Cyclopentenes selectivity

A conceptually surprising and new route to prostaglandins was found and evaluated by C.R. Johnson in 1988. It involves the simple idea to add alkenylcopper reagents stereo-selectively to a protected chiral 4,5-dihydroxy-2-cyclopenten-l-one and to complete the synthesis of the trisubstituted cyclopentanone by stereoselective allylation of the resulting enolate. 

The oxidation of simple internal alkenes is very slow. The clean selectiv oxidation of a terminal double bond in 40, even in the presence of an internt double bond, is possible under normal conditions[89,90]. The oxidation c cyclic alkenes is difficult, but can be carried out under selected condition Addition of strong mineral acids such as HCIO4, H2S04 and HBF4 accelerate the oxidation of cyclohexene and cyclopentene[48,91], A catalyst system 0 PdSO4-H3PM06W6Oii(j [92] or PdCF-CuCF m EtOH is used for the oxidatioi of cyclopentene and cyclohexene[93]. 

The cyclohexadiene derivative 130 was obtained by the co-cyclization of DMAD with strained alkenes such as norbornene catalyzed by 75[63], However, the linear 2 1 adduct 131 of an alkene and DMAD was obtained selectively using bis(maleic anhydride)(norbornene)palladium (124)[64] as a cat-alyst[65], A similar reaction of allyl alcohol with DMAD is catalyzed by the catalyst 123 to give the linear adducts 132 and 133[66], Reaction of a vinyl ether with DMAD gives the cyclopentene derivatives 134 and 135 as 2 I adducts, and a cyclooctadiene derivative, although the selectivity is not high[67]. 

Aldol reaction of campholenic aldehyde with propionic aldehyde yields the intermediate conjugated aldehyde, which can be selectively reduced to the saturated alcohol with a sandalwood odor. If the double bond in the cyclopentene ring is also reduced, the resulting product does not have a sandalwood odor (161). Reaction of campholenic aldehyde with -butyraldehyde followed by reduction of the aldehyde group gives the aHyUc alcohol known commercially by one manufacturer as Bacdanol [28219-61 -6] (82). 

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

An interesting strategy for the diastereoselective synthesis of five-membered carbocycles was achieved by the reaction of alkenylcarbene complexes and lithium enolates derived from simple methyl ketones [79]. The use of more or less coordinating solvents (THF or Et20) or the presence of cosolvents such as PMDTA allows the selective synthesis of one or the other diastereoisomer of the final cyclopentene derivative (Scheme 32). 

The photo-induced exo selectivity was observed in other classic Diels-Alder reactions. Data relating to some exo adducts obtained by reacting cyclopentadiene or cyclohexadiene with 2-methyl-1,4-benzoquinone, 5-hydroxynaphtho-quinone, 4-cyclopentene-l,3-dione and maleic anhydride are given in Scheme 4.13. The presence and amount of EtsN plays a decisive role in reversing the endo selectivity. The possibility that the prevalence of exo adduct is due to isomerization of endo adduct under photolytic conditions was rejected by control experiments, at least for less reactive dienophiles. 

The authors chose pyruvic acid as their model compound this C3 molecule plays a central role in the metabolism of living cells. It was recently synthesized for the first time under hydrothermal conditions (Cody et al., 2000). Hazen and Deamer carried out their experiments at pressures and temperatures similar to those in hydrothermal systems (but not chosen to simulate such systems). The non-enzymatic reactions, which took place in relatively concentrated aqueous solutions, were intended to identify the subsequent self-selection and self-organisation potential of prebiotic molecular species. A considerable series of complex organic molecules was tentatively identified, such as methoxy- or methyl-substituted methyl benzoates or 2, 3, 4-trimethyl-2-cyclopenten-l-one, to name only a few. In particular, polymerisation products of pyruvic acid, and products of consecutive reactions such as decarboxylation and cycloaddition, were observed the expected tar fraction was not found, but water-soluble components were found as well as a chloroform-soluble fraction. The latter showed similarities to chloroform-soluble compounds from the Murchison carbonaceous chondrite (Hazen and Deamer, 2007). 

As for cyclopropanation of alkenes with aryldiazomethanes, there seems to be only one report of a successful reaction with a group 9 transition metal catalyst Rh2(OAc)4 promotes phenylcyclopropane formation with phenyldiazomethane, but satisfactory yields are obtained only with vinyl ethers 4S) (Scheme 2). Cis- and trans-stilbene as well as benzalazine represent by-products of these reactions, and Rh2(OAc)4 has to be used in an unusually high concentration because the azine inhibits its catalytic activity. With most monosubstituted alkenes of Scheme 2, a preference for the Z-cyclopropane is observed similarly, -selectivity in cyclopropanation of cyclopentene is found. These selectivities are the exact opposite to those obtained in reactions of ethyl diazoacetate with the same olefins 45). Furthermore, they are temperature-dependent for example, the cisjtrcms ratio for l-ethoxy-2-phenylcyclopropane increases with decreasing temperature. 

A comparative experiment, using WF6/RA1C12 catalyst at Al/W = 1 and Al/W = 5, was carried out at room temperature on a cyclopentene/ 2-pentene mixture (molar ratio of 500/1). The results are summarized in Table II. Notice that the observed molecular weights approach the expected values as the cis selectivity of the catalyst is reduced. 

Table III presents additional cyclopentene polymerization data with 1-pentene as a regulator at 0°C throughout a wide range of conversion. As long as the cis selectivity is maintained, the regulator remains inactive and does not participate in the scrambling process.

The first examples of transition metal-catalyzed [5 + 2]-cycloadditions between vinylcyclopropanes (VCPs) and 7r-systems were reported in 1995 by Wender and co-workers.10 This [5 + 2]-reaction was based conceptually on the Diels-Alder reaction, replacing the four-carbon, four-7r-electron diene with a five-carbon, four-electron VCP (Scheme 1). Although the [5 + 2]-reaction of VCPs and 7r-systems can be thought of as a homolog of the Diels-Alder [4 +21-reaction, the kinetic stability of VCPs (activation barrier for the thermal isomerization of VCP to cyclopentene has been reported as 51.7 kcal mol-1)11 makes the thermal [5 + 2]-reactions involving VCPs and 7r-systems very difficult to achieve. A report of a thermal [5 + 2]-cycloaddition between maleic anhydride and a VCP has been published,12 but this reaction has not been reproduced by others.13 14 Based on the metal-catalyzed isomerization of VCPs to cyclopentenes and dienes,15-20 Wender and co-workers hypothesized that a metal might be used to convert a VCP to a metallocyclohexene which in turn might be trapped by a 7r-system to produce a [5 + 2]-cycloadduct. Based on its previous effectiveness in catalyzed [4 + 2]-21 and [4 + 4]-cycloadditions (Section 10.13.2.4), nickel(0) was initially selected to explore the potential of VCPs as four-electron, five-carbon components in [5 + 2]-cycloadditions. 

Increased ring strain in the C-4 ( = 2) and C-5 (n — 3) products may be a reason for lower yields (and longer irradiation times). The effect of strain on cyclizations is well-documented outside of cycloaromatization chemistry, as well. For example, annealing of a cyclopentene ring leads to a decrease in the cyclization rate and an inversion of the 5-exo/6-endo selectivity for all three patterns shown in Fig. 22. 

The optimized protocol has also been applied to a wide range of open-chain and cyclic dienes (for selected examples, see Table 11.11) [113], The latter generally give higher yields than non-terminal alkenes and cycloalkenes, except for strained ones such as JV-benzyl-pyrroline, cyclopentene, and norbornene (Table 11.10, entries 20—22). 

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). 

Among numerous structural variations of the amino acid ligands that have been examined in this reaction, the lone improvement on proline was reported by Soder-gren and Andersson (107). Rigid bicyclic proline (147) provided a modest improvement in selectivity (65% ee, Eq. 87). Cyclopentene is oxidized under identical conditions providing the cyclopentenyl ester in 54% yield and 60% ee. 

The results of the olefin oxidation catalyzed by 19, 57, and 59-62 are summarized in Tables VI-VIII. Table VI shows that linear terminal olefins are selectively oxidized to 2-ketones, whereas cyclic olefins (cyclohexene and norbomene) are selectively oxidized to epoxides. Cyclopentene shows exceptional behavior, it is oxidized exclusively to cyclopentanone without any production of epoxypentane. This exception would be brought about by the more restrained and planar pen-tene ring, compared with other larger cyclic nonplanar olefins in Table VI, but the exact reason is not yet known. Linear inner olefin, 2-octene, is oxidized to both 2- and 3-octanones. 2-Methyl-2-butene is oxidized to 3-methyl-2-butanone, while ethyl vinyl ether is oxidized to acetaldehyde and ethyl alcohol. These products were identified by NMR, but could not be quantitatively determined because of the existence of overlapping small peaks in the GC chart. The last reaction corresponds to oxidative hydrolysis of ethyl vinyl ether. Those olefins having bulky (a-methylstyrene, j8-methylstyrene, and allylbenzene) or electon-withdrawing substituents (1-bromo-l-propene, 1-chloro-l-pro-pene, fumalonitrile, acrylonitrile, and methylacrylate) are not oxidized. 

The preparation described here of 3-cyclopentene-1-carboxylic acid from dimethyl malonate and cis-1,4-dichloro-2-butene is an optimized version of a method reported earlier3 for obtaining this often used and versatile building block.6 The procedure is simple and efficient and requires only standard laboratory equipment. 3-Cyclopentene-1-carboxylic acid has previously been prepared through reaction of diethyl malonate with cis-1,4-dichloro(or dibromo)-2-butene in the presence of ethanolic sodium ethoxide, followed by hydrolysis of the isolated diethyl 3-cyclopentene-1,1-dicarboxylate intermediate, fractional recrystallization of the resultant diacid to remove the unwanted vinylcyclopropyl isomer, and finally decarboxylation.2>7 Alternatively, this compound can be obtained from the vinylcyclopropyl isomer (prepared from diethyl malonate and trans-1,4-dichloro-2-butene)8 or from cyclopentadiene9 or cyclopentene.10 In comparison with the present procedure, however, all these methods suffer from poor selectivity, low yields, length, or need of special equipment or reagents, if not a combination of these drawbacks. 

A variety of ie.so-epoxidcs could be selectively ring-opened this way with e.e. s as high as 97% [28], The azides can be converted to 1,2-amino alcohols, which are very desirable synthetic intermediates. Surprisingly, the mechanism of the ARO (asymmetric ring-opening) was more complicated than expected [29], First, it turned out that the chloride ion in Cr-salen was replaced by azide. Secondly, water was needed and HN3 rather than Me3SiN3 was the reactant nucleophile. Thirdly, the reaction rate was found to be second order in catalyst concentration, minus one in epoxide (cyclopentene oxide), and zero order in HN3 [30],... 

In 2000 the Miller group provided a proof-of-principle study of Pd pi-allyl chemistry for library selection in the presence of a biomolecule [44]. In this approach, Pd(0) chemistry was employed to generate a library of cyclopentene-1,4-diesters in halogenated solvent (Fig. 1.10). This was allowed to equilibrate across a dialysis membrane with an enzyme target (pepsin) in buffered aqueous solution. LC-MS analysis of the library allowed identification of compound 24 as a library member amplified in the presence... 

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