Cyclopentanol, preparation

Show how each of the following compounds can be synthesized from cyclopentanol and any necessary organic or inorganic reagents In many cases the desired compound can be made from one prepared in an earlier part of the problem... 

How would you prepare the following substances from cyclopentanol More than one step may be required. 

The drug candidate 1 was prepared from chiral cyclopentanol 10 as shown in Scheme 7.3. Reaction of 10 with racemic imidate 17, prepared from the corresponding racemic benzylic alcohol, in the presence of catalytic TfOH furnished a 1 1 mixture of diastereomers 18 and 19 which were only separated from one another by careful and tedious chromatography. Reduction of ester 18 with LiBH4 and subsequent Swern oxidation gave aldehyde 20 in 68% yield. Reductive animation of 20 with (R)-ethyl nipecotate L-tartrate salt 21 and NaBH(OAc)3 and subsequent saponification of the ester moiety yielded drug candidate 1. 

Despite the many simple methods for preparation of carboxylic esters and thioesters, in some instances, use of 1-acylbenzotriazoles 915 as O and S acylating agents may be advantageous. For example, easy to prepare salicylic acid derivative 941 reacts with cyclopentanol under microwave irradiation to give 92% yield of cyclopentyl salicylate in 10 min <2006JOC3364>. In another example, L-phenylalanine derivative 942 reacts with benzyl mercaptan... 

Problem 9.28 Starting with cyclopentanol, show the reactions and reagents needed to prepare (a) cy-clopentene, (b) 3-bromocyclopentane, (c) 1,3-cycIopentadiene, (d) tranj-1,2-dibromocyclopentane, (e) cyclopentane. ... 

In Geotrichum candidum, both an (R)- and an (S)-dehydrogenase are present this was found only when one of the two failed to utilize cyclopentanol to recycle NADP(H) (Matsuda, 2000). Preparation of an acetone powder has already improved enantioselectivity markedly. 

Cyclopentanone is prepared by oxidation of cyclopentanol. Any one of a number of oxidizing agents would be suitable. These include PDC or PCC in CH2C12 or chromic acid (H2Cr04) generated from Na2Cr207 in aqueous sulfuric acid. 

Oxametallacycles are prepared from unsaturated aldehydes or ketones. Oxidative cyclization of 6-hepten-2-one (312) catalysed by the Ti catalyst Cp2Ti to give cyclopentanol 315 has been developed. The key step is the cleavage of the strong Ti—O bond in the oxametallacycle 313 with oxophilic hydrosilane, and the silyl ether 314 is formed with regeneration of Cp2Ti [129,130], Cyclization of 5-hexenal (316)... 

Benzyl chloride is an acceptable starting material, because the problem has specified that we must start with alkyl halides. However, we must still prepare the alkoxide anion. This is the conjugate base of cyclopentanol and can be made by the reaction of the alcohol with sodium metal ... 

The target is now cyclopentanol. Alcohols can be prepared from alkyl halides by reaction with hydroxide ion as the nucleophile. Again, however, the combination of a strongly basic nucleophile and a secondary alkyl halide will result in an unacceptable amount of elimination. A better plan is to treat bromocyclopentane with acetate ion in an aprotic solvent such as DM SO. followed by cleavage of the ester to cyclopentanol ... 

A better hydrogenation catalyst was generated by reaction of alkene metathesis ruthenium catalyst, with sodium hydride, after the RCM reaction was performed. In that case, hydrogenation can be performed under 1 bar of H2 at 20 °C [86]. Thus, cyclopentanols can be selectively prepared in one pot by RCM of the parents dienes, followed by addition of NaH and hydrogenation [86] (Scheme 40). 

We turn next to a study in which it has been possible to pinpoint the factors responsible for asymmetric induction. The reaction in question is one that has been thoroughly investigated in solution by Wagner and coworkers—the photochemical conversion of achiral a-mesitylacetophenone derivatives into chiral cyclopentanols (Scheme 4) [15]. Following our usual protocol, we prepared the para-carboxylic acid derivative 9a and treated this with a series of optically pure... 

A similar reaction has been described for the preparation of thioethers with aryl-and alkylthiotrimethyl silanes.Ring-closure occurs with co-bromo-1,2-epoxyalkanes on the action of magnesium and lithium in the presence of Cul. By this means, cyclobutanol, cyclopentanol, and cyclohexanol can be prepared. (e.g. Eq. 294). 

Due to efforts of Conia s (equation 148) and Trost s groups access to more substituted vinylcyclopropanes has been gained operating with siloxy derivatives prepared either by Simmons-Smith cyclopropanation or using diphenylsulphonium cyclopropylide as a key substance (see Section VI.D.l). Oxidative rearrangement has led to a cyclopentanol... 

The Barbier reaction has been used for the synthesis of alcohols that were difficult to prepare by normal Grignard reagent techniques. This is particularly true for the preparation of cyclic alcohols from halogenated ketones. Several researchers [49-51] have shown that cyclobutanols and cyclopentanols can be prepared in good yields from <5- and y-iodo- and bromoketones in either solvents with Mg or Mg/HgCl2 [Eq. (17)]. 

Vanadium(V) alkoxides have been known since 1913,69 and in Table 2 we show some of the known alkoxides, the parent alcohol, and the nature of the complex in organic solvents and in aqueous solution. Alkoxides have been prepared from methanol, ethanol, isopropanol, t-butanol, silsequioxanes, cyclopentanol, cyclohexanol, norborneol, adamantanol, phenol, and other alcohols (see Table 2).70- 0 The simple complexes associate in organic solvents and dimerization in the presence of alkoxide is observed with the isopropanol complex.70 The more sterically hindred alcohols are less reactive and do not hydrolyze completely in the presence of small amounts of water.73 The first simple alkoxide to be structurally characterized was the methoxide complex (14) and the vanadium was found to be a six-coordinate dinuclear species however, the structure of this compound did not refine very well.91 This was the first report of the diamond core V—O—V—0 unit, albeit associated with two six-coordinate vanadium atoms. The diamond core V—O—V—O (11), which has since then been found to be a typical structural unit for these complexes, was distinctly asymmetric revealing a difference in the interactions between the two mononuclear parts of the molecule. The first monodentate alkoxide found to contain... 

Cyclopentyl chloroformate, C5H9OCOCI. Mol. wt. 148.59, b.p. 69-70,5°/25 mm. The reagent is prepared by the reaction of cyclopentanol with phosgene and has found some use in peptide synthesis for introducing the carbocyclopentyloxy group as... 

Montmorillonite KIO effects regioselective cyclopentylation (68% ori/zo-selectivity) of phenol using cyclopentanol (equation 16). The latter serves as starting material for the preparation of optically active S )-penbutolol, an antihypertensive drug. 

To a solution of l-[l-(trintethylsilyl)cyclopropyl]cyclopentanol [3, R ,R = -(CHjlj- 1.0 g, 4.7 mmol] in dry benzene (75 mL, distilled from CaHj) was added TSOH H2O (150 mg). The mixture was stirred at rt for 4.5 h, treated with sat. aq NaHCOj, and further washed twice with sat. aq NaHCOj, prior to drying (MgS04) and careful solvent evaporation. A colorless oil was obtained yield 0.90 g (99%) which was purified for analysis by preparative vapor phase chromatography. 

Cyclopentyl bromide was prepared in the same way from 86 g. (i mole) of pure cyclopentanol (b.p. 139-140°) and 430 cc. of the hydrobromic-sulfuric acid mixture (1.75 moles hydrobromic acid, 3.5 moles sulfuric add). The product distilled at 75-78°/i2o mm. (w 1.4900) and weighed 133 g. (89 per cent yield). 

A cyclopentanol system is prepared by treating the rigid aldehyde 5 with Lewis acids22. In the presence of titanium(IV) chloride the chlorinated tricycle 6 is formed exclusively in 80-90% yield (Prins-type product), with chlorine in an axial position and a hydroxyl group in the /3-configuration. In a tin(IV) chloride mediated reaction the ene product 7 can be obtained in 42 % yield with the hydroxyl group in the /3-position. 

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