Lewis acid-mediated ionization

Lewis acid-mediated ionization of acetals also generates electrophilic carbon intermediates that react readily with allylic stannanes.190 Dithioacetals can be activated by the sulfonium salt [(CH3)2SSCH3]+BF4,191... 

A diastereoselective ewrfo-cyclization into an oxidatively generated oxocarbenium ion was a key step in a formal synthesis of leucascandrolide A. Exposing 56 to CAN provided cw-tetrahydropyran 57 in high yield and with excellent stereocontrol (Scheme 3.20). This transformation provides further evidence that oxidative electrophile formation is tolerant of several functional groups and can be applied to complex molecule synthesis. The synthetic sequence also utilized a Lewis acid mediated ionization reaction to form an oxocarbenium ion in the presence of the homobenzylic ether (58, 59), illustrating that two carbocation precursors that ionize through chemically orthogonal conditions can be incorporated into the same structure. 

Oxidative cleavage to the aldehyde followed by reductive amination gave 10, that looks as though it could be poised for intramolecular displacement of the secondary chloride. Nonetheless, Lewis acid mediated ionization followed by cyclization proceeded smoothly, to establish the fourth ring of the natural product. Oxidation state adjustment then completed the synthesis of (-)-Acutumine 3. 

The results of the aldol additions with silyl enol ethers further refined our new model of a Lewis base-catalyzed-Lewis acid-mediated pathway. Use of the N value was clearly predictive of substrate scope, validating our mechanistic scheme and the role of the ionized chloride in the complex. Gratifyingly, the sense of asymmetric induction in all these reactions is the same using the chiral bisphosphoramide (RJi)-S. 

Studies directed toward the selection and application of an exogenous nucleophile for use with this SiCLj/phosphoramide system first focused on the use of allyltri-butylstannane 20 [35]. The stannane is a competent nucleophile in a wide variety of Lewis acid-promoted carbonyl addition reactions [13, 36-38], and in this system it would provide an effective trap for the ionized chloride through formation of tributyltin chloride. Initial experiments using the optimal phosphoramide catalyst (/ )-10 for the SiCL-mediated opening of meso-epoxides gave good yield and a moderate level of enantioselectivity in the addition of the allyl stannane to... 

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