Chiral auxiliaries as docking/protecting groups in biohydroxylation: The hydroxylation of enantiopure spirooxazolidines derived from cyclopentanone using Beauveria bassiana ATCC 7159

The aim of this work was to explore the scope and Limitations of chiral doc king/protecting groups as chiral auxiliaries in the biohydroxylation of una ctivated methylene groups. As a model compound, cyclopentanone 1 was reacte d with a range of enantiomerically pure amino alcohols 2a-n as well as 7a a nd b, varying substituents R-1 and R-2. The resulting chiral spirooxazolidi nes 3a-n as well as 8a and b were exposed to the fungus Beauveria bassiana ATCC 7159 and the resultant hydroxylated products were characterised. Intro ducing chirality into the substrate before the fermentation was found to ha ve a major effect on the course of the biohydroxylation relative to the ach iral analogue 3a (Table 1, entry 1). The nature of R-1/R-2 influenced both the product yield and the optical purity of the products (e.g. Table 1, ent ry 2). In addition, the absolute configuration of the final product 6 could be dictated solely by the nature of the docking/protecting group used (com pare entry 8 with entry 9). Concerning the chain length of R-1/R-2, it was found that hydroxylation only took place in the cyclopentane ring when the heterocyclic ring was substituted with a methyl, ethyl or isopropyl (entrie s 2-5, 8, 9, 15, and 16). With increasing chain length, where R1/R2 are pro pyl, isobutyl or sec-butyl groups, a mixture of products was obtained in wh ich the hydroxyl group was either on the cyclopentane ring or on the sidech ain (entries 10-14).