Cyclopentenols

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

Pentenomycin (33), a highly oxygenated cyclopentenoid with a quaternary chiral center (Scheme 6), was prepared by a similar reaction sequence [29]. The RCM precursor 31 was prepared in eight steps from D-mannose via iodo compound 29 and aldehyde 30 (1 1 diastereomeric mixture). RCM of 31 led to the epimeric cyclopentenols 32. 

The conversion of 27 to chiral hydroxy acid 26 was envisioned to arise via a sequential reduction protocol where the ketone moiety of 27 would enantioselectively be reduced to give chiral allylic cyclopentenol 46 (Scheme 7.11). Subsequent 1,4-addition of hydride to the a,/J-unsaturated ester of 46, presumably assisted by... 

Whereas stoichiometric versions of this strategy were initially reported [43, 44], a catalytic process involving a Ni(COD)2/PBu3 catalyst system, Et3B as reducing agent, and a methanol/THF cosolvent system was recently developed. The process proceeds both inter- and intramolecularly to provide access to a variety of cyclopentenol derivatives (Scheme 22). 

On the other hand, it has been found that the electrochemical reduction is a very unique and useful tool in synthetic organic chemistry when magnesium is used as the material of the electrode. The cathodic reduction of 1,3-dienes with magnesium electrode gives very unique products, i.e. 3-cyclopentenol derivatives when it is carried out in the presence of a carboxylic acid ester (equation 23)17. 

Alkynyl enals cyclize on treatment with a stoichiometric amount of Ni(COD)2/TMEDA complex to give nickel enolates such as 193,436>436a These metallacycles react with electrophiles including methyl iodide and benzaldehyde to yield cyclopentenol derivatives (Scheme 91). 

A variety of enzymes (such as acetylcholine esterase, Porcine pancreatic lipase, Pseudomonas cepacia lipase, and Candida antarcita lipase) have been found useful in the preparation of enantiomerically pure cyclopentenol (+)-2 from 1. The enantiomeric (—)-2 has been prepared from diol 4 by enzymatic acetylation catalyzed by VP-345 with isopropenyl acetate in an organic medium. The key intermediate cyclopentanones (+)-6, (—)-6, 7, and 8, which are useful in the preparation of many bioactive molecules, can be obtained from 3 and 5 via routine chemical transformations.7... 

Moreover, Pd(0)-catalyzed allylations of imidazole with cyclopentadiene monoepoxide led to imidazole-substituted cyclopentenol in moderate yield [54],... 

In 1965, Denney et al. (98) reported the reaction of a number of alkenes with ferf-butyl hydroperoxide (TBHP) and cupric salts of chiral acids. The use of ethyl camphorate copper complex 144 in the allylic oxidation of cyclopentene provides, upon reduction of the camphorate ester, the allylic alcohol in low yield and low selectivity, Eq. 82. The initial publication only provided the observed rotation of cyclopentenol, but comparison to subsequent literature values (99) reveals that this reaction proceeds in 12% ee and 43% yield (based on the metal complex). 

Crimmins reported the synthesis of enantiomerically pure cyclopentenol derivative 8 from diene 6 using ring-closing olefin metathesis followed by treatment with UBH4 [Eq. (6.7)] ... 

As an application of this procedure, Snapper succeeded in the formal total synthesis of (+)-astericanolide. Treatment of iron complex 62, which is prepared from cyclopentenol derivative 60 and iron complex 61, with MeaNO gives fused cyclobutene derivative 63. ROM of cyclobutene of 63 using Ig under ethylene gas smoothly proceeds to produce an eight-membered ring of 64 via Cope rearrangement. The resulting product 64 is converted into Wender s intermediate for the synthesis of (+)-astericanolide ... 

Nevertheless, whereas the base-promoted isomerization of simple linear oxiranes and cyclohexene oxide occurs via a -deprotonation mechanism, recent denterinm-labeUng experiments demonstrate that the LDA-mediated rearrangement of cyclopentene oxide in nonpolar solvents furnishes the corresponding cyclopentenol through an a-deprotonation route (Scheme 7) . 

When both positions a to the C—Li bond of the lithiooxirane have no hydrogen to shift, a 1,2-alkyl shift (Scheme 58) can occur. This rearrangement has been observed recently in the case of oxiranes 125 derived from cyclopentenols. This 1,2-alkyl shift can occur on both sides of the lithiooxirane (Scheme 58, paths a and b). The resulting lithium enolate then undergoes a -elimination process of Li20, leading to diversely substituted cyclopentenones 126 and 127. 

Concerning the possible rearrangement of the lithiooxirane into the alkoxy carbene 155, calculations have also shown that the activation energies of the 1,2-H shifts (to cyclopentanone enolate or cyclopentenol) are extremely high (at least 23 kcalmol" ) from 155, whereas they are much lower (between —0.4 kcalmol" and 8.8 kcalmol" ) from carbene 154. This is explained by a strong intramolecular stabilization of the carbene by the alcoholate moiety, as depicted in Scheme 66. This stabilization could signify that the formation of a carbene from the carbenoid is a disfavored process, and that the carbenoid itself is involved in the rearrangement reaction. 

Recently, interesting examples have been reported of 1,2-alkyl shift (paths a and b in Scheme 58) in the rearrangement of snbstitnted cyclopentenol and -hexenol oxides ... 

Pyrethrinoids are powerful natural insecticides that act on the nervous system of insects. They are esters of chrysantemic acid with a substituted cyclopentenol. The replacement of this motif by a more photochemically stable group affords products that are utilizable in agrochemistry. These compounds exhibit a high insecticide activity and are nontoxic for mammals consequently, they are established in very important markets (e.g., deltamethrin, permethriri). Some fluorinated pyrethrinoids have been synthesized and marketed. One goal of these compounds is to enhance the acaricide activity. Some examples are given in Figure 4.46. 

Absolute configuration of 2-cyclohexcnol is based on chemical correlation whereas absolute configuration of 2-cyclopentenol and the ee of both alcohols are based on their conversion to the corresponding acetates and H-NMR spectroscopy in the presence of Eu(hcf)3. b Entries 1- 4, 6 10 ratio base/epoxide 3 2 entries 4, 11-21 ratio epoxide/base/additive 1 1.5 1.65. 

Asymmetric elimination in epoxycyclopentenones bearing a chiral ketal group 1 with achiral lithium amides to give hydroxycyclopentenones has been examined due to the utility of the latter in prostaglandin synthesis67. When lithium diethylamide in diethyl ether and (3S, 5S )-2,6-dimeth-yl-3,5-heptanediol as chiral auxiliary are used, the diastereomeric cyclopentenol derivatives 2 are obtained in a ratio of 87.7 12.3 in 80 % yield. The absolute configuration is based on chemical correlation and the diastereomeric ratio on GC analysis. No further examples are reported. 

Blechert carried out a tandem reaction of enynes in the presence of olefins instead of ethylene (Scheme 21). Treatment of cyclopentenol derivative 58a with Ic in the presence of an alkene affords 59a. The five-membered ring in estrone 58b is cleaved by Ic to give 59 and an alkene part is introduced on the six-membered C ring. However, cycloalkenyl amine derivative 60 is treated in a similar manner in the presence of an allyl alcohol derivative to give pyrrolidine derivative 61, and in this case, an alkene part is introduced on the diene moiety. Presumably, ruthenium carbene complex XVI reacts with an alkyne part to produce the pyrrolidine ring with a regioselectivity opposite to the other cases. 

Similar treatment of carbonate roc-20 with Pd(0)/L (2 mol%), BPA (3 mol%), and water in CH2CI2 afforded indenol 21 in 88% yield with 97% ee (Scheme 2.1.4.26) [37]. Indenol 21 and cyclopentenol 9d are useful building blocks for the synthesis of an HlV-protease inhibitor and a chiral catalyst for asymmetric Diels-Alder reactions, respectively [38]. 

When allylmagnesium bromide is allowed to react with 3-cyclopentenol, the allylated product (3-allylcyclopentanol) is obtained as an 80 20 mixture of cis- and fraw -isomers (Scheme 67)"°. The reaction of 3-cyclopentenol with diallyhnagnesium in refluxing benzene proceeds slowly but cleanly to yield only the c/5-isomer. 

Allylation of lithium 1-cyclopentenolates.10 In the presence of this Pd(0) complex and 2 equiv. of B(C2H5)3, lithium cyclopentenolate reacts with the (E)-or (Z)-allylic acetate 1 to provide (E)- or (Z)-2 in about 75% isolated yield and... 

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