Cyclopentadiene Cycloaddition with ketene

Staudinger observed that the cycloaddition of ketenes with 1,3-dienes afforded cyclobutanones from a formal [2+2] cycloaddition [52] prior to the discovery of the Diels-Alder reaction. The 2+2 cycloadditions were classified into the symmetry-allowed 2+2 cycloaddition reactions [6, 7], It was quite momentous when Machiguchi and Yamabe reported that [4+2] cycloadducts are initial products in the reactions of diphenylketene with cyclic dienes such as cyclopentadiene (Scheme 11) [53, 54], The cyclobutanones arise by a [3, 3]-sigmatropic (Claisen) rearrangement of the initial products. 

The most nucleophilic atom on the diene adds to the most electrophilic atom on the ketene and the cis geometry at the ring junction comes from the cis double bond of cyclopentadiene. It is impressive that even this excellent diene undergoes no Diels-Alder reaction with ketene as dienophile. The [2 + 2] cycloaddition must be much faster. 

S.2 Cycloadditions Involving Ketenes We next present two examples of cycloadditions involving ketenes that invoke a bifurcating PES. The cycloaddition of ketene with cy clopentadiene had long been thought to simply give the formal [2-1-2] product, such as the reaction of cyclopentadiene 67 with dichloroketene 68... 

Ussing, B. R. Hang, C. Singleton, D. A. Dynamic effects on the paiselectivity, rate, isotope effects, and mechanism of cycloadditions of ketenes with cyclopentadiene, J. Am. Chem. Soc. 2006, 725, 7594-7607. 

Like ketenes, allenes generally undergo [2 + 2] cycloadditions with alkenes affording methylene cyclobutanes . In reactions with 1,3-butadienes, both Diels-Alda- adducts and [2 -F 2] cycloadducts are formed. Cyclopentadiene, however, has been reported to react with several allenes to give exclusively Diels-Alder adducts. From the sevraal possible mechanisms by which [2 -F 2] cycloaddition reactions of allenes could occur,... 

Note also the preference for [2 + 2] rather than [2+4] cycloaddition with cyclopentadiene. A computational comparison of the [2 + 2] and [2 + 4] modes of reaction between cyclopentadiene and ketene found the former to have a lower (by about... 

Nitroethene and vinyl sulfoxides have also been employed as ketene equivalents. Nitroethene is an excellent dienophile and oxidation of the initial nitro-adduct gives the corresponding ketone. However, the thermal instability of nitroethene limits its appUcation to cycloadditions with reactive dienes. An attractive feature of vinyl sulfoxides as ketene equivalents is that they can be obtained in optically active form because of the chirality of the sulfoxide group, thus allowing enan-tioselective Diels-Alder reactions. Cycloaddition of p-tolyl vinyl sulfoxide with cyclopentadiene requires heat and gives a mixture of all four (two exo and two... 

Bicyclo[3,2,0]heptane Derivatives.— These are principally prepared by the [2 -I- 2] cycloaddition of a cyclopentene with another unsaturated unit. Typical combinations which have been routinely applied in syntheses are photochemical addition of a cyclopentene to an olefin or acetylene and thermal addition of a cyclopentadiene with an olefin, a keten, or an acetylene. In the last case, cycloaddition with an alkyne is complicated both by competition between [2 -h 2] and [2 + 4] modes of addition and by the possibility of a second addition of cyclopentadiene to the initially formed bicyclo[3,2,0]heptadiene. The results for diphenylacetylene and cyclopentadiene are shown in Scheme 31. 

The use of ketene equivalents in 4- -2-cycloaddition reactions for organic synthesis has been reviewed. " a-Carbonyl ketenes behave as dienes in Diels-Alder reactions with 4-aryl-2-methyl-2,3-dihydro-l,5-benzothiadiazepines to yield regiospecific cycloadducts. The reactions of diphenylketene with cyclic ( -cw)-l,3-dienes such as cyclopentadiene and cyclohexadiene initially yield the Diels-Alder adducts, which are converted into the Staudinger cyclobutanones by [3,3]-sigmatropic rearrangementsl-Benzyl-l,3-diazabuta-l,3-dienes react with ketenes to produce the 4 - - 2-cycloadducts, substituted l-benzyl-4-(benzylidenimino)-4-phenylazetidin-2-ones, which rearrange into the more stable 5,6-dihydro-3//-pyrimidin-4-ones. The formal 4 - - 2-cycloaddition reaction of ketenimines has been used to synthesize benzoimidazo[l,2-Z ]isoquinolines. ... 

Keten-olefin [2 + 2] cycloadditions have received considerable attention recently The isomer with the larger keten substituent (L) in the endo position (293) is found in addition of keten to cyclopentadiene. This is predicted from the orthogonal keten-olefin transition state [2, + 2 ] of Woodward and Holfman. This model also accounts for the reduced reactivity towards ketens of /rofts-butene compared with cw-butene. Methylbromo-and methylchloro-keten undergo cycloaddition with a wide variety of olefins with only small variation in the endoiexo ratio, i.e. the ratio of (295) (294)... 

A key transformation in Corey s prostaglandin synthesis is a Diels-Alder reaction between a 5-(alkoxymethyl)-l,3-cyclopenta-diene and a ketene equivalent such as 2-chloroacrylonitrile (16). As we have already witnessed in Scheme 3, it is possible to bring about a smooth [4+2] cycloaddition reaction between 5-substituted cyclopentadiene 15 and 2-chloroacrylonitrile (16) to give racemic 14 as a mixture of epimeric chloronitriles. Under these conditions, the diastereomeric chloronitriles are both produced in racemic form because one enantiotopic face of dienophile 16 will participate in a Diels-Alder reaction with the same facility as the other enantiotopic face. In subsequent work, Corey s group demonstrated that racemic hydroxy acid 11, derived in three steps from racemic 14 (see Scheme 3), could be resolved in a classical fashion with (+)-ephe-... 

The replacement of ring C by a cyclic anhydride ring could be looked upon either as elimination of ring C or replacement of the ring by a heterocyclic anhydride ring. In any case, Fields et al. showed that quinolizinium 2,3-dicarboxylic acid anhydride (37) underwent cycloaddition reactions with either cyclopentadiene or styrene to alFord the expected products (e.g., 38). The 2,3-dimethylquinolizinium ion did not undergo cycloaddition even with the more reactive ketene diethylacetal. 

The cycloaddition reactions of ketenes with cyclopentadiene have been known to give formal [2 + 2] cycloadduct (35) instead of [4 + 2] Diels Alder products (34) (Scheme 8). A combined computational and experimental study suggested that the reaction initially gives [4 + 2] cycloadduct, which subsequently rearranges to 35 via [3,3] sigmatropy.91,92 The MP2/6-31G //HF/3-21G calculations... 

The (2 + 2) cycloaddition reactions of ketenes with alkenes are synthetically useful routes to cyclobutanones. Ketenes are particularly useful due to the low steric hindrance at the carbonyl carbon. An example is the reaction of dichloro-ketene with cyclopentadiene which, after reductive dechlorination of the product, gives bicyclo[3.2.0]hept-2-en-6-one (Expt 7.25). 

Nor shall we discuss reactions of highly reactive intermediates such as carbocations, carbanions, ketenes (such as 14), or benzynes that are always prepared in the presence of the molecule with which they are to react. This 2 + 2 ketene cycloaddition 15 actually involves three steps but the ketene is very reactive and cyclopentadiene must be present when it is formed if a good yield of the important adduct 16 is to be had. 

However, the equivalent of 49 is known from the reaction of diphenyl ketene with cyclopentadiene. The adduct 50, formed at low temperature, rearranges through [3,3] sigmatropic shift to form what appears to be the [2 + 2] adduct 51. The reaction of 1-methoxybutadiene with diphenyl ketene to form 52 at low temperature is akin to [2 + 2] reaction involving nc=c of the ketene. However, this species also rearranges further by [3,3] sigmatropic shift to form 53, which is akin to [4 + 2] cycloaddition of the butadiene with 7rc=o °f the ketene, just as in 49 [ 18]. 

Cycloaddition of a monosuhstituted ketene with cyclopentadiene can give two diastcrcomers. The more hindered ent/o-isomer is usually formed preferentially or exclusively. The isomer with the larger substituent endo is formed selectively in the cycloadditions of unsymmetrical disub-stituted ketenes with cyclopentadiene9. 

The reported thermal [4 + 2] cycloaddition of arylmethylenemalon-dialdehydes with electron-rich olefins including enol ethers, ketene acetals, enamines, and cyclopentadiene (benzene, 25°C) or their Lewis acid-catalyzed reaction with simple olefins including isobutylene and 1,1-diphenylethylene (Znl2 catalyst, benzene, 25°C) further illustrates the Diels-Alder rate acceleration accompanying the substitution of an ,/3-unsaturated aldehyde with a C-3 electron-withdrawing group [Eq,... 

The [4+ + 2] cycloadditions proceed in a regiospecific manner with the nucleophilic carbon of the electron-rich dienophile attaching to the expected electrophilic site of the aromatic quaternary salt (e.g., C-6 for acridizinium salts, C-l for isoquinolinium salts) and the rate of reaction (ketene aminals, ketene acetals, enamines > cyclopentadiene > 2,3-di-methylbutadiene > styrene > dihydropyran > 2-butene > maleic anhydride) does increase as the nucleophilic character of the dienophile is enhanced [Eq. (66)].l48e 149... 

DicWoroketene is particularly reactive, and reductive dechlorination of the product with zinc and acetic acid allows access to the cyclobutanone from formal addition of ketene itself. Thus, cycloaddition of dichloroketene with cyclopentadiene, followed by dechlorination and Baeyer-Villiger oxidation gave the lactone 173, a usehil precursor to various oxygenated cyclopentane products (3.117). Intramolecular cycloaddition reactions of ketenes can allow the formation of bicyclic and polycyclic products using otherwise unstable ketene intermediates. ... 

Ketene itself is usually made by high-temperature pyrolysis of acetone but some ketenes are easily made in solution. The very acidic proton on dichloroacetyl chloride can be removed even with a tertiary amine and loss of chloride ion then gives dichloroketene in an ElcB elimination reaction. If the elimination is carried out in the presence of cyclopentadiene a very efficient regio- and stereospecific [2 + 2] cycloaddition occurs. 

The cycloaddition of diphenylketene with cyclopentadiene is a classic reaction in ketene chemistry that has long been studied, but the interpretation of this... 

The first reported examples of Lewis acid-catalyzed ketene-alkene [2+2] cycloadditions provide efficient and diastereoselective routes to cyclobutanones (Scheme 7.53). In this procedure, the alkene is added to a ketene solution generated by dehydrochlorination but is not reactive until the mixture is added to the catalyst solution. Catalyzed reactions with conjugated alkenes such as cyclopentadiene favor the opposite diastereoselectivity to that of the corresponding thermal reactions. 

The stereochemistry of ketene cycloadditions has been a longstanding subject of interest, and the preferences for [2 - - 2] and [4 4- 2] cycloadditions of dihaloketenes with cyclopentadiene (Scheme 4.27) have been compared using various computational methods. ... 

Huisgen has also studied the effects of substitution in the keten in the reactions of a series of alkylphenyl ketens to ethyl cis- and trans-propenyl ethers. With the cis-enol ethers the thermodynamically less stable cyclobutanone is always produced. This is the same result as that found in the addition of ketens to cyclopentadiene and other cis-olefins, and the mechanistic implications are the same. With the trans-enol ether, the thermodynamically more stable product is formed, and this observation can be rationalized in terms of a [tc2 + k2 J cycloaddition if the preferred orientation complex has the substituent on the keten between the alkoxy-group and a hydrogen rather than between a methyl group and a hydrogen on the enol ether. In all the cases studied, the cis-enol ether reacted more rapidly than its trans-isomer. This cis trans reactivity ratio is not found in [2 + 2] additions proceeding via zwitterionic intermediates. For example, the rate ratio for the reaction of TCNE with cis- and trans-1-alkenyl ethers is very close to unity. 

Dienes, such as cyclopentadiene, are often used to trap the more reactive ketenes, which otherwise would undergo oligomerization or polymerization reactions. In the reactions of monoketenes with cyclopentadiene endo cycloaddition products are usually obtained, with the exception of t-butylketene, where the exo adduct is predominantly formed . In the reaction of MeC(X)=C=0 (X = Cl, Br) with cyclopentadiene, a strong solvent effect on the exo/endo ratio is observed . The more polar solvents favor the exo isomer, indicating the presence of a polar intermediate. 

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