Highly Diastereoselective Intramolecular Asymmetric Oxidopyrylium-olefin [5 + 2] Cycloaddition and Synthesis of 8-Oxabicyclo[3.2.1]oct-3-enone Containing Ring Systems

Abstract

We have the investigated base mediated asymmetric intramolecular oxidopyrylium-alkene [5 + 2]-cycloaddition reaction which resulted in the synthesis of functionalized tricyclic ring systems containing an 8-oxabicyclo­[3.2.1]­octane core. Intramolecular cycloaddition constructed two new rings, three new stereogenic centers, and provided a tricyclic cycloadduct with high diastereoselectivity and isolated yield. We incorporated an α-chiral center and an alkoxy alkene tether on the substrates and examined the effect of the size of alkyl groups and alkene tether length on diastereoselectivity. The requisite substrates for the oxidopyrylium-alkene cycloaddition reaction were synthesized in a few steps involving alkylation of optically active α-hydroxy amide, furyllithium addition, reduction of resulting ketone, and Achmatowicz reaction followed by acylation of a lactol intermediate. We have proposed stereochemical models for the [5 + 2] cycloaddition reaction via the oxidopyrylium ylide. Interestingly, the alkoxy substituent on the stereocenter and the chain length are responsible for the degree of stereoselectivity of the cycloadduct.

Crystal Engineering of a Chiral Crystalline Sponge That Enables Absolute Structure Determination and Enantiomeric Separation

“…We selected several homochiral aromatic alcohols to evaluate the properties of CMOM-5. In general, such molecules are key precursors to enantiopure pharmaceuticals. − The isomers of 1-phenyl-1-butanol (1P1B), 4-phenyl-2-butanol (4P2B), 1-(4-methoxyphenyl)­ethanol (MPE), and methyl mandelate (MM) are key enantiopure reagents for the total synthesis of chiral pharmaceuticals or bioactive nature products, e.g., corticotropin-releasing factors, chiral arylamines, fluorohexestrol, and (−)-disorazole C1. − Under ambient conditions, all six isomers of 1P1B, 4P2B, and MPE are liquids, and only one enantiomer, S -1P1B, has had its structure crystallographically determined, in S -1P1B@CMOM-3S (Table S4). …”

Effect of Extra-Framework Anion Substitution on the Properties of a Chiral Crystalline Sponge

“…Phenylalcohols and mandelate esters are well-known precursors for the synthesis of a wide range of pharmaceutical drug products . The enantiomers of 1-phenyl-1-butanol (1P1B), methyl mandelate (MM), and ethyl mandelate (EM) are used in the total synthesis of chiral APIs and several bioactive natural products, e.g., corticotropin-releasing factors, (−)-disorazole C1, and renin inhibitors. − Our group has reported the structures of R -1P1B, S -1P1B, and S -MM based on CMOM-3S and CMOM-5­[NO 3 ] , , but the crystal structures of the enantiomers of EM have not been reported in the CSD (Cambridge Structural Database) (Figures S3–S5, Table S1). In this work, we study how anion substitution affects the chiral recognition properties of CMOM-5­[NO 3 ] by substituting NO 3 – with BF 4 – to form CMOM-5­[BF 4 ] .…”

Silver-Catalyzed Tandem Cycloisomerization/[5 + 2] Cycloaddition of 3-Cyclopropylideneprop-2-en-1-ones with Oxidopyrylium Ylides to Form Bibridged Benzocycloheptanones

“…We speculated that an oxidopyrylium ylide-based cycloaddition might be useful for this purpose. This transformation, which was first reported by Hendrickson and Farina in 1980, has become a powerful tool for the construction of cyclic compounds . Typically, the ylide is formed by a thermally promoted or base-promoted elimination reaction of a 6-acetoxy-2 H -pyran-3­(6 H )-one precursor .…”