Cyclization Ferrier carbocyclization

Two synthetically in iortant variants of the Ferrier carbocyclization reaction have been reported. One is a rearrangement of enol acetate 24 (Scheme 12.7). Reaction of 24 with a stoichiometric amount of Hg salt afforded an organomercurial intermediate 25, which was then treated with NaCl to induce the cyclization affording inosose derivatives 26a and 26b with good stereoselectivity. As biologically inportant myo-inositol derivatives, such as d-myo-inositol phosphates, are optically active, the enol-acetate version of the Ferrier carbocyclization would be effective for the preparation of enantiomerically pure inositol derivatives. 

The proposed mechanism of the Ferrier carbocyclization reaction is oudined in Scheme 12.13. First, oxymercuration of the exo-olefin in 48 affords mercurial-hemiacetal 49, whose aglycon moiety (-OMe) eliminates to give mercurial-aldehyde derivative 50. This mercurial intermediate 50 was isolable when a stoichiometric amount of Hg salt was employed at low temperature. Intramolecular aldol-type cyclization of 50 provides product 51. 

The true mechanism of the cyclization process as well as the origin of the diastereoselectivity in the Ferrier carbocyclization reaction has not been fully clarified at present. More detailed investigations will be required for a more conplete understanding of the mechanism of the Ferrier carbocyclization reaction. 

Sugar enol-ethers, which inherently carry both the masked nucleophilic and electrophilic functions, were converted to carbocycles in different reactions. Among the carbocyclization methods the Ferrier (II) cyclization of hex-5-enopyranosides affording six membered carbocycles in the presence of Hg(II) salts is perhaps the most popular one (Scheme 3) [32], This remarkable reaction has provided a practical route to a large variety of bioactive substances such as aminocyclitols [33], pseudosugars [34], inositols [35], and other complex hexitols [36]. 

The Ferrier (II) reaction is quite efficient to form six membered carbocycles, but is unsuitable to prepare cyclopentitols. Five membered enollactone 14 was converted to the cyclopentanone derivative 16 as a single epimer upon treatment by LiAlH(OtBu)3 (Scheme 4) [41]. Spectroscopic studies established some mechanistic details. Accordingly, the hydride of the reducing agent rapidly added to the carbonyl and formed with the metal a stable alu-minate complex. The carbocydization occurred by protonation followed by fragmentation and aldol type cyclization process. 

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