The aldol and related carbonyl condensation reactions have long been among the cornerstones of organic synthesis. The plan proposes a fundamentally different and general alternative for the formation of traditional carbonyl condensation constructs. The strategy involves nitrile-oxide olefin cycloaddition followed by reduction and hydrolysis of the resultant substituted isoxazoline. Preliminary results have already demonstrated the Beta-hydroxy-ketones can be prepared via this """"""""non-condensative"""""""" route with complete stereo-and regiocontrol. Methods are proposed to extend this reaction to form Beta-hydroxy-esters, acids, and aldehydes, as well as various Beta-dicarbonyls. The sequence is generally complimentary to carbonyl condensation, occurring under very mild conditions. Methods are proposed to control stereo-and regiochemistry of nitrule-oxide cycloadditions via Lewis Acid catalysis of novel classes of nitrile oxides. A fundamentally new approach to generation of nitrile oxides from nitrile oxides is proposed. This may make available several unknown classes of nitrile oxides as well as shorten the preparation of common types. The usefulness of the new methodology is illustrated by proposed syntheses of several important classes of natural products including prostanoids, iridiods, macrolides, and anthracyclines among others. Thus it is proposed that this method may be the first general non-condensative method to traditional carbonyl condensation adducts. This generally complimentary route has certain advantages which may recommend it as a viable alternative to the widely used aldol type reactions.
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