LEWIS ACID PROMOTED STEREOSELECTIVE CARBON CARBON BOND FORMATION OF 3-FORMYL-DELTA-2-ISOXAZOLINES

4,5-Disubstituted 3-formyl-DELTA2-isoxazolines undergo the aldol, allylation, and carbonyl ene reactions in the presence of appropriate Lewis acid to give the adducts with an effective 1,3-asymmetric induction. The stereoselectivity of the reaction mainly depends on the nature of the Lewis acid and the relative configuration of the ring. It is remarkable that both diastereomers can be readily prepared stereoselectively. For example, TiCl4 promotes the 1,3-syn-selective aldol reaction over 93/7 of selectivity, while the 1,3-anti adducts are prepared by the reaction catalyzed by BF3.OEt2. This difference in stereoselectivity is to be attributed to the preferable conformation of isoxazoline-Lewis acid complex intermediates, which depends on the nature of Lewis acid. Without the 4-substituent of isoxazolines the selectivity is not observed. The 5-substituent is too far from the formyl carbon to influence the face differentiation of the formyl group. Subsequent treatment of the adducts with LiAlH4 affords 2-amino 1,4-diol derivatives. The protective group of the hydroxyl group on the C(3) side chain is crucial for the stereoselectivity of the reduction. An almost complete diastereoselectivity of the relative configuration at four contiguous stereogenic centers is readily achieved by the reduction of the adducts protected by O-methoxymethyl (O-MOM). Consequently, the present strategy provides a facile method for the preparation of the compounds containing a sequence of several stereocenters.