ABSTRACT
The isolation of single stereoisomers from a racemic (or diastereomeric) mixture by enzymatic or chemical resolution techniques goes in hand with the disposal of 50% (racemate) or more (diastereomeric mixtures) of the "undesired" substrate isomer(s). In order to circumvent this drawback, dynamic systems have been developed for the de-racemization of enantiomers and the de-epimerizations of diastereomers. Key strategies within this area are discussed and are classified according to their underlying kinetics, that is, dynamic kinetic resolution (DKR), dynamic kinetic asymmetric transformations (DYKAT), and hybrids between both of them. Finally, two novel types of DYKAT are defined.
Subject(s)
Thermodynamics , Alcohols/chemical synthesis , Alcohols/chemistry , Aldehydes/chemistry , Amino Acids/chemistry , Catalysis , Enzymes/chemistry , Esters/chemical synthesis , Esters/chemistry , Imines/chemical synthesis , Imines/chemistry , Ketones/chemistry , Kinetics , Molecular Structure , StereoisomerismABSTRACT
A one-pot synthesis of enantiomerically pure syn-1,3-diacetates starting from readily accessible racemic diastereomeric mixtures of 1,3-diols has been realized by combining (i) enzymatic transesterification, (ii) ruthenium-catalyzed epimerization of a secondary alcohol in a diol or diol monoacetate, and (iii) intramolecular acyl migration in a syn-1,3-diol monoacetate. The in situ coupling of these three processes results in an efficient enantioselective synthesis of acyclic syn-1,3-diacetates via combined deracemization-deepimerization and constitutes a dynamic kinetic asymmetric transformation concept. Several differently substituted unsymmetrical, acyclic syn-1,3-diacetates were obtained in yields up to 73% with excellent enantioselectivities (>99%) and good diastereomeric ratios (>90% syn).