Cyclopentenones addition reactions

The addition of the anions of racemic cyclic allylic sulfoxides to various substituted 2-cyclopentenones gives y-l,4-adducts as single diastereomeric products22. The modest yields were due to competing proton-transfer reactions between the anion and enone. The stereochemical sense of these reactions is identical to that for the 1,4-addition reaction of (Z)-l-(/erf-butylsulfinyl)-2-methyl-2-butene to 2-cyclopentenone described earlier. 

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

Optically active cyclopentanes are useful structural units for many natural products such as steroids, terpenoids, and prostaglandins, but the development of highly enantioselective catalytic 1,4-addition reactions to 2-cyclopentenones has proved to be a challenging goal. Besides the very low stereoselectivities, a major problem with this substrate is the... 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

Similar to the addition reactions of acceptor-substituted dienes (Scheme 16), the outcome of the transformation depends on the regioselectivity of the nucleophilic attack of the organocopper reagent (1,4- vs. 1,6-addition) and of the electrophilic capture of the enolate formed. The allenyl enolate obtained by 1,6-addition can afford either a conjugated diene or an allene upon reaction with a soft electrophile, and thus opens up the possibility to create axial chirality. The first copper-mediated addition reactions to Michael acceptors of this type, for example, 3-alkynyl-2-cyclopentenone 75,... 

Greene, A.E., and Charbonier, F. 1985. Asymmetric induction in the cyclo-addition reaction of dichloroketene with chiral enol ethers. Aversatile approach to optically-active cyclopentenone derivatives. Tetrahedron Lett 16, 5525-5528. 

Catalytic, Enantioselective Addition of Arylboronic Acids to Cycloalkenones. A complex between ligand 1 and a rhodium(I) salt was found to catalyze the asymmetric 1,4-addition reaction of arylboronic acids to cyclohexenone and cyclohep-tenone. The reaction proceeds with high enantiocontrol and excellent yields (eq 4). Lower enantiomeric excesses were observed with cyclopentenone (83% ee), but a variety of substituted phenyl-boronic acids could be used. 

The cycloaddition of the allenes (63) to cyclopentenone results in the formation of the two adducts (64) and (65) in a ratio of 4 1. The addition reaction occurs primarily across the less substituted double bond of the aliens. Cycloaddition of acetylene and but-l-yne to the enones (66) can be brought about using left-circularly polarised light. The resultant cyclobutane derivatives are readily converted to the optically active enones (67). The photoaddition of hex-1-yne to the lactone (68) affords the two isomeric adducts... 

Strategy. A ketone with a substituent group in its position might be prepared by a conjugate addition of that group to an a,j8-unsaturated ketone. In the present instance, the target molecule has a propyl substituent on the /3 carbon and might therefore be prepared from 2-methyl-2-cyclopentenone by reaction with lithium dipropylcopper. 

We reasoned that some cyclic enone sulfoxides should form an even more rigid chelate than that formed from the corresponding acyclic alkenyl sulfoxides when complexed with metal ions model exemplifies the case for a cyclopentenone sulfoxide and suggests a high degree of stereocontrol during the nucleophilic addition reaction. 

Pd-doped organic and carbon aerogels containing between 20 and 40 wt% Pd were demonstrated to be good catalysts in the Mizoroki-Heck reaction of iodobenzene with styrene and 3-butene-2-one in liquid phase to yield franv-l,2-diphenylethylene and frani-4-phenyl-3-butene-2-one, respectively [52], Finally, Eu-doped organic and carbon aerogels were active as catalysts in two Michael addition reactions the reaction of ethyl 2-oxocyclopentanecarboxylate with 2-butenone and with cyclopentenone. Moreover, these catalysts could be recovered and reused [53],... 

This addition reaction provides a route to 3-methylcyclopentenones, since 1,4-diketones are cyclized by base to cyclopentenones. The reaction has been used in a synthesis of c f-jasmone (2). 

Kumamoto, T., Rhine, K., Endo, M. et al. (2005) Guanidine-catalysed asymmetric addition reactions Michael reaction of cyclopentenone with dibenzyl malonates and epoxidation of chalcone. Heterocycles, 66, 347-359. 

Whatever the exact mechanism of the conjugate-addition reaction, it seems clear that enolate anions are formed as intermediates and they can be trapped as the silyl enol ether or alkylated with various electrophiles. For example, addition of lithium methylvinyl cuprate (a mixed-cuprate reagent) to cyclopentenone generates the intermediate enolate 166, that can be alkylated with allyl bromide to give the product 167 (1.161). The trans product often predominates, although the transxis ratio depends on the nature of the substrate, the alkyl groups and the conditions and it is possible to obtain the cis isomer as the major product. Examples of intramolecular trapping of the enolate are known, as illustrated in the formation of the ds-decalone 168, an intermediate in the synthesis of the sesquiterpene valerane (1.162). 

Figure 2.1 Transition states for the Michael addition reaction of malonic ester 61 and cyclopentenone 8 leading to 10(R) (a) and to 10(S) (b and c) and their computed relative energies. (Adapted with p>ermission from Gridnev, 1. D. et al., /. Am. Chem. Soc., 132,16637-16650. Copyright 2010 American Chemical Society.)...

Kumaraswamy et al. reported asymmetric 1,4-addition reactions using chiral calcium complexes prepared from calcium chloride and dipotassium salt of BINOL or Hg-BESfOL (5,5, 6,6, 7,7, 8,8 -octahydro-l,l -bi-2-naphthol) [42-45]. After optimization of the calcium salts and reaction conditions, the calcium catalyst was successfully applied to asymmetric 1,4-additions of malonates or p-ketoesters to a,p-unsaturated carbonyl compounds (Tables 4 and 5) [42, 44]. Among the a,p-unsaturated carbonyl compounds employed in the reactions with malonates, cyclopentenone was found to be a suitable substrate, and high enantioselectivities were obtained (Table 4, entries 3 and 4). In the cases of p-ketoesters, 2-oxocyclopentanecarboxylates are suitable for this reaction, and good yields and good enantioselectivities were observed (Table 5, entries 2, 7, and 8). 

Two important points to note are that the basic reaction mechanism involves the formation of 4.39, a five-membered metallacycle from 4.38 (see Section 2.3.3). This may be considered an oxidative addition reaction as the formal oxidation state of M is zero and 2+ in 4.38 and 4.39, respectively. Second, conversion of 4.39 to 4.40 is the famiUar CO insertion into a metal-carbon bond, which is followed by reductive elimination of cyclopentenone. 

One of the first studies that examined the effect of LAs on diastereose-lectivity in intermolecular radical additions reactions was reported by Torn and coworkers in 1993 (Scheme 10). In the absence of any additive, the addition of Bu radical to the cyclic chiral alkene (R)-(—)-2-((3,5-di-ierf-butyl-4-methoxyphenyl)-sulfmyl)-2-cyclopentenone was found to be relatively unselective, affording diastereomers I and II in roughly equal proportions. However, the inclusion of TiCl2(0 Pr)2 afforded isomer I with... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

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