Cyclopent 2 enone

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

A similar synthesis starts from commercially available 1,5-hexadiyne and 2-methyl-cyclopent-2-enone. The benzocyclobutene is obtained from a bis-acetylene in a cobalt-catalyzed reaction. It rearranges regio- and stereoselectively to a 3-deoxy steroid derivative. The overall yield from the cyclopentenone was 40% (R.L. Funk, 1977). 

Other catalysts have also been used. In aqueous media, imidazole was found to catalyze Baylis-Hillman reactions of cyclopent-2-enone... 

Within the synthesis of pyrethroids, which are used as insecticides, (5)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-enone is needed. Starting from a racemic mixture of the esterified... 

Regio- and diastereoselectivity in 1,3-dipolar cycloadditions of nitrile oxides to 4-substituted cyclopent-2-enones was studied (238, 239). The reactions are always regioselective, while the diastereofacial selectivity depends on the nature of the substituents. Thus, 4-hydroxy-4-methylcyclopent-2-enone (75) gives preferably adducts 76a, the 76a 76b ratio warying from 65 35 to 85 15 (Scheme 1.22). 

It was also shown that for some other related 4-substituted cyclopent-2-enone derivatives the regiofacial selectivity is lower, and completely reversed in the case of 4-acetoxycyclopent-2-enone, giving 100% of the adduct 77. 

Many methods have been reported for the enantioselective synthesis of the remaining PG building block, the (J )-4-hydroxy-cyclopent-2-enone. For example, the racemate can be kinetically resolved as shown in Scheme 7-28. (iS )-BINAP-Ru(II) dicarboxylate complex 93 is an excellent catalyst for the enantioselective kinetic resolution of the racemic hydroxy enone (an allylic alcohol). By controlling the reaction conditions, the C C double bond in one enantiomer, the (S )-isomer, will be prone to hydrogenation, leaving the slow reacting enantiomer intact and thus accomplishing the kinetic resolution.20... 

The synthesis of the non-racemic cyclopentanone (+)-93 is outlined in Scheme 15. Starting with 2-methyl-cyclopent-2-enone (90), sequential cuprate addition and enolate alkylation afforded the racemic cyclopentanone rac-92 as a single diastereomer. The double bond was cleaved by ozonolysis, the resulting aldehyde chemoselectively reduced in the presence of the keto function and the primary hydroxyl function was subsequently protected as a silyl ether to provide racemic rac-93. This sequence has been applied fre-... 

Ether cleavage and further functionalization afforded the intermediate 268. The [5+2]-cycloaddition provided the hydroazulene 267 with the correct relative configuration at and C. Tracing back the synthesis of the pyryli-um ylide 266 leads to the astonishing realization that 2-methyl cyclopent-2-enone (90) was the original cyclic starting material and that the methyl as well as the isopropyl group were introduced by a sequence of cuprate addition and enolate alkylation (see Schemes 15, 31 and 36 for comparison). 

Conseqnently, the magnesinm chelate 71 can also react as a nucleophilic donor in aldol reactions. In the chemistry involving magnesium chelates, these two aspects model their mode of action as nucleophilic partners in aldol condensations. This is exemplified in aldol condensations of y-diketones . Thus, sodium hydroxyde catalyzed cyclization of diketone 73 to give a mixtnre of 3,5,5-trimethyl-cyclopent-2-enone 74 and 3,4,4-trimethyl-cyclopent-2-enone 75 in a 2.2/1 isomeric ratio (equation 100). When treated with magnesinm methanolate, the insertion of a a-methoxy carbonyl group as control element, as in 76, allows the formation of a chelated magnesium enolate 77, and the major prodnct is now mainly the aldol 78. This latter treated with aqueous NaOH provides the trimethylcyclopent-2-enones 74 and 75 in a 1/49 ratio. 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

Other unsaturated ketones to which allene 2 undergoes cycloaddition include cyclopent-2-enone, l-phenyl-but-2-enone, l,4-diphenyIbut-2-enone, l-phenyloct-2-enone and acrylonitrile in yields ranging from 60 to 92%. The use of a chiral titanium(IV) catalyst gives chiral methylenecyclobutanes 5 with optical yields of at least 94%.2... 

Photocycloaddition of ketene acetals with enones gives cyclobutanes which can be converted to cyclobutanones (see Section 1.3.2.3.). When a chiral ketene acetal was used, photocycloaddition with cyclopent-2-enone gave a low yield of the cycloadduct with only 30% enantiomeric excess.23... 

Irradiation of cyclopent-2-enones in the presence of allenes affords mixtures of 6- and 7-methylenebicyclo[3.2.0]heptan-2-ones, the latter regioisomers being formed preferentially.4,5 From cyclohex-2-enones and allene, 8-methylenebicyclo[4.2.0]octan-2-ones are formed regiose-lectively.6 In contrast, six-membered a,/i-unsaturated lactones and allene afford mixtures of regioisomers.7 Mechanistic arguments for the stereochemical outcome of allene photocycloadditions to steroidal enones have been discussed.8... 

Four-membered rings can be synthesised by [2 + 2] cycloadditions. However, thermal [2 + 2] cycloadditions occur only with difficulty they are not concerted but involve diradicals. Photochemical [2 + 2] reactions are common and although some of these may occur by a stepwise mechanism many are concerted. An example of a [2 + 2] reaction is the photodimerisation of cyclopent-2-enone. This compound, as the neat liquid, or in a variety of solvents, on irradiation with light of wavelength greater than 300 nm (the n - n excited state is involved) is converted to a mixture of the head-to-head (48) and head-to-tail (49) dimers, both having the cis,anti,cis stereochemistry as shown. It is believed that the reaction proceeds by attack of an n - n triplet excited species on a ground state molecule of the unsaturated ketone (Section 2.17.5, p. 106). In the reaction described (Expt 7.24) the cyclopent-2-enone is irradiated in methanol and the head-to-tail dimer further reacts with the solvent to form the di-acetal which conveniently crystallises from the reaction medium as the irradiation proceeds the other dimer (the minor product under these conditions) remains in solution. The di-acetal is converted to the diketone by treatment with the two-phase dilute hydrochloric acid-dichloromethane system. 

The cyclopent-2-enone required for the photodimerisation is prepared by the hydrolysis and oxidation of 3-chlorocyclopentene, which is obtained by the low temperature addition of hydrogen chloride to cyclopentadiene. The latter is obtained by heating dicyclopentadiene. This depolymerisation is an example of a reverse (or retro) Diels-Alder cycloaddition reaction the diene readily reforms the dicyclopentadiene on standing at room temperature. 

Photodimerisation of cyclopent-2-enone. cis,tra.ns,cis-3,3,8-Tetramethoxy-tricyclo[5.3.0.02 6]decane and c s,. ra.ns,c s-tricyclo[5.3.0,02 6]decane-3,10-dione. Place a solution of 49.9 g (0.61 mol) of cyclopent-2-enone in 800 ml of methanol (distilled from solid potassium hydroxide) in a photochemical reactor vessel of 1-litre capacity equipped with a 100-W medium pressure mercury arc lamp surrounded by a Pyrex cooling jacket (Section 2.17.5, p. Ill), flush the magnetically stirred solution with nitrogen for 10 minutes and then irradiate under nitrogen overnight. Filter the white crystalline solid which separates and continue irradiating until no further crystalline material separates from the methanol solution. About 21.5 g of material is obtained after approximately 40 hours irradiation. Crystallisation from methanol gives cis,trans,cis-3,3,8,8-tetramethoxytricyclo[5.3.0.02,6]decane as white plates, m.p. 173-174 °C. The yield is 19.3 g (30%). 

Remove the methanol from the filtrate remaining from the photolysis using a rotary evaporator and remove any cyclopent-2-enone which remains (c. 8.6 g) by distillation under reduced pressure. Several recrystallisations of the residual gum from carbon tetrachloride-hexane followed by a final crys-... 

Haynes, R. K. Starling, S. M. Vonwiller, S. C. Diastereo- and regioselectivity in the reactions of dilithiated allylic secondary amides with cyclopent-2-enone. /. Org. Chem. 1995, 60, 4690-4691. 

Termont, D., De Keukeleire, D., and Vandewalle, M. (1977) Regio- and stereoselectivity in [ 2 + 2] photocycloaddition reactions between cyclopent-2-enone and electron-rich alkenes. Journal of the Chemical Society, Perkin Transactions 1, 2349-2353. 

The first such reaction published in 1908 by Ciamician and Silber was the light induced carvone —> carvonecamphor isomerization, corresponding to type b [1]. Between 1930 and 1960 some examples of photodimerizations (type c) of steroidal cyclohexenones and 3-alkylcyclohexenones were reported [2-5]. In 1964, Eaton and Cole accomplished the synthesis of cubane, wherein the key step is again a type b) photocycloisomerization [6]. The first examples of type a) reactions were the cyclopent-2-enone + cyclopentene photocycloaddition (Eaton, 1962) and then the photoaddition of cyclohex-2-enone to a variety of alkenes (Corey, 1964) [7,8]. Very soon thereafter the first reviews on photocycloaddition of a,(3-unsaturated ketones to alkenes appeared [9,10]. Finally, one early example of a type d) isomerization was communicated in 1981 [11]. This chapter will focus mainly on intermolecular enone + alkene cycloadditions, i.e., type a), reactions and also comprise some recent developments in the intramolecular, i.e., type b) cycloisomerizations. 

Simple diastereoselectivities are observed in the reaction of cyclo-alkenones with cyclic alkenes, e.g., cyclopentene, wherein the transoid tricycle is formed preferentially. Whereas cyclopent-2-enone (7) affords 36 selectively, the more flexible cyclohex-2-enone (8) gives a 3 1 mixture of diastereoisomers 37 and 38 [7,61]. A stereogenic center in the cycloalkenone also has a strong impact on the product ratio as shown for the reactions of 4-alkylcyclohex-2-enones 39 and 40 with acyclic alkenes wherein the major diastereoisomer formed is the one in which the enone-alkyl group is trans to the new ring forming C-C bonds, i.e., 41t and 42t, respectively (Sch. 12) [62,63]. Cycloadducts 42 have been further converted to the pheromone periplanone-B. 

It has been demonstrated that 2-(3,5 -difluorophenyl)-3-(4 -methylsulfonylphenyl)-cyclopent-2-enone (6), which is synthesized by means of a Suzuki reaction (Eq. (14)), displays high selectivity and potency towards cyclooxygenase [36]. 

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