Ketene reaction with cyclopentadiene

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. 

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... 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

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). 

Model the reaction between ketene and cyclopentadiene using FO theory, and confirm your model by optimizing the approach (do not calculate the transition state). Show that a Diels-Alder reaction with the CC bond, although theoretically possible, is improbable. 

Ketene acetal sulfoxide 30 has been used as a chiral ketoester ketene acetal equivalent, because it undergoes a ready enantiocontrolled reaction with cyclopentadiene at -78°C in the presence of BF3 yielding a 96 4 mixture of endo and exo adducts with complete n-facial selectivity (Scheme 15) [44]. The endo selectivity decreased with other catalysts, but the 7r-facial selectivity remained complete, whereas under thermal conditions (139 °C, 15 h) a mixture of the four possible adducts was obtained. The adduct 31 was transformed into (+)-(lRy4R)-norbornenone in a four-step sequence. 

In the reaction with cyclopentadiene, the PC double bond in a,b acts as the ene component (62). A 1-diamino-substituted 2-phospha-l,3-butadiene could be synthesized by reaction of the ketene with the phos-phaalkene [Eq. (36)] (87). 

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... 

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,... 

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,... 

Reaction of ketene with cyclopentadiene proceeds in a [2-1-2] rather than a [2- -... 

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. ... 

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. 

Diazocyclopentadienes lose nitrogen by the action of light or heat, generating carbene species, whose reactions with alkenes and with other caibene acceptors have been extensively studied. Cyclo-pentadienylidene has been directly observed in a photolysis of diazo-cyclopentadiene at very low temperature in a matrix [83,84]. IVhen warmed it dimerised or reacted with carbon monoxide present in the matrix to give a ketene ... 

Computational studies of the Diels—Alder reaction of cyclopentadiene with ketene at the C=0 and C=C bonds were used for comparison to the corresponding reactions of allene and ketenimine. The reactivities were dependent on the distortion energy arising from the folding energy and molecular strain, and the interaction energy from orbital interaction, closed-sheU repulsion, and static repulsion (Eqn (4.105)). ... 

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. ... 

Private communication from Professor J. R. Johnson, Cornell University, and taken from the doctoral thesis of J. M. Witzel, entitled "Dimethyl Ketene and Its Reaction with Cyclopentadiene," 1941. 

In the catalyzed thermal reaction of alkylarylketenes with cyclopentadiene [4+2] cycloadducts are obtained (see Section 4.1.4.2). In this reaction, the ketene undergoes the reaction across its C=0 bond initially, but the isolated cycloadducts derive from addition across the C=C bond. In contrast, olates, such 6-oxo-3,6-dihydro-l-pyrimidinium-4-olates 377, react with dimethyl- and diphenylketene across the C=0 bonds to give the stable... 

Illustrate how the following reagents could serve as ketene equivalents for use in Diels-Alder reactions with 1,3-cyclopentadiene. (Prostaglandins-6)... 

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. 

Observation of the list of borazine derivatives produced photochemically (Table 3) reveals that all of the reagents yielding photochemical products have an electronegative element (either 0,N,F,C1, or Br) which substitutes at the boron site. No B-C bonds have been formed photochemically, even when, as in the CH3Br and the HFA reactions, methyl or perfluoromethyl radicals are present Also, no B-C bonded compounds were formed when borazine was photolyzed with benzene, pyridine, cyclopentadiene, allene, ketene, acetylene, or acetone. 

FIGURE 15.13 Orbital overlap in the reaction of a ketene with cyclopentadiene. S and L stand for small and large. 

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