Chiral tetrahydrofurans

A much more elaborate synthesis of 4-aryl-2-(benzyloxy)carbonyl-3-hydroxy tetrahydrofurans 88 from aryl epoxides requires the use of benzyl diazoacetate. This methodology can now be extended to a highly stereoselective synthesis of chiral tetrahydrofurans starting from optically active epoxides. The mechanism is believed to involve a Williamson-type cyclization as illustrated below <00TL8059>. 

Horner-Wadsworth-Emmons procedures have been used to prepare a variety of compounds including chiral tetrahydrofuran- and tetrahydropyran-deriva-tives/ novel organo-sulfur electron donors containing dithiole and azulene... 

The starting material for the chiral tetrahydrofuran side chain in the conunercial cefovecin sodium synthesis is 2-acetyl-(5)-THF, 18. This material is now commercially available and is manufactured from (5)-THF-2-carboxylic acid 14 obtained by classical resolution technology. Compound 18 provides a convenient stable starting material that can be introduced directly into the synthesis as explained in a later section. 

A highly efficient copper-catalyzed carboetherification of 4-alkenols was reported. Chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products were obtained in high yield and enantioselectivity (14AGE6383). 

A chiral phosphoric acid-catalyzed Petasis-Ferrier-type rearrangement of a seven-membered cyclic vinyl acetal resulted in the formation of a chiral tetrahydrofuran species. It was found that nonclassical hydrogen bonds between the catalyst and the substrate play an important role in controlling the stereoselectivity (14CS3515). 

Goldinonolactone (40) and the chiral tetrahydrofuran (41) were key intermediates in a chiral, but non-carbohydrate-based, synthesis of the antibiotic aurodox both these intermediates are also accessible from carbohydrates, (40) being made from an L—mannose derivative and (41) from D-mannose via a previously described acetyl-... 

An interesting route to chiral tetrahydrofurans with a highly oxygenated branch has been described. 6-Iodo-triben l methyl glycosides (D-gluco, D-manno and D-galacto) were converted to... 

Also in 2009, Belot et al. achieved a tandem reaction combining a secondary amine and a gold complex catalyst for the facile synthesis of densely substituted chiral tetrahydrofurans [47]. The reaction comprised a secondary amine-promoted MichaeladditionandanAu-catalyzedacetalization/cyclizationprocess(Scheme9.53). 

Lei A, He M, Wu S, Zhang X (2002) Highly enantioselective Rh-catalyzed Intramolecular Alder-Ene reactions for thesyntheses of chiral tetrahydrofurans. Angew Chem Int Ed 41 3457-3460... 

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