A general diastereoselective synthesis of spiroacetals related to those in ionophores via the reaction of lactones with cerium(III) γ-cerioalkoxide. MAD reverses the diastereoselectivity of the addition of methylmetallics to a β-keto ether

Article abstract of DOI:10.1021/jo00090a036

The following steps constitute a fairly general and stereoselective synthesis of spiroacetals. 1. Thiophenol is added to acrylic acid. 2. The latter is treated consecutively with butyllithium, CeCl₃, and an organolithium compound. 3. The resulting 3-(phenylthio) ketone is either reduced in the presence of zinc ion to yield mainly one diastereomer or treated with methyllithium or methylmagnesium chloride in the presence or absence of methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD, 25) to yield selectively either of two diastereomeric 3-(phenylthio) alcohols. 4. The alcohol is treated with butyllithium, lithium 4,4'-di-tert-butylbiphenylide (LDBB), and CeCl₃, to yield a cerium(III) γ-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 predominantly the erythro alcohol, presumably via Cram's chelate model, while in the presence of excess MAD, the threo product is very predominant, possibly because each oxygen atom is complexed with the bulky aluminum reagent. The methodology is demonstrated by the preparation of diastereomeric spiroacetals related to those found in a number of natural ionophores by using as the reaction partner of the carboxylate salt, α-lithio tetrahydrofuran or tetrahydropyran, readily generated by reductive lithiation of the corresponding α-(phenylthio) heterocycle with LDBB, and by employing methylmetallics rather than reducing agents for the reaction with the ketone.