Cyclopentanol, oxidation

Several procedures for making glutaric acid have been described in Organic Syntheses starting with trimethylene cyanide (28), methylene bis (malonic acid) (29), y-butyrolactone (30), and dihydropyran (31). Oxidation of cyclopentane with air at 140° and 2.7 MPa (400 psi) gives cyclopentanone and cyclopentanol, which when oxidized further with nitric acid at 65—75° gives mixtures of glutaric acid and succinic acid (32). 

It was confirmed, by separating the enzymes in the powder, that many S- and R-directing enzymes do indeed exist in the dried cells. The addition of a coenzyme and cyclopentanol stimulates only an S enzyme because the specific S enzyme can oxidize cyclopentanol (concomitantly reducing NAD(P) ), while other S or R enzymes cannot use cyclopentanol as effectively [14cj. This presents a very interesting case, where the experimental conditions of reduction with a cell having both S-and R-directing enzymes was modified and resulted in excellent S enantioselectivity. 

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. 

The reductive coupling/silylation reaction was extended to more complicated polyenes, such as the triene-substituted cyclopentanol 73, which cyclizes to provide 74 with a 72% yield and 6 1 dr after oxidation (Eq. 10) [44], The reaction is chemoselective the initial insertion occurs into the allyl substituent, which then inserts into the less hindered of the two remaining olefins, leaving the most hindered alkene unreacted. 

Figure 11.1 The hydroboration-oxidation of 1-methylcyclopentene. The first reaction is a syn addition of borane. (In this illustration we have shown the boron and hydrogen both entering from the bottom side of 1-methylcyclopentene. The reaction also takes place from the top side at an equal rate to produce the enantiomer.) In the second reaction the boron atom is replaced by a hydroxyl group with retention of configuration. The product is a trans compound (trans-2-methyl-cyclopentanol), and the overall result is the syn addition of -H and -OH.

The aim of this study is to develop model reaction for the characterization of the acidity and basicity of various transition aluminas, the experimental conditions being close to that for catalysis use. Among various model reactions, the transformation of cyclopentanol and cyclohexanone mixture was chosen for this work. Indeed, this reaction was well known for estimating simultaneously the acid-base properties of oxide catalysts [1], Two reactions take place the hydrogen transfer (HT) on basic sites and the alcohol dehydration (DEH) on acid sites. The global reaction scheme is shown in Figure 1. 

The oxidation of cyclic 2-amino alcohols has been studied.88 In the 2-amino-cyclopentanol series, the ds form was oxidized four times as fast as the trans but, in the 2-amino-cyclohexanol series, the ds form reacted slightly more slowly than did the tram. 

This protocol is also effective for the cyclization of an allenylaldehyde, the synthetic utility of which has been demonstrated in the synthesis of (+)-testudinariol A (Scheme 16.89) [97]. Cyclization of an allenylaldehyde provides a ris-cyclopentanol bearing a 2-propenyl group at the C2 position. The reaction mechanism may be accounted for by coordination of Ni(0) with both the aldehyde and the proximal alle-nyl double bond in an eclipsed fashion with a pseudo-equatorial orientation of the side chain, oxidative cyclization to a metallacycle, followed by Me2Zn transmetalla-tion and reductive elimination. 

Biological. Cyclopentane may be oxidized by microbes to cyclopentanol, which may oxidize to cyclopentanone (Dugan, 1972). 

Some conversion into the anhydrovitamin (112) occurs during silica gel t.l.c. of retinyl palmitate in non-polar solvents. Some new colour reactions of vitamin A are reported to be better than the Carr-Price reaction. The kinetics and mechanism of acid-catalysed isomerization of retinyl acetate into the trans-retro-derivative (113) have been studied. Oppenauer oxidation of kitol (39) results in specific cyclopentanol-cyclopentanone oxidation. ... 

More recently, it was found that the incorporation of N-heterocychc car-bene ligands to the Cp lr moiety (Eq. 12) considerably enhances catalyst activity for alcohol oxidation reactions [50,51]. By way of example, the oxidation of secondary alcohols occurs with high turnovers, up to 3,200 for the oxidation of 1-phenylethanol and 6,640 for that of cyclopentanol (95% yield, 40 °C, 4 h) using the complex with the carbene derived from the tetram-ethyhmidazole (Eq. 12). 

In a very elegant way, Eder performed the regioselective reduction of a dione by treatment with excess of Dibal-H, resulting in the formation of a bisaluminium alkoxide that was selectively oxidized under Oppenauer conditions providing a cyclohexenone, while a cyclopentanol remained unchanged.64... 

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)... 

Ru(III)-catalysed oxidation of p-hydroxyazobenzene (PHAB) by four sodium N-haloarenesulfonamidates show first-order dependences on the oxidant, PHAB and Ru(III), and less than first-order dependence on hydrogen ions. The rates follow the sequence BAB > BAT > CAB > CAT. This effect is attributed to electronic factors.118 Ru(III)-catalysed oxidation of cyclopentanol and cyclohexanol with... 

Mechanisms have been suggested for the N-bromosuccinimide (NBS) oxidation of cyclopentanol and cyclohexanol, catalysed by iridium(III) chloride,120 of ethanolamine, diethanolamine, and triethanolamine in alkaline medium,121 and for ruthenium(III)-catalysed and uncatalysed oxidation of ethylamine and benzylamine.122 A suitable mechanism has been suggested to explain the break in the Hammett plot observed in the oxidation of substituted acetophenone oximes by NBS in acidic solution.123 Oxidation of substituted benhydrols with NBS showed a C-H/C-D primary kinetic isotope effect and a linear correlation with er+ values with p = —0.69. A cyclic transition state in the absence of mineral acid and a non-cyclic transition state in the presence of the acid are proposed.124 Sulfides are selectively oxidized to sulfoxides with NBS, catalysed by ft-cyclodextrin, in water. This reaction proceeds without over-oxidation to sulfones under mild conditions.125... 

The electrochemical reduction of y-oxoesters like 115, synthesized via the cyclopropane route, results in cyclization with participation of the olefinic unitn>. This reaction provides interesting cyclopentanol derivatives, which can be transformed to the corresponding cyclopentenes. Alternatively a fragmentation to medium sized ketones like 116 occurs after saponification and anodic oxidation 77>. 

The norephedrine-derived Masamune asymmetric aldol reaction was utilized in the total synthesis of (+)-testudinariol A (12), a triterpene marine natural product that possesses a highly functionalized cyclopentanol framework with four contiguous stereocenters appended to a central 3-alkylidene tetrahydropyran6 (Scheme 2.2f). The norephedrine-derived ester 13 was enolized with dicyclo-hexylboron triflate and triethylamine in dichloromethane and then treated with 3-benzyloxypropanal to afford the aldol adduct (14) as a 97 3 mixture of anti/syn diastereomers in 72% yield. Diastereoselectivity within the anti -manifold was 90 10. Protection of alcohol as the methoxyethoxymethyl (MEM) ether followed by conversion of the ester to an aldehyde by LiAlELt reduction and subsequent Swem oxidation gave the aldehyde 16 in 64% yield over three steps. 

Working backward, use hydroboration-oxidation to form 2-methyl-cyclopentanol from 1-methylcyclopentene. The use of (1) and (2) above and below the reaction arrow indicates individual steps in a two-step sequence. 

Hypohalites (RO—Hal) are similar to nitrates (see p. 155) in their photochemical behaviour. Ultraviolet irradiation gives an (n,Jt ) excited state that cleaves to form an alkoxy radical and a halogen atom. The radical may undergo alpha-cleavage before recombination with the halogen atom occurs, and this accounts for the formation of 5-iodopentanal (5.69) from the hypoiodite of cyclopentanol such hypoiodites are generated in situ from the alcohol, iodine and mercury(ll) oxide. In open-chain systems the alkoxy radical can... 

Hydroboration/oxidation can also be used to form cyclopentanol. 

The use of resting cells of microorganisms to biotransform organic compounds by specific reactions is a well-established technique. Thus, incubation of norbornanone (12) with a washcd-cell suspension of cyclopentanol grown Pseudomonas sp. NCIB 9872 resulted in the rapid oxidation of the substrate to a mixture of lactones 13 and 14398. 

One gram of platinum oxide catalyst [Org. Syntheses Coll. Vol. 1, 463 (1941) ] is added to a solution of 42 g. (0.50 mole) of cyclopenta-none Org. Syntheses Coll. Vol. 1, 192 (1941) ] in 150 ml. of methanol. The mixture is agitated under a hydrogen pressure of 2-3 atm. until the calculated amount of hydrogen has been absorbed (9-12 hours) [Org. Syntheses Coll. Vol. 1, 66 (1941)]. The catalyst is removed by filtration, and the solution is distilled through a fractionating column. The cyclopentanol is obtained in 93-95% yield (40-41 g.) and boils at 139-141°,... 

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