Divergent Kinetic Control of Classical versus Ozonolytic Lactonization: Mechanism-Based Diastereoselection

Citations Over Time

Abstract

A strategy has been developed in which mechanistically distinct lactonization reactions are used to prepare diastereomeric delta-lactones relevant to the C1-C9 fragment of (+)-peloruside A. Depending upon which of two reaction types is used, the central (C5) hydroxyl group can be directed to differentiate the C1 versus C9 termini of pseudosymmetric substrates to provide diastereomeric lactones. Thus, the 5-hydroxy-1,9-diester substrate 1 (an azelaic ester) cyclizes under classical (acid- or base-catalyzed) lactonization conditions to give a predominance of one diastereomer, whereas the 5-hydroxy-1,10-diene congener 2 provides the opposite sense of diastereoselectivity when subjected to ozonolytic lactonization (O3, MeOH, NaOH, at -78 degrees C). Thus, this under-utilized oxidative transformation is mechanistically orthogonal to the classical reaction.

Related Papers

• → Diastereomer-Differentiating Photochemistry of β-Arylbutyrophenones: Yang Cyclization versus Type II Elimination(2005)25 cited
• → NMR INVESTIGATIONS ON DIASTEREOMERIC MIXTURES OF BIS(DIALKOXYTHIOPHOSPHORYL) SULFANES AND -POLYSULFANES CONTAININGsec. BUTOXY GROUPS. ASSIGNMENT OF31P,13C AND1H NMR SIGNALS IN A MIXTURE OF SEVEN DIASTEREOMERS USING SHIFT-CORRELATED 2D NMR SPECTRA(1991)12 cited
• → Compound Separation by Cyclic, Selective Dissolution. Isolation of Diastereomeric, 1β-Methylcarbapenem Key Intermediates(1993)3 cited
• → Synthesis of Tricholomic Acid. VIII. Synthesis of Diastereoisomers of Isotricholomic Acid from β-Hydroxyglutamic Acid γ-Esters(1969)2 cited
• → Synthesis of threo-4,5-dihydroxy diastereomers of sphinganine(1975)