Ketene 4+2 cycloaddition reactions

Although an intramolecular thermal [2 + 2] allene-ketene cycloaddition reaction was reported, the regioselectivity was moderate [55]. 

The regiochemistry of ketene iminium salt cycloadditions can also differ from ketene cycloadditions. Whereas reaction of styrene with a series of ketene iminium salts gave 3-phenyI-cyclobutanones7 (60-70% yield) similar to the regiochemistry of ketene cycloadditions, reaction with a series of acrylates and a,/J-unsaturated ketones gave cyclobutanones 5 with regiochemistry opposite to what would be expected from electrostatic considerations of ketene cycloadditions.s... 

The Staudinger ketene cycloaddition is the nonphotochemical [2 + 2] cycloaddition of a ketene and an imine to form a P-lactam. Related ketene cycloaddition reactions include the cycloaddition of a keten with an olefin to afford a cyclobutanone, with a carbonyl to give a P-lactone, and with carbodiimides to form 4-imino P-lactams. 

Potassium acetate has been used in combination with acetic anhydride to form mixed anhydrides (eq 41). This is a convenient method to prepare ketene intermediates, presumably by the elimination of the mixed anhydride, for intramolecular [2+2] ketene cycloaddition reactions (eq 42). ... 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Bis(tnfluoromethyl)-4,5-dihydrooxazin-6-ones [28] and their O-acetylated dcnvatives [96] are formed on treatment of acyl imines with acetyl chloride-hiethylamine at room temperature. The reaction was interpreted as a cycloaddition reaction involving a ketene [28] However, the periselectivity and regiochemistry of this reactwn-are not in agreement with results obtained from the reaction of... 

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

Asymmetric synthesis of 3-amino (3-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

Bicyclic ketone 13 is a pivotal intermediate in Corey s approach to the prostaglandins. Buried within 13 is the five-membered ring of PGF2a, albeit in an undeveloped form. It would appear that a particularly direct approach to the synthesis of 13 would involve a [4+2] cycloaddition reaction between substituted cyclopentadiene 15 and ketene. Unfortunately, however, ketene itself is not a suit-... 

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-... 

Thermal [2h-2] cycloaddition reactions of carbonyl compounds were catalyzed by a Lewis acid. The catalyst forms complexes with the carbonyl compounds and enhances the electron-accepting power. The reaction shifts from the delocalization band to the pseudoexcitation band. Catalyzed [2h-2] cycloaddition reactions were observed with acetylenic compounds [28] and ketenes [29-31]. 

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 2+2 cycloadditions of benzyne to cis- and trani-propenyl ether gave cis- and fran -benzocyclobntanes as the main products, respectively [ 117,118], Stereospecific [2+2] cycloaddition reactions were observed between the benzyne species generated by the halogen-Uthium exchange reaction of ort/io-haloaryl triflates and the ketene silyl acetals (Scheme 23) [119],... 

Ketenes have cnmnlative bonds and can undergo [2+2] cycloaddition reactions across C=C and C=0 bonds. Interestingly, most of the prodncts obtained are cyclobutanones rather than oxetanes. Thermal [2+2] cycloaddition reactions in the pseudoexcitation band occur between electron donors and acceptors. Alkenes are donors while ketenes are acceptors. In contrast to the experimental observations. 

Cycloaddition reactions of ketenes with alkenes have long been known to give cyclobutanones [123] and to proceed with retention of the configurations [124], The reactions were classified into the symmetry-allowed cycloaddition reactions... 

Scheme 25 Pseudoexcitation in the [2+2] cycloaddition reactions of ketenes with alkenes...

The psudoexcitation preferentially occurs in ketenes. The energy gap is smaller between and of ketenes than between n and it of alkenes. The orbital of ketene is raised in energy by the interaction with the n orbital on the carbonyl oxygen above n of alkenes. The orbital of ketenes is lower in energy than n of alkenes. The pseudoexcitation is preferred in ketenes and occurs through the interaction. The [2h-2] cycloaddition reactions take place across the C=C bond of ketenes rather than C=0 bond. 

Ketenes can undergo [2h-2] cycloaddition reactions across the C=0 bonds when substituents lower the energy. The lowering of raises the DA )... 

Scheme 26 [2+2] Cycloaddition reaction of a ketene across the C=0 bond...

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