Carbocyclic derivatives cyclohexane synthesis

Review coverage of the chemistry involved in the synthesis of enantiomerically pure natural products from carbohydrates is now extensive [2]. It is relevant to note that whereas, in 1983, the numbers of carbocyclic target compounds were relatively limited, as outlined in an authoritative monograph written by Hanessian [3], a comprehensive review of the methods available for making cyclopentane and cyclohexane derivatives from carbohydrates published 10 years later [4] cited 338 references, more than 80% of which were dated 1980 or later. The attention afforded the synthesis of carbocyclic products also features prominently iu a 1993 review of the use of sugars in the preparation of enantiomerically pure natural products [2],... 

In much the same way as synthesis of their cinnoUne counterparts (see Chapter 1), the primary synthesis of phthalazines (or hydrophthalazines) may be done by cyclization of benzene (or cyclohexane) derivatives already bearing appropriate substituents, by cyclocondensation of benzene (or cyclohexane) derivatives with acyclic synthons that provide one or more of the ring atoms needed to produce the phthalazine system, by analogous processing of other carbocyclic or pyridazine substrates, or by modification of other heterocycUc substrates in various ways, lypical pre-1972 examples in each category of synthesis may be found from cross-references to Simpson s volume (e.g., H 72) or to Singerman and Patel s volume (e.g., E 333) that appear in some section headings. A variety of pre-and post-1972 syntheses have also been reviewed elsewhere. ... 

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. 

In 2010, the Sato group disclosed the synthesis of tetrodotoxin 86 starting from d-glucose, in which the Perrier carbocyclization of enol acetate 92 was employed for the construction of the cyclohexane core of tetrodotoxin. 4,6-O-Benzylidene derivative 99 was converted into pyranoside 93 possessing an exo-methylene group at C-3 (Scheme 12.47). m-CPBA oxidation of 93 stereoselectively provided epoxide 183. Alkaline hydrolysis of the epoxide in 183 followed by acetonide formation gave primary alcohol 184. Oxidation of 184 afforded aldehyde 185, which was converted into (Z)-enol acetate 92 by the action of acetic anhydride and potassium carbonate. When enol acetate 92 reacted with Hg(OAc)2, followed by NaCl treatment, the Perrier carbocyclization reaction successfully took place to afford a mixture of... 

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