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 R 1 and R 2 . 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 R 1 /R 2 influenced both the product yield and

Chiral Auxiliaries as Docking/Protecting Groups in Biohydroxylation:(S)‐Specific Hydroxylation of Enantiopure tert‐Butyl‐Substituted Spirooxazolidines Derived From Cyclopentanone

“…Subsequent reaction with cyclopentanone afforded the desired, enantiopure substrates 7 and 8 , respectively (Scheme ). In contrast to previous observations, these compounds were obtained in only modest yields under standard, unoptimized conditions5,8 (22 % and 17 %, respectively).…”

“…Satisfyingly, although ketone 4 was found to be ( R )‐configured (19 % ee ), ketone 11 was found to be ( S )‐configured and with a high ee (89 %). It should be mentioned at this point that, based on published experiments5 with product 3 , this ee value should increase after simple recrystallisation of compound 9 . This result nicely complements those obtained from the ( R )‐methyl d/p used in previous studies (Scheme ) where product 3 could be obtained in 90 % de in a single biohydroxylation step.…”

“…Spirooxazolidine Derivative 8: Employing the standard procedure for preparing spirooxazolidine derivatives,5 compound 8 was prepared in 17 % yield as a pale‐yellow, crystalline solid. M.p.…”

“…Biohydroxylation Product 10: Employing published methods,5 treatment of compound 8 (759.6 mg) with Beauveria bassiana ATCC 7159 gave the title compound (160.6 mg), together with unreacted starting material (65.8 mg), as a white solid (22 % yield, taking into account unreacted starting material). M.p.…”

“…Chiral d/p groups have also been investigated5,6 and employed for the hydroxylation of ketones. In this manner, the stereoselective functionalisation of these compounds was achieved.…”