Cyclohexyl-based Alcohols

Laumen, D. Breitgoff, R, Seemayer, M. P. Schneider, J. Chem. Soc. Chem. Commun. (1989) 148. 

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Monocyclohexyl phosphates and phosphonates can be cleaved by a two-step process in which the ester is treated with an epoxide such as propylene oxide to form another ester, which, upon treatment with base, releases the cyclohexyl alcohol. ... 

An efficient synthesis of optically active pentanedioates is possible using ester enolates based on chiral alcohols. This is illustrated by the addition of the lithium (fl-cnolate of (1 R,2S,5R)-5-methyl-2-(1-methyl-l-phenylethyl)cyclohexyl propanedioate to methyl ( )-2-butenoate at — 100 °C which shows simple and induced diastereoselectivity. 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

Alcohol Electrodes were prepared by layering 20 iL of a saturated solution of N-methyl phenazinium-tetracyanoquinodimethane onto a base graphite electrode. After drying, these electrodes were dipped in N-cyclohexyl-n (2-morpholinoethyl) -carbodimide methylpotoluene sulphonate for 90 minutes. They were then washed in carbonate buffer pH 9.8 and immersed in a solution of alcohol oxidase and peroxidase, and stabilized at various pH values. Electrodes were vacuum dried and stored under vacuum. 

Reaction with P-Donors. In accord with the expectations dis-cussed above, Cp2Mo2(C0K reacts readily with two equivalents of soft nucleophiles, e.g., phosphines, phosphites, CO, etc., to give exclusively the trans-products indicated in eq. 7. With one equivalent of ligand, only disubstituted product (1/2 equiv.) and unreacted 1 (1/2 equiv.) are isolated. Hence, the addition of the first ligand is the slow step (eq. 18). Complex 1 does not react with hard bases, e.g., aliphatic amines, pyridine, ethers, alcohols, or ketones. Bulky phosphines, e.g., (cyclohexyl)3P, and Ph3As or Ph3Sb also fail to react at room temperature. Rather... 

Like the vanadium-based catalysts, the Sharpless AE system intrinsically favors 1,2-anti products this is because the cyclohexyl group in Scheme 8.8a occupies the position denoted by group Ra in Figure 8.2, away from the catalyst. In fact, this diastereoselectivity is somewhat amplified relative to achiral titanium catalysts. When the S allylic alcohol is used with (-f)-DIPT, a matched pair results (Scheme 8.8a). The strong enantiofacial selectivity of the L-(-f-)-DIPT catalyst clashes with the R substrate s resident chirality (this is the case shown in Figure 8.2 with Rb = cyclohexyl). In this mismatched pair, the preference of the chiral catalyst for a attack moderately exceeds that of the allylic alcohol for 1,2-anti product (Scheme 8.8b). The most important consequence is that the latter reaction is 140 times slower than the former. 

The main drawback in Sharpless epoxidation is that the substrate must bear a functional group to achieve the precoordination required for high enantioselec-tivity (as in the case of allyl alcohol). This restriction is not applicable to the epoxidation of alkyl- and aryl-substituted olefins with manganese complexes of chiral Schiffs bases as catalysts. Very high enantioselectivities can be obtained in these reactions (Jacobsen, 1993). The most widely used catalysts that give high enantioselectivity are those derived from the Schiff bases of chiral diamines such as [SiS] and [RR] 1,2-diphenylethylenediamine and [SS] and [RR] cyclohexyl-1,2-diamine. An example is the synthesis of cromakalim. 

Iodide and bromide ions are good nucleophiles but weak bases, so they are more likely to substitute by the Sn2 mechanism than to eliminate by the E2 mechanism. Mechanism 14-1 shows how bromide ion cleaves the protonated ether by displacing an alcohol. In most cases, the alcohol reacts further with HBr to give the alkyl bromide (see Section 11-7). The reaction of cyclohexyl ethyl ether with HBr is an example of this displacement. The cyclohexanol produced by the cleavage reacts further with HBr, and the final products are ethyl bromide and bromocyclohexane. 

Rare earth oxides have been studied to a lesser extent than alkaline earth oxides. However, they show characteristic selectivity in the dehydration of alcohols. Secondary alcohols form 1-olefins, whereas the same reaction over an acid catalyst produces the thermodynamically more stable 2-olefin (312). An example of an industrially important rare earth oxide catalyst is Zr02. It has several applications, including the reduction of aromatic carboxylic acids with hydrogen to aldehydes (314), the dehydration of 1-cyclohexyl ethanol to vinyl cyclohexane (315), and the production of diisobutyl ketone from isobutyraldehyde (316). The extensive use of Zr02 is mainly due to its resistance to poisoning by H2O and CO2, and its inherent catalytic activity is a result of its bifunctional acid-base properties. It contains both weakly acidic and basic sites, neither of which is susceptible to poisoning. The acid-base functionality of Zr02 is displayed in the reaction of alkylamine to nitrile (278) (Fig. 33). To form nitriles from both secondary and tertiary amines, both acid and base sites are required. 

For efficient action of Y as cocatalysts, it is necessary that in reactions with alkyl halides they behave as bases abstracting proton not as nucleophiles entering undesired nucleophilic substitution. From a variety of possible Y-H, only OH acids—alcohols and phenols, and to smaller extent some NH acids—are shown to be proper cocatalysts. In a model studies of base-induced PTC j8-elimination of HBr from cyclohexyl bromide, it was shown that benzyl and benzhydryl alcohols, 2,2,2-trifluoroethanol, trifluoromethylphenyl carbinol, and mesitol are particularly efficient cocatalysts (71) as shown in equation 159. 

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