Diphenylketenes 4+2 cycloaddition reactions

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. 

Several unusual cycloaddition reactions of 9 with unsaturated ketones should be mentioned in conclusion the heterocumulene generated photolytically from 7 undergoes [8 + 2]-cycloaddition with tropone to form 33 (40%) the structure of the product has been unequivocally established by X-ray structure analysis 22,23). Once again, the affinity of phosphorus for oxygen is manifested an entirely analogous cycloaddition reaction is known for diphenylketene 26). 

Diphenylketene undergoes 2 + 2- or 2 -E 4-cycloaddition reactions with various 1,3-diazabuta-1,3-dienes. The 2 - - 4-, 4 -E 2-, 6 -E 4- and 8 -E 2-cycloaddition reactions of heptafulvenes have been reviewed. ... 

Many cycloaddition reactions have been carried out with ketenes and thioketones. The products are thiolactones (52). Hexafluorothioacetone and diphenylketene, however, do not undergo cycloaddition even after prolonged heating at 100°C. Good results can be obtained when the more stable dimer of this fluorinated thioketone (53) is used. Anionic monomer 54 could be released by the action of potassium fluoride in an aprotic solvent. Two-step cycloaddition to diphenylketene yields ketone 55. 

A new and completely different methodology involving a cycloaddition reaction has been described. The reaction between diphenylketene, ferf-butylcyanoketene or dimethylketene with 2,4,6-trimethylbenzonitrile A-oxide gave the corresponding 5(4//)-oxazolones 107 in moderate yields (Scheme 7.30). 

Boedeker and Courault215 reacted Schiff bases (151) derived from 2-aminopyridine and aromatic aldehydes with diphenylketene. In benzene at room temperature 4-oxopyrido[l,2-a]pyrimidines (152) were obtained in a reversible [4 + 2] cycloaddition reaction, whereas upon boiling mesitylene, irreversible [2 + 2] cycloaddition yielded azetidinones (150). Previously Sakamoto et al.216 prepared the azetidinones (150) in boiling xylene. 

In contrast to strongly solvent-dependent [2- -2]cycloaddition reactions, which proceed through a 1,4-dipolar zwitterionic intermediate by a two-step mechanism or through a dipolar activated complex by a one-step mechanism cf. Section 5.3.2, and Eqs. (5-33) to (5-35) [92, 94-107], [2- -2]cycloadditions are also known that exhibit concerted, nearly synchronous bond formation without significant charge separation on activation in the transition state. An example is given in Eq. (5-47). Since the rate constant for this diphenylketene/styrene addition is practically independent of solvent polarity [140], it can be classed as concerted. 

The [2 + 2] cycloaddition reaction proceeds via an ionic linear intermediate, which can be intercepted when the reaction is carried out in liquid sulfur dioxide, for example, when diphenylketene is added to a solution of diisopropylcarbodiimide in sulfur dioxide at —78°C. On warming and evaporation of the sulfur dioxide a 90% yield of 1,1-dioxo-... 

The (4+2)-cycloaddition reactions are theoretically and experimentally well founded for electron-rich dienes. However, those reactions with electron-rich dienophiles are less investigated. An early application of the inverse type of (4+2)-cycloaddition to pyridazine synthesis, i.e., from electron-deficient azoalkenes and alkenes, was reported by Sommer in 1977, [Eq. (4)]. A mixture of regioisomeric products 22 and 23 was obtained.107 108 However, in the presence of diphenylketene, products of either (2 + 2)- and/or (4+2)-cycloaddition (i.e., pyridazines) are formed arylazoalkenes thus behave similarly to a,/ -unsaturated carbonyl compounds in cycloadditions.109 2-Phenylazo-l-alkenes dimerize (a (4+2)-cycloaddition) in the absence of solvent to give pyridazines, or they may react with dienophiles.110-115 Some other cycloadditions of this type are reported.116-120... 

Benzoyl-2//-l,3-thiazines (144) and diphenylketene enter into [2 + 2] cycloaddition reactions via the imine bond, thereby providing access to thiazolo-)S-lactams (145) <85CS239>. Chloroketenes (from chloroacetyl chlorides and a tertiary amine) react in a similar manner and give chloro derivatives (146) (Scheme 27) <85BSB149>. With 6//-l,3-thiazines (147) the products are the corresponding -lactams (148) (Equation (17)) <86CJC597>. 

The (2 + 2)-cycloaddition reactions of ketenes with heterocycles via an endocyclic imino group have contributed substantially to the synthesis of penicillin (92a) and cephalosporin C (93a) antibiotics and structurally related heterobicyclic /Mactams.7 11 Reactions with relatively stable ketenes, e.g., diphenylketene, have been reported as well as reactions of heterocycles with mixtures of acid chlorides and tertiary amines. 

Roberts et al. in the early 90s reported that 1,3-cyclohexadiene derivatives such as 24 and diphenylketene undergo [2 + 2] and [4 + 2] cycloaddition reactions simultaneously to afford mixtures of adducts 25 and 26 (Scheme 11) (1992JCS(P1)1617, 1990JCS(P1)2613). Notably, in the case of R = H, the ratio is 56 44, whereas R = F afforded the [4 + 2] cycloadduct as the major product (1990JCS(P1)2613). Heating of the [4 + 2] cycloadduct causes partial isomerization to afford the [2 + 2] cycloadduct, indicating that the [4 + 2] cycloadduct is a kinetic product while [2 + 2] adduct is thermodynamically more stable (1992JCS(P1)1617). 

Dichloroketene can be reacted with N,N-disubstituted 2-aminomethy-lene-cyclopentanones 101a, -cyclohexanones 101b, -cycloheptanones 101c, and -cyclooctanones lOld to afford the 1,4-cycloaddition products, N,N-disubstituted 3,3-dichloro-4-amino-5,6-poly-methylene-3,4-dihydro-u-pyrones 102 (Scheme 34) (1972JHC1071). Diphenylketene and ketene also can undergo this 1,4-cycloaddition reaction (1967MFC1518). 

PROBLEM 20.46 In 1907, Staudinger reported the reaction of diphenylketene (1) and benzylideneaniline (2) to give [i-lactam 3. Although this reaction is formally a 2 + 2 cycloaddition reaction, there is ample experimental evidence to surest that the reaction is not concerted, but is instead a two-step process involving a dipolar intermediate. 

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. ... 

The general nature of these reactions was first recognized by Staudinger and his coworkers in the reaction of ketenes with olefins. Huisgen and his coworkers demonstrated that the cycloaddition reaction of diphenylketene with vinyl ethers is stereospecific, indicating a concerted one-step mechanism. However, more otfen the [2+2] cycloaddition reactions proceed in a stepwise fashion. In recent examples it was demonstrated that the initial reaction of ketenes with several substrates produces adducts which are different from the isolated ones (see Chapter 4, Section 4.1.4.2) . Also switter ionic intermediates are detected by low temperature spectroscopy. For example, Machiguchi and coworkers have detected the formation of 1,4-switter ionic species as intermediates in the reaction of bis(trifluoromethyl)ketene with ethyl vinyl ether. 

Vinylketenes also undergo [2+2] cycloaddition reactions with ethoxyacetylene. Diphenylketenes with a substituent on one ring, such as 98 (X = Me, OMe), react with ethoxyacetylene by a [4+2] cycloaddition sequence to form norcaradiene derivatives 99, which rearrange to give azulenes 100... 

The [2+2] cycloaddition reaction of ketenes with olefins was already observed by Staudinger and his coworkers, who postulated the four-membered ring structure for the cycloadducts. The rate of reaction of ketenes with olefins is as follows diphenylketene > dimethylketene > butylethylketene > ketene. Because of its slow rate of dimerization butylethylketene is an especially useful reagent and its cycloaddition to slow reacting olefins can be forced by using elevated temperatures. 

The [2+2] cycloaddition reaction of dimethyl- and diphenylketene to tetramethylallene is another example of the addition of the ketene C=C bonds across the cumulative C=C... 

The [2+2] cycloaddition reaction of ketenes with vinyl ethers and thioethers also occurs very readily. Even allyl ethers undergo this reaction. The reaction of diphenylketene with vinyl ethers is stereospecific, indicating a concerted one-step process . Also, dimethylketene and -MeOCH=CHMe affords a cycloadduct in which the alkene stereochemistry is maintained In contrast, the [2+2] cycloadduct obtained fl om t-butylcyanoketene and CH2=CHOEt or CH2=CHOAc did not give a 100% stereoselectivity and linear products are often also obtained, indicating the formation of a switter ionic intermediate. The latter are detected in the reaction of bis(trifluoromethyl)ketene with ethyl vinyl ether (see the General Introduction ). The initial reaction occurs across the C=0 bond of the ketene, which rearranges via switter ionic intermediates to form the cyclobutanone reaction product . 

Across N=0 bonds The [2+2] cycloaddition reaction of ketenes with nitroso compounds affords the four-membered ring cycloadducts. For example, diphenylketene reacts with nitrosobenzene to give the cycloadduct 312. On heating of the cycloadduct, dissociation... 

Azo derivatives of some heterocycles also undergo the [2+2] cycloaddition reaction with diphenylketene, generated in situ, from azobenzil . ... 

Also, azodicarboxylates react with diphenylketene to form mixtures of the [2+2] cycloadducts 319 and 1 2 adducts formed in an initial [4+2] cycloaddition reaction, followed by another [2+2] cycloaddition across the generated G=N bond to give 320. ... 

From 3-dimethylamino-2,2-dimethylazirine and diphenylketene, the [3+2] cycloadduct, resulting from addition across the C=0 bond of the ketene, is obtained in 60 % yield In contrast, some substituted azirines 357 react with diphenylketene to give 5-pyrrolin-2-ones 358 via the [3+2] cycloaddition reaction... 

Ketenes also undergo [3+2] cycloaddition reactions with typical 1,3-dipoles, such as nitrones and nitrile oxides. For example, t-butylcyanide V-oxide reacts with diphenylketene... 

Thermolysis of the heterocycle 367 affords a thiocarbonyl ylide, which reacts with diphenylketene in a stereospecific [3+2] cycloaddition reaction to give the adducts 368... 

Diphenylketene also reacts with diphenyldiazomethane to form the [3+2] cycloadduct 369. In this reaction, the C=0 bond of the ketene participates in the cycloaddition reaction. 

When diazabutadienes are used as the diene component, either [2+2] or [4+2] cycloadducts are obtained with phenyl- or in some cases with diphenylketene. In this manner, six-membered ring heterocycles are readily obtained. In the reaction of diazadienes with = NMc2, elimination of dimethylamine occurs in the cycloaddition reaction. Some of the [4+2] cycloadducts 413 derived from diazabutadienes and phenylketene are listed in Table 4.13. 

The vinyl ketenimines 128 react as azadienes in [4+2] cycloaddition reactions. For example, reaction with isocyanates gives the cycloadducts 129 (38-54 %), with diaryl sulfides the cycloadducts 130 (29-33 %) and with diphenylketene the cycloadducts 131 (47-53 %) 5. 

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