Cyclohexane Cyclohexanone, enolates

The same authors have shown that independently prepared cyclohexanone enolate on treatment with borane yields trans-cyclohexane-l,2-diol in 45% yield. 2-Methylcyclohexanone, which can give two enolates under appropriate conditions, may thus be selectively converted into either a mixture of trans-diols (112) and (113) in a ratio of 42 58 or the trans-diol (114). Enol silyl ethers may also be employed as substrates for this reaction. 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Organometallic methods, with the possible exception of those involving the stoichiometric generation of enolates and other stabilized carbanionic species 140], have seldom been used in carbohydrate chemistry for the synthesis of cyclohexane and cyclopentane derivatives. The present discussion will not cover these areas. The earliest of the examples using a catalytic transition metal appears in the work of Trost and Runge [41], who reported the Pd-catalyzed transformation of the mannose-derived intermediate 22 to the functionalized cyclopentane 23 in 98% yield (Scheme 10). Under a different set of conditions, the same substrate gives a cycloheptenone 24. Other related reactions are the catalytic versions of the Ferrier protocol for the conversion of methylene sugars to cyclohexanones (see Chap. 26) [40,42,43]. 

As with other intramolecular ene reactions, this reaction is best suited to the preparation of cyclopentanes, but can also be used for the preparation of cyclohexanes. The reaction cannot be used for the formation of cyclopropanes or cyclobutanes since the unsaturated carbonyl compound is more stable than the ene adduct. 8,e-Unsaturated ketones (167) do not give cyclobutanes (171) by enolization to give (170) followed by a type I reaction but instead give cyclohexanones (169) by enolization to give (168) followed by a type II reaction. Alkynes can replace alkenes as the enophile. Enols can be prepared from pyrolysis of enol esters, enol ethers and acetals and from -keto esters and 1,3-dicaibonyl compounds. Tlie reaction is well suited to the preparation of fused or bridged bicyclic and spirocyclic compounds. Tandem ene reactions in which two rings are formed in one pot from dienones have also been described. The examples discussed below 2-i63 restricted to those published since Conia and Le Perchec s 1975... 

Enolates derived from cyclic compounds such as cyclohexane carboxylic acid or cyclohexane carboxalde-hyde generate enolates that are unique. These enolates have an exocyclic double bond that can exist as ( ) and (Z) isomers. The facial and orientational bias in alkylation and condensation reactions of such enolates is influenced by the conformation of the ring it is attached to. Alkylidene cyclohexane enolates show a preference for equatorial attack, just as cyclohexanone derivatives do (sec. 4.7.C,D). 

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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