A GENERAL DIASTEREOSELECTIVE SYNTHESIS OF SPIROACETALS RELATED TO THOSE IN IONOPHORES VIA THE REACTION OF LACTONES WITH CERIUM(III) GAMMA-CERIOALKOXIDE - MAD REVERSES THE DIASTEREOSELECTIVITY OF THE ADDITION OF METHYLMETALLICS TO A BETA-KETO ETHER

The following steps constitute a fairly general and stereoselective sy nthesis of spiroacetals. 1. Thiophenol is added to acrylic acid. 2. Th e latter is treated consecutively with butyllithium, CeCl3, and an org anolithium compound. 3. The resulting 3-(phenylthio) ketone is either reduced in the presence of zinc ion to yield mainly one diastereomer o r treated with methyllithium or methylmagnesium chloride in the presen ce or absence of methylaluminum bis(2,6-di-tert-butyl-4-mthylphenoxide ) (MAD, 25) to yield selectively either of two diastereomeric 3-(pheny lthio) alcohols. 4. The alcohol is treated with butyllithium, lithium 4,4'-di-tert-butylbiphenylide (LDBB), and CeCl3, to yield a cerium(III ) gamma-cerioalkoxide, which is added to a lactone, the reaction being quenched with acid. In the addition to the keto ether in the absence of MAD, methyllithium or methylmagnesium chloride give very predominan tly the erythro alcohol, presumably via Cram's chelate model, while in the presence of excess MAD, the three product is very predominant, po ssibly because each oxygen atom is complexed with the bulky aluminum r eagent. The methodology is demonstrated by the preparation of diastere omeric spiroacetals related to those found in a number of natural iono phores by using as the reaction partner of the carboxylate salt, alpha -lithio tetrahydrofuran or tetrahydropyran, readily generated by reduc tive lithiation of the corresponding alpha-(phenylthio) heterocycle wi th LDBB, and by employing methylmetallics rather than reducing agents for the reaction with the ketone.