FERRIER Chiral cyclohexanone synthesis

FERRIER Chiral cyclohexanone synthesis Transformation of unsaturated glycosides into cyclohexanone derivatives by heating in aqueous acetone with mercury (II) salts. 

Chiral cyclohexanones obtained by the Ferrier carbocyclization reaction are useful precursors for the synthesis of cyclitols and aminocyclitols, some of which are found in clinically important aminoglycoside antibiotics. Additionally, highly substituted cyclohexenones, prepared by the Ferrier carbocyclization followed by (3-elimination, can undergo various further transformations, also making these compounds potential chiral building blocks for the preparation of structurally complex compounds having cyclohexane unit(s). This section provides an overview of the reported synthetic strategies toward various types of natural products based on utilization of the Ferrier carbocyclization reaction. 

The Ferrier carbocyclization reaction, meanwhile, is another iii5)ortant carbohydrate-based transformation in organic synthesis. The reaction is highly effective for the conversion of readily available aldohexoses into enantiomerically pure cyclohexanones. Chiral and highly functionalized cyclohexanones obtained by the Ferrier carbocyclization are potentially useful chiral building blocks, so the reaction has been frequently employed in the synthesis of structurally complex natural products containing a cyclohexane unit. In this chapter, we will focus on the Ferrier carbocyclization reaction and its applications to natural product S5mthesis. 

The Ferrier carbocyclization reaction of an enol-acetate substrate gives an a,p-dihydroxy-cyclohexanol derivative (see Schemes 12.7 and 12.81. This transformation would be effective for the chiral synthesis of inositol derivatives. A retrosynthetic plan for the marine natural product tetrodotoxin 88 based on the enol-acetate version of Ferrier carbocyclization is shown in Scheme 12.22. Tetrodotoxin 88 was planned to be synthesized from lactone 89, the precursor of which would be highly functionalized cyclohexane 90. Cyclohexane 90 was envisioned to arise from cyclohexanone 91. For the preparation of 91, Ferrier carbocyclization of enol acetate 92 would be a suitable transformation. d-Glucose derivative 93 possessing an exo-methylene at C-3 would serve as a promising precursor of 92. 

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