Kinetic resolution
AssigneeThe Provost, Fellows, Foundation Scholars, and the Other Members of Board, of the College of the Holy and Undivided Trinity of Queen Elizabeth Near Dublin
InventorsStephen Joseph Connon, Aldo Peschiulli, Barbara Procuranti
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Abstract
While methodologies for the Kinetic Resolution of alcohols are well established, no analogous direct methods exist for the highly selective, direct catalytic Kinetic Resolution of thiols (i.e., R—SH). The present invention relates to a method for resolving stereoisomeric mixtures of thiols. In particular, the present invention relates to purely organocatalytic mediated resolution of enantiomeric mixtures of thiols without the need for enzymes. Also disclosed are some novel catalysts. Such catalysts may comprise a cinchona alkaloid-derived moiety.
Claims19
A method of resolving a mixture of stereoisomers of a thiol comprising the step of preferentially acylating one thiol stereoisomer in the presence of a bifunctional organocatalyst;
- wherein the bifunctional organocatalyst is selected from the group consisting of:
- wherein Z is a C1 to C5 carbon chain optionally comprising at least one C—C unsaturated bond, and optionally substituted one or more times with at least one of a halogen, cyano, CF3, NO2, C1-C5 ketone, C1-C5 ester, C1-C10 amide, C1-C5 sulfone, C1-C5 sulfoxide and combinations thereof;
- and
- M is H, OH, or OMe.
A process for the preparation of enantioenriched 3-(aminomethyl)-5-methylhexanoic acid comprising the steps of:
- i) preferentially acylating one thiol enantiomer of an enantiomeric mixture of the thiol with 3-isobutylglutaric anhydride in the presence of a bifunctional organocatalyst;
- wherein the bifunctional organocatalyst is selected from the group consisting of:
- wherein Z is a C1 to C5 carbon chain optionally comprising at least one C—C unsaturated bond, and optionally substituted one or more times with at least one of a halogen, cyano, CF3, NO2, C1-C5 ketone, C1-C5 ester, C1-C10 amide, C1-C5 sulfone, C1-C5 sulfoxide and combinations thereof;
- and
- M is H, OH, or OMe;
- and
- ii) converting the thioester functional group into an amine.
A molecule having the general structure:
- wherein Z is a C1 to C5 carbon chain optionally comprising at least one C—C unsaturated bond, and optionally substituted one or more times with at least one of a halogen, cyano, CF3, NO2, C1-C5 ketone, C1-C5 ester, C1-C10 amide, C1-C5 sulfone, C1-C5 sulfoxide and combinations thereof;
- and
- M is H, OH, or OMe.
Dependencies are inferred from the claim text.