Cyclopentenes, 1-acyl

Bifunctional molecules undergo intermolecular cyclizations with enamines through simple alkylations 112-114) and acylations 115). For example, the reaction between l-(N-pyrrolidino)cyclopentene and 1,4-diiodobutane produces, after hydrolysis, ketospirans 92 and 93 113). 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

In fluorosulfonic acid the anodic oxidation of cyclohexane in the presence of different acids (RCO2H) leads to a single product with a rearranged carbon skeleton, a 1-acyl-2-methyl-1-cyclopentene (1) in 50 to 60% yield (Eq. 2) [7, 8]. Also other alkanes have been converted at a smooth platinum anode into the corresponding a,-unsaturated ketones in 42 to 71% yield (Table 1) [8, 9]. Product formation is proposed to occur by oxidation of the hydrocarbon to a carbocation (Eq. 1 and Scheme 1) that rearranges and gets deprotonated to an alkene, which subsequently reacts with an acylium cation from the carboxylic acid to afford the a-unsaturated ketone (1) (Eq. 2) [8-10]. In the absence of acetic acid, for example, in fluorosulfonic acid/sodium... 

Upon fonnation of intermediate LI, conjugate addition to a chalcone and subsequent proton transfer is proposed to lead to enolate LIII (Scheme 37). An intramolecular aldol addition provides activated carboxylate LIV in which alkoxide acylation regenerates the catalyst and delivers p-lactone LVI which, upon decarboxylation, gives rise to a trisubstituted cyclopentene. 

In 2007, Scheldt and co-workers reported the intramolecular desynunetrization of 1,3-diketones utilizing triazolinm pre-catalyst 249 (Scheme 39) [129], Generation of a homoenolate is followed by P-protonation and aldol reaction. In accordance with the proposed mechanism by Nair (Scheme 37), acylation occurs followed by loss of carbon dioxide. Cyclopentenes are formed in enantioselectivities up to 94% ee. The scope of this reaction is limited to aryl substitution of the diketone and alkyl substitution of R. 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

From a preparative point of view, the acylation of ketones via enamines is of particular interest. In comparison with pyrrolidine and piperidine enamines, the less reactive morpholine enamines give better yields, as found by Hiinig et al.2iZ j8-Diketones are the products of acylation with an acyl halide followed by acid hydrolysis, whereas with ethyl chloroformate, /J-ketoesters are obtained.212 Hiinig and his collaborators242-247 have used the acylation of 1-morpholino-l-cyclopentene and 1-morpholino-l-cyclohexene to lengthen the chains of acids by five and six carbon atoms, respectively. The reaction may... 

Asymmetric Acylation of me o-Diols. Both cyclic and acyclic me o-1,2-diols are desymmetrized by acylation in the presence of a stoichiometric amount of this ligand with modest-to-excellent enantioselectivity (eq 4). In a special case, cis-5,5-dimethyl-2-cyclopentene-l,4-dior was monobenzoylated in the presence of a catalytic amount of this ligand in good yield and with perfect enantioselection (87%, >99.5% ee). 

A major disadvantage with the acylation method is that the starting material, cis-cyclopentene-3,5-diol, is not readily available and must be... 

Coumarin has been studied extensively in this context in the absence of a sensitiser, it gives a syn head-to-head dimer in the presence of benzophenone as sensitiser, the anti isomer is formed the syn head-to-tail dimer is obtained by irradiation in acetic acid. Cyclobutane-containing products are obtained in modest yields by sensitiser-promoted cycloadditions of coumarins or 3-acyl-oxycoumarins, with alkenes, ketene diethyl acetal or cyclopentene. ... 

Hydride transfers are implicated in several acylations of alkynes by saturated acyl chlorides leading to cyclopentenes. Intramolecular [1,5] hydride shifts have been shown to be a common feature in silver-assisted reactions of cyclohexanylcarbonyl chloride with alkynes.The nature of the final product depends on the structure of the resulting cation. Capture of fluoride ion, ring contraction and acyl or alkyl migrations of axial substituents have been observed (Scheme 24). 

The reactions of alicyclic olefins with Se02 have been extensively investigated. Heating cyclopentene with Se02 in acetic anhydride (acylating oxidation) oxidizes it to much monoacetoxy- and a little diacetoxy-cyclopentene but in a bomb tube at 90-100° much diacetate and little monoacetate are obtained.225 Thus the second methylene group next to the double bond is more or less attacked according to the reaction conditions. 

The fluorescence quantum yields of pyrene-1-carboxaldehyde in water and methanol are 0.98 and 0.07/ an effect attributed to solvent effects on 7c,n and n,n states. Cycloaddition reactions of 1-naphthonitrile to 1,2-dimethyl-cyclopentene are attributed to both and Lj, states.It is pointed out that although dual fluorescence is known, this is the first example of divergent reaction from two nearly isoenergetic singlet states. An analysis of the u.v. spectra of some acyl pyridines, including a theoretical examination of the molecular geometry, and excited states of bipyrimidine compounds have also been made. Photo tautomerism and the fluorescence of the cation of 4-amino-pyrazole[3,4-iflpyrimidine, an analogue of adenine, has been published by Wierzchowski et Intramolecular heteroexcimer formation in... 

Ketals 201 from cyclopentenone and dialkyl tartrates have a rigid cyclopentene ring. Submitted to 2 -i- 2 photocycloaddition with a cyc-lohexenone and a cyclopentenone carboxylic ester, diastereoselectivities of up to 84% were obtained. The selectivity was very sensitive to the steric hindrance of the chiral auxiliary and tartrate derivatives gave better results than the corresponding threitoldibenzylethers [162]. When the chiral auxiliary was introduced into an acylic enone system (204), the diastereoselec-tivity of the cycloaddition was low. This indicates that the chiral alkene in the ground state exists as a mixture of conformers leading to opposite facial diastereoselection [163]. 

Chemical resolution of a meso-elio/. Acylation of the symmetrical meyo-diol ciy-2-cyclopentene-l,4-diol (2) with 1 equiv. of the chiral reagent 1 in pyridine affords a mixture of the monoesters 3 and 4 in 517 yield, together with some of the diester. The mono esters were separated readily by fractional crystallization to give pure, optically active 3 and 4. These esters were converted into the (+ )-and ( —)-5 hydroxy ethers, respectively, and then into the optically active lactones ( + )- and (—)-6 by Claisen rearrangement and lactonization (6, 608-609). These lactones have been converted into both natural and unnatural prostaglandins. See scheme (I) at top of page 321. 

Cyclopentene derivatives. These compounds are formed by reaction of 1 in the presence of TiCU with aldehydes, ketones, -keto esters, or o(, 8-unsaturated ketones. The allylsilane reacts with acyl chlorides in the presence of AICI3 to form cyclopentene-2-yl ketones, which are rearranged on silica gel to the a,/S-unsaturated ketones. ... 

Scheldt and co-workers reported a cooperative eatalysis process integrating Ti and triazolium-derived NHCs, providing a facile synthesis of cis cyclopentenes with a broad substrate scope. Using the cooperative system that successfully integrates Lewis acid catalysis and NHC catalysis, previously inaeeessible substituted cyclopentenes were provided directly with excellent levels of enantio- and diastereoselectivity (up to 81% yield, 99% ee). The addition of 2-propanol might facilitate the disassociation of the tertiary alkoxide, and therefore accelerate the acylation step to regenerate the NHC catalyst and Ti(0 Pr)4 (Scheme 7.54). 

Recently, the Biju group demonstrated a highly enantioselective NHC-eatalyzed synthesis of functionalized cyclopentenes via o,p-unsaturated acyl azolium intermediates. This organo cascade reaetion of modified enals with malonic ester derivatives having a y-benzoyl group involves the Michael/ intramolecular aldol/p-lactonization/decarboxylation sequence to deliver functionalized cyclopentenes in good yields and excellent ee values (up to 85% yield and >99% ee) (Scheme 7.105). 

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