The bismuth-mediated two-component hemiacetal/oxa-conjugate addition of δ-trialkylsilyloxy and δ-hydroxy α,β-unsaturated aldehydes and ketones with alkyl aldehydes provides the syn-1,3-dioxanes in a highly efficient and stereoselective manner. The key advantages of this protocol are its operational simplicity and its ability to directly access electron-withdrawing groups without recourse to oxidation state adjustments.
The concise enantioselective synthesis of the revised C1–C31 fragment of the polyketide amphidinol 3 was accomplished in 16 steps and 12.8% overall yield.
The bismuth-mediated two-component hemiacetal oxa-conjugate addition of γ-hydroxy-α,β-unsaturated ketones with paraformaldehyde affords anti-4,5-disubstituted-1,3-dioxolanes in an efficient and stereoselective manner. The reaction provides a practical, inexpensive and atom-economical approach to these types of heterocycles, which represent useful intermediates for target-directed synthesis and precursors to syn-1,2-diols.
The temporary silicon-tethered ring-closing metathesis of chiral non-racemic allylic and homoallylic alcohols affords unsymmetrical Z-configured trisubstituted olefins that readily undergo stereoselective hydroboration and dihydroxylation to provide a novel approach to masked polypropionate and polyol fragments present in an array of biologically important natural products. For example, this strategy provides a convenient method for the construction of polyol fragments relevant to the secondary metabolites amphidinol 3 and lophodiol A, which have antifungal and cytotoxic activity, respectively.The stereoselective construction of structurally diverse polyketides is of particular interest due to their ubiquity in biologically important natural products ( Figure 1). 1 In this context, the development of new methodology that provides complementary routes for the preparation of these challenging motifs is of great synthetic importance since it can lead to the development of new strategies that expedite the synthesis of these types of agents. 2 In a program directed toward the exploration of new synthetic methodologies based on the temporary silicon-tethered ring-closing metathesis (TST-RCM), we have developed a novel approach for the synthesis of protected C 2 -symmetrical 1,4-diols using chiral non-racemic allylic alcohols (Scheme 1A). 3,4 The inherent advantage of this approach is the ability to couple a variety of allylic alcohols and functionalize the newly formed geometrically defined Z-olefin to enable the rapid construction of molecular complexity. 4-6 In a related study, we developed a new strategy for controlling long-range asymmetric induction using a bis-alkoxysilane that contains a prochiral bis-allylic alcohol (Scheme 1B). 5 In an effort to further extend this methodology, we envisioned that the construction of unsymmetrical medium-ring Z-silaketals would provide an opportunity to stereoselectively functionalize the Z-configured trisubstituted olefin using the propensity for the eight-membered silaketal to adopt a defined conformation and thereby enforce high facial selectivity in the addition. 5-9 Herein, we now describe the highly Scheme 1 Temporary silicon-tethered ring-closing metathesis approach to Z-configured silaketals: a new strategy for the stereoselective construction of polypropionates and polyols O Si O R R O Si O R R O Si O R R OH HO + cat.
Diastereoselective Construction of syn-1,3-Dioxanes via a Bismuth-Mediated Two-Component Hemiacetal/Oxa-Conjugate Addition Reaction. -δ-Hydroxy and δ-silyloxy α,β-unsaturated ketones and aldehydes undergo the title reaction with aliphatic aldehydes to give the desired dioxanes in almost diastereomerically pure form. -(EVANS*, P. A.; GRISIN, A.; LAWLER, M. J.; J. Am. Chem. Soc. 134 (2012) 6, 2856-2859, http://dx.
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