Nucleophilic additions to and reductiosn of 5-formyl-and 5-acyl-2-isoxazolines (4,5-dihydeoisoxazoles): a stereoselective route to β,γ-dihydroxy ketones

Abstract

Reductions of readily available 5-acyl-2-isoxazolines with L-Selectride follow the Felkin–Anh model and produce syn-5-hydrodyallkyl-2-isoxazolines with excellent (>95 : 5) selectives. Swern oxidation of 5-hydroxymethyl-2-isoxazolines, followed by direct addition of a Grignard reagent to the intermediate 5-formyl-2-isoxazolines, also follows the Felkin–Anh model and produces anti-5 hydroxyalkyl-2-2 isoxazolines with modest (80 : 20) to excellent (>95.5) selevtivity. In contrast, additions of Grignard regents to 5-acyl-2-isoxazolines follow the chelation model, and give syn or anti products (depending on choice of acyl substiuent and Grignard reagent) with good (90 : 10) to excellent selectivity. These selectivities are almost always far superior to those that can be obtained by direct nitrile oxide cycloaddition to a chiral allylic alcohol ro ether. The resulting products are readily reduced to syn-or anti-β,γ-dihydroxy ketones. A speculative model to explain this surprising reversal in selectivity between formly and acyl isoxazolines is proposed.