Cycloalkane-1,2-diols

An nnnsnal ring-contraction reaction occnrs on the acid-catalyzed interaction of trimeth-ylhydroqninone 144 with cycloalkane-1,2-diols (e.g. 145) to form the spiro componnds 146 (eqnation 67) . Besides two isomers of cyclohexane-1,2-diols 145, this rearrangement was also described for cyclopentane-, cycloheptane- and cyclooctane-1,2-diols . 

Valuable information on the steric structures for the cis- and trans-cycloalkane-1,2-diols (la) and the cis- and trans-2-aminocycloalkanols (Ib) has been obtained by determining how the Av,oh> values of these compounds vary with ring size. 

Scheme 41.24 Kinetic resolution of trans-cycloalkane-1,2-diols by Schreiner et al.

Schreiner et al. also reported the use of catalyst 76 in conjunction with various carboxyhc acids for the enantioselective Steglich esterification of trows-cycloalkane-1,2-diols [73]. The reaction, which proceeds through the in situ formation of an anhydride, affords high levels of selectivity (s ranging from 6 to >50) and prevents the use of unstable or difficult to access anhydrides (Scheme 41.25). 

In general, thermodynamically stable trans olefins are formed, while cis olefins are obtained in the case of 1,2-dixanthates derived from cycloalkan-l,2-diols. Here, instead of the Bu3SnH/AIBN system, environmentally benign Ph4Si2H2/AIBN, Ph2SiH2/AIBN, and Af-ethylpiperidine hypophosphite/AIBN systems can also be used. As a typically useful method, preparation of D4T (2/,3/-didehydro-3/-deoxythymidine) analogue, which has the same potent anti-HIV activity as AZT, is shown in eq. 7.16. In practice, D2C (2/,3/-dideoxycytidine) and D4C (2/,3/-didehydro-2/,3/-dideoxycytidine) were also prepared by this method [39, 40]. 

Several routes to cycloalkanes have been developed (Fig. 4). Bolton [29] described the synthesis of azabicyclo[4.3, 0]nonen-8-ones using an intramolecular Pauson-Khand cycliza-tion. The relative stereochemistry was controlled in this cyclization step which proceeded in good yield regardless of whether the nitrogen atom bore an allyl (shown) or propargyl (not shown) substituent. The ene reaction was employed in a route to trans-substituted cyclopentane and cyclohexanes [30], Reductive cleavage from the resin with LiBFL, provided the diol or, alternatively, cleavage with Ti(OEt)4 produced the diester. 

The reaction tolerated various functional groups, thus allowing the in situ preparation of allylboron compounds possessing a carbonyl group (Equation (32)).236 The tandem diboration-intramolecular allylboration provided a diastereoselective access to the cycloalkanes bearing 1,3-diols. 

Reductive dehalogenation is an efficient method of synthesis of cyclopropanes spiroannulated to five- and higher-membered carbocycles (i.e. compounds in which spiroannulation does not result in accumulation of extra strain) . The required gem-(dihalomethyl)cycloalkanes are usually prepared by halogenation of the precursor diols (equation 1). The cyclization is most efficiently accomplished in the Zn-alcohol-water system . For example, spiro[2.5]octane 7 was prepared in 91% yield using this procedure. This method is useful even for a one-step preparation of bis-spirocyclopropyl compounds as exemplified in equation 2. However, the application of the reductive dehalogenation method to the synthesis of more strained SPC (i.e. spirohexane or spiropentane) often leads to rearranged products. For example, methylenecyclopentane was the only product obtained from bis(bromomethyl)cyclobutane (equation 3) ... 

Lipase-catalyzed asymmetric hydrolysis has also been conducted on numerous monocyclic, variously substituted five-, six-, and seven-membered cycloalkane and cycloalkene secondary alcohols and diols. More recent reports include cis-4-acetoxyflavan, substituted cyclopentenones, and the 1,2-bis(hydroxymethyl)cyclobutanol derivative exemplified in eq 3. ... 

The regiospecific conversion of cycloalkanes into tertiary trifluoroacetates and esters of 1,2-diols by treatment with ITT [iodine tris(trifluoroacetate)] has been applied to sesquiterpenoids. For example treatment of (8aH)-cedrane... 

The reagent (I) reacts with /ran.r-cycloalkane-l,2-diols to give a multitude of products. Reaction with c/s-cycloalkane-l,2-diols gives /rans-2-chlorocycloalkyl iicetales in high yield. An example is formulated in equation (I). This reaction... 

Vicinal diols undergo oxidative cleavage. There is no apparent steric limitation as both cis- and fra s-cycloalkane-l,2-diols are susceptible to cleavage. However, under certain conditions a-hydroxy ketones may be oxidized without breaking the C-C bond. ... 

The a-, P- or y- cyclodextrins that have been permethylated must be dissolved directly in appropriate polysiloxanes mixtures, and coated on the walls of a glass or fused quartz open tubular columns. The underivatized cyclodextrins, and those that have not been permethylated, can be coated directly onto the walls of the column. Many alcohols, diols, carboxylic acids, alkanes and cycloalkanes can be separated directly on such columns without derivatization. To improve the thermal stability of the mixed stationary phase, a phenylpolysiloxane can be included in the coating material. The presence of phenylpolysiloxane can also improve its stability towards oxidation at elevated temperatures, as cyclodextrin, being basically a sugar, is very susceptible to oxidation at high temperatures. Some methysiloxane, however, must be present to increase... 

Chiraldex B -TA Broad range, alkyl alcohols, halogen acid esters, amino alkanes, amino acids derivatives, halogenated cycloalkanes, certain lactones, diols, alkyl halides, furan and pyran derivatives. 

The peptide catalyst was further applied in the first enantioselective Ste-glich esterification protocol as an alternative pathway for kinetic resolution of tra s-cycloalkane-l,2-diols. Herein, as published by Schreiner and coworkers, a broad variety of carbojgrlic acids could be used as electrophiles in combination with a diimide to perform in situ anhydride formation. With this method comparable yields and high selectivities were obtained as for the above-described method applying an anhydride. 

A -hydroxyphthalimide, a radical catalyst, has been reported to promote the oxidation of various organic substrates such as diols, alkylbenzenes, cycloalkanes and adamantanes by dioxygen under mild conditions . The oxidation takes place both in the absence and presence of Co(a ac)2 or Co(iu ic)3. 

A similar situation exists in the hydroxymercuration and thallium(m) oxidation of cycloalkenes and cycloalkanes, the rate laws showing strict second-order behaviour for both metal ions. In the thallium(ni) reactions two products have been observed, a 1,2-diol and a ketone or aldehyde. Two-electron coupling with trifluoroacetate has been shown to promote oxidative phenol coupling. The mechanism of oxidation of olefins by palladium(n) has been investigated. In the presence of PdClg in aqueous media, the data conform to the rate expression... 

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