee’s up to 99% in almost all cases
Summary
The synthesis of enantiomerically pure compounds remains a challenge in modern organic chemistry due to the importance of chirality in biological processes. The best results in terms of conversion and ee were obtained using (S)-BTM 3 as the catalyst (Scheme 2) Under these slightly acidic conditions, the azlactone 1 racemizes via the corresponding enol, while the chiral acyl transfer catalyst causes the sterically congested alcohol nucleophile (4) to react faster with the (S)- than with the (R)-enantiomer. The most recent report of Birman’s group describes the DKR of a-arylthio- and a-alkylthioalkanoic acids.[6] This latest example was inspired by the serendipitous finding that a-arylthioesters are readily racemised by the previously mentioned amidine-based catalysts, thereby opening up the possibility of DKR In this process the alkanoic acid 10 was first reacted with an activator resulting in the formation of the corresponding anhydride in the presence of base (iPr2NEt) (Scheme 4). Substrate 16 was transformed into the desired lactone in high yield (86%), good d.r. (6 : 1) and excellent ee (98%)
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