ON THE SCOPE OF ASYMMETRIC NITRILE OXIDE CYCLOADDITIONS WITH OPPOLZERS CHIRAL SULTAM - TOTAL SYNTHESES OF (+)-HEPIALONE, (-)-(1R,3R,5S)-1,3-DIMETHYL-2,9-DIOXABICYCLO[3.3.1]NONANE, AND (-)-(1S)-7,7-DIMETHYL-6,8-DIOXABICYCLO[3.2.1]OCTANE

Cycloadditions of nitrile oxides with acryloyl derivatives of Oppolzer’s chiral sultam produce stereoisomeric Δ2-isoxazolines in ratios of about 90/10 at 25 °C. The major diastereomers can be isolated in pure form in 70-88% yield. Syntheses of the three title natural products are used to illustrate that optically pure isoxazolines can be transformed into a wide variety of functional groups including β,γ-dihydroxy ketones, alcohols, 1,2- and 1,3-diols, 1,3,4-triols, 1,3-amino alcohols, and 1,3,4-amino diols. It is suggested that this cycloadditive strategy complements existing asymmetric aldol routes to such functionality. A novel radical ring opening was discovered when it was found racemic 5-methyl-A2-isoxazolines are formed upon reduction of optically pure 5-(iodomethyl)-Δ2-isoxazolines with tributyltin hydride at low concentration. The scope of the asymmetric cycloaddition was studied by using methacryloyl sultam 33 and crotonoyl sultam 36. The methacryloyl sultam exhibits very low levels of asymmetric induction, and is much less reactive than a methacrylate ester model. An X-ray crystal structure of 33 suggests a reason for this behavior: the methacryloyl group deviates significantly from planarity. The crotonoyl sultam 36 provides good levels of diastereoselectivity (90/10) in the nitrile oxide cycloaddition, but regioselectivity is lacking. © 1990, American Chemical Society. All rights reserved.