Kinetic resolution

摘要

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.

主权项

1. 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 X can be O or S; Z can be 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 halogen, cyano, CF3, NO2, C1-C5 ketone, C1-C5 ester, C1-C10 amide, C1-C5 sulfone, C1-C5 sulfoxide and combinations thereof; M can be H, OH, or OMe; B can be C1-C15 alkyl, C3-C15 cycloalkyl, C5-C15 aryl, C5-C15 heteroaryl or combinations thereof, optionally substituted one or more times with at least one of halogen, cyano, CF3, NO2, C1-C5 ketone, C1-C5 ester, C1-C10 amide, C1-C5 sulfone, C1-C5 sulfoxide, C1-C5 alkyl and combinations thereof; R3 can be C1-C15 alkyl, C5-C15 aryl ring, or C5-C15 heteroaryl ring which may be optionally substituted one or more times with at least one of halogen, cyano, CF3, NO2, C1-C5 ketone, C1-C5 ester, C1-C10 amide, C1-C5 sulfone, C1-C5 sulfoxide, C1-C5 alkyl and combinations thereof.