Diastereofacial Selection in Nitrile Oxide Cycloaddition Reactions. The Anti-Directing Effect of an Allylic Oxygen and Some New Results on the Ring Metalation of Isoxazolines. A Synthesis of (±)-Blastmycinone.

Abstract

The extent of diastereoselectivity associated with the reactions of nitrile oxides with alkenes bearing an allylic oxygen substituent has been studied. Reasonable levels of such diastereoselectivity have been found when the tert-butyldimethylsilyl ether derivative of 3-buten-2-ol (5) or (+)-(S)-isopropylidene-3-butene-1,2-diol (1) are employed as dipolarophiles. The stereochemical course of these cycloaddition reactions has been proven rigorously through the transformation of the adducts to known γ-lactones. The stereochemistry associated with the metalation/alkylation of 5-alkoxymethyl-substituted isoxazolines has also been probed in order to further expand the use of these heterocycles as aldol equivalents in natural products total synthesis. A synthesis of (±)-blastmycinone (34) is reported which combines the two foregoing aspects of stereocontrol. The levels of regio- and stereoselectivity found in the cycloaddition reactions of the cis- and trans-disubstituted alkenes 35 and 39 prepared from isopropylidene-D-glyceraldehyde are also discussed. A single example of the reaction of a chiral alkene with a chiral nitrile oxide is presented.