A Straightforward Synthesis of 2,3,4,5-Tetrasubstituted Tetrahydrofuran Derivatives

Abstract

A concise synthesis of 2,3,4,5-tetrasubstituted tetrahydrofurans starting from furan via 7-oxabicyclo[2.2.1]hept-5-ene-2,3-diol (2,3-dihydroxy-7-oxanorbornene) derivatives is reported. The key step of these transformations was the sequence ring-opening metathesis-cross metathesis (ROM-CM) reactions of the oxa­bicyclic compounds in the presence of ethylene and using commercially available 2nd generation Hoveyda-Grubbs catalyst.

Key words

metathesis - tetrahydrofurans - Hoveyda-Grubbs catalyst - oxabicyclic compounds

References

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9

See ref. 6a, p 276 and references therein.

20

Enzymatic desymmetrization of diol 10 by transformation in enantiomerically enriched monoacetate (-)-14 (83%, 92% ee) in the presence of CCL has been reported in ref. 18. In the present report products with different values of ee (not determined) have been used.

21

Enzymatic desymmetrization of diol 11 has been carried out by transformation in enantiomerically enriched monoacetate (-)-23 (83%, 91% ee determined by ^¹9F NMR spectroscopy of the corresponding Mosher’s ester derivative) using enzyme pig pancreatic lipase (PPL). Full details together with determination of the absolute configuration of compounds (-)-14 and (-)-23 are now in progress and will be reported in due course.

22

Commercially available 2nd generation Hoveyda-Grubbs catalyst shows efficiencies similar to 2nd generation Grubbs catalyst but with different substrate selectivity. Specifically it catalyzes RCM, ROM and CM reactions of electron-deficient substrates.