Chiral Auxiliaries as Docking/Protecting Groups in Biohydroxylation: The Hydroxylation of Enantiopure Spirooxazolidines Derived from Cyclopentanone UsingBeauveria bassiana ATCC 7159

Abstract

The aim of this work was to explore the scope and limitations of chiral docking/protecting groups as chiral auxiliaries in the biohydroxylation of unactivated methylene groups. As a model compound, cyclopentanone 1 was reacted with a range of enantiomerically pure amino alcohols 2a−n as well as 7a and b, varying substituents R1 and R2. The resulting chiral spirooxazolidines 3a−n as well as 8a and b were exposed to the fungus Beauveria bassiana ATCC 7159 and the resultant hydroxylated products were characterised. Introducing chirality into the substrate before the fermentation was found to have a major effect on the course of the biohydroxylation relative to the achiral analogue 3a (Table 1, entry 1). The nature of R1/R2 influenced both the product yield and the optical purity of the products (e.g. Table 1, entry 2). In addition, the absolute configuration of the final product 6 could be dictated solely by the nature of the docking/protecting group used (compare entry 8 with entry 9). Concerning the chain length of R1/R2, it was found that hydroxylation only took place in the cyclopentane ring when the heterocyclic ring was substituted with a methyl, ethyl or isopropyl (entries 2−5, 8, 9, 15, and 16). With increasing chain length, where R1/R2 are propyl, isobutyl or sec-butyl groups, a mixture of products was obtained in which the hydroxyl group was either on the cyclopentane ring or on the side-chain (entries 10−14).