Optically Pure 7-Oxabicyclo[2.2.1]hept-5-en-2-yl Derivatives ("Naked Sugars") as New Chirons

Zinc iodide catalyzed cycloaddition of furan to 1-cyanovinyl (1′S)-camphanate or 1-cyanovinyl (1′R)-camphanate led to optically pure (1R,2S,4R)-2-exo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-yl (1′S)-camphanate and (1S,2R,4S)-2-exo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-yl (1′R)-camphanate, respectively. Saponification afforded (1R,4R)- and (1S,4S)-7-oxabicyclo[2.2.1]hept-5-en-2-one, respectively, allowing concurrent recovery of the chiral auxiliaries, (1S)- and (1R)-camphanic acid, respectively. The 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives ("naked sugars") so obtained can be substituted at C(3), C(5) and C(6) by direct techniques with high stereoselectivity. The methods exploit the exo-facial selectivity of the reactions of these bicyclic systems and the regiochemical control exerted by the remote substituents at C(2) in electrophilic attack at C(5) and C(6). The polysubstituted 7-oxabicyclo[2.2.1]heptan-2-ones so obtained are chirons that can be converted into D- or L-hexose derivatives and analogues, into 2,5-anhydrohexonic acid derivatives (precursors for C-nucleosides and C-glycosides), or into polysubstituted 2-cyclohexen-1-ones. Moreover, conditions have been found under which the bicyclic ethers can be rearranged stereoselectively into polysubstituted cyclopentane-carbaldehydes. Compared with natural carbohydrates, the "naked sugars" are chirons with the following advantages: (1) the problem of selective protection and deprotection of polyalcoholic systems does not exist; (2) the functional moieties are grafted sequentially onto C(3), C(5), and C(6) of the 7-oxabicyclo[2.2.1]heptane systems together with the appropriate protective groups; (3) since both enantiomeric forms of the "naked sugars" are available, either enantiomer of a target compound can be reached with equal ease. 1. Introduction 2. The Carbonyl Group as Homoconjugated Electron-Releasing Substituent 3. Total Synthesis of 2,5-Anhydro-3-deoxy- and -4-deoxy-D-hexonic Acids and Related Deoxyadenosines-C 4. Total Syntheses of ribo-C-Nuleosides 5. De Novo Syntheses of D- and L-Hexoses and Analogues 6. Acid-Catalyzed Rearrangements of 5-exo-6-exo-Epoxy-7-oxa-2-norbornyl Derivatives 7. Stereoselective trans-Amino-hydroxylation of 7-Oxa-5-norbornen-2-one 8. The 7-Oxa-2-norbornanone/2-Cyclohexen-1-one Rearrangement: Total Syntheses of Conduritols 9. Conclusion and Perspectives