Reactions of Ketenes

2-Bisketenes (11) can decarboxylate and then ring close to give cyclopropenones 

Amination of ketene has been studied by ab initio methods.Reactions of ammonia, its dimer, and its (mono)hydrate with ketene have been calculated and compared with earlier smdies of ammonia (at lower levels of theory), of water, and of water dimer. In general, the results favour initial addition of ammonia to the C=0 bond (giving the enol amide), as against addition to the C=C bond (which gives the amide directly). Amide formation is compared with the corresponding hydration reaction where enol acid and acid are the alternative immediate products. Most of the reactions, 

Hydration of carbodiimide (HN=C=NH) is described under Mines below. 

Synthesis of / -lactams via transition metal promoted Staudinger [2-1-2] cycloaddition of a ketene and an imine has been reviewed (63 references).  

Staudinger reaction of ketene and imine gives )5-lactam, via [2-1-2] cycloaddition. Six-membered rings can potentially be formed using a second equivalent of ketene or of imine, via [2-I-2-I-2] processes. DFT has been used to probe annuloselectivity in forming such (N,0), (N,0,0) or (N,N,0) ring systems for a range of seven reactants with substituents which are EWG, EDG or bulky. 

The Staudinger synthesis is catalysed by NHCs (A -heterocyclic carbenes), via Ye s possible ketene-first or imine-first mechanisms. To test these alternatives, four zwitterionic NHC adducts have been prepared two using A -tosyl benzaldimine and two using diphenylketene. All four adducts had 1 1 stoichiometry and have been extensively characterized by H- and C-NMR, X-ray crystallography and catalytic tests. The imine-derived zwitterions proved poor catalysts, whereas those derived from diphenylketene replicated the free carbene catalysts, strongly supporting the ketene-first route. 

Gas-phase reaction of ketene and water to produce acetic acid - both uncatalysed and with catalysis by an additional water molecule - has been studied computationally the reaction is found to be likely to occur in high-temperature combustion of biomass, but is negligible under ambient atmospheric conditions.  

Hydration of ketene to give acetic acid has been studied under atmospheric conditions, over a range of humidities.  

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

This [3-1-2] cyclodimerization occurs in 98% yield at 40 °C in 30 min. While the alkynophilic nature of gold is well known, the reaction is noteworthy for one ynamide partner playing a nucleophilic role, and the other electrophilic.  

For more references to Ketenes, see section titled Other Oxidation Reactions . 

The energy surface linking ketene (7, several conformers), the corresponding oxazinium olate (8), and related imidoylketenes, oxo-ketenimines, and their cyclization products has been calculated.19 Whereas (8) ring opens easily at room temperature, (7) is not directly observable, as its energy is ca 10 kcalmol-1 above (8). Many of the reactions in this manifold are pseudopericyclic in nature. 

Enantio-enriched enol esters - potential precursors of enantiopure a-arylalkanoic acids - have been prepared by asymmetric coupling of ketenes with aldehydes, using a chiral ferrocene bearing a dimethylaminopyridine function.20 

Acetylketene (MeC0CH=C=0)—generated by flash photolysis—showed the following selectivities towards functional groups amines alcohols (primary secondary tertiary) aldehydes ketones.19 The results accord with the ah initio calculations, which suggest planar, pseudo-pericyclic transition states. An imidoylketene, PrN=C(Me)CH=C=0, was also generated and showed similar selectivities. 

Nucleophilic additions to mesitylphenylketene [Ph(Mes)C=C=0, Mes = 2,4,6-Me3C6H2] and the related vinyl cation, Ph(Mcs)C=d)Mcs, proceed as if the mesityl group was effectively smaller than the phenyl group.20 The effect is explained by calculations that show that the phenyl is coplanar with the carbon-carbon double bond, while the mesityl is twisted the in-plane nucleophilic attack prefers the mesityl side. 

The cycloaddition of formaldehyde and ketene has been studied by ab initio methods.22 A two-step zwitterionic mechanism is suggested for dichloromethane solvent, while the gas-phase reaction is concerted but asynchronous. 

A stereoselective Mukaiyama-type aldol reaction of bis(trimethylsilyl)ketene acetals produces silyl aldols with syn stereoselectivity, predominantly due to steric effects.23 

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The alkylphenylacetyi chloride 843 and benzoyl chloride undergo decarbo-nylative cross-condensation to give the enone 845 in the presence of EtiNf723]. The reaction is e.xplained by the insertion of the ketene 844 into the Pd-aryl bond and, 3-elimination. To support this mechanism, o, d-unsaturuted ketones are obtained by the reaction of ketenes with aroyl chlorides[724]. 

Chemical Properties. The chemistry of ketenes is dominated by the strongly electrophilic j/)-hybridi2ed carbon atom and alow energy lowest unoccupied molecular orbital (LUMO). Therefore, ketenes are especially prone to nucleophilic attack at Cl and to [2 + 2] cycloadditions. Less frequent reactions are the so-called ketene iasertion, a special case of addition to substances with strongly polarized or polarizable single bonds (37), and the addition of electrophiles at C2. For a review of addition reactions of ketenes see Reference 8. 

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). 

Uses. The lowest member of this class, ketene itself, is a powerful acetylating agent, reacting with compounds containing a labile hydrogen atom to give acetyl derivatives. This reaction is used only when the standard acetylation methods with acetic anhydride or acetyl chloride [75-36-5] do not work weU. Most of the ketene produced worldwide is used in the production of acetic anhydride. Acetic anhydride is prepared from the reaction of ketene and acetic acid. 

Other processes described in the Hterature for the production of malonates but which have not gained industrial importance are the reaction of ketene [463-51-4] with carbon monoxide in the presence of alkyl nitrite and a palladium salt as a catalyst (35) and the reaction of dichioromethane [75-09-2] with carbon monoxide in the presence of an alcohol, dicobalt octacarbonyl, and an imida2ole (36). 

Petoxycatboxyhc acids have been obtained from the hydrolysis of stable o2onides with catboxyhc acids, pethydtolysis of acyhinida2ohdes, reaction of ketenes with hydrogen peroxide, electrochemical oxidation of alcohols and catboxyhc acids, and oxidation of catboxyhc acids with oxygen in the presence of o2one (181). 

The first synthesis of sorbic acid was from crotonaldehyde [4170-30-3] and malonic acid [141-82-2] in pyridine in 32% yield (2,17,18)- The yield can be improved with the use of malonic acid salts (19). One of the first commercial methods involved the reaction of ketene and crotonaldehyde in the presence of boron trifluoride in ether at 0°C (20,21). A P-lactone (4) forms and then reacts with acid, giving a 70% yield. 

The reaction of ketene itself with tettaalkyl titanates followed by a ketone R R C=0 gives P-hydroxy-esters, R R C0HCH2C02R. Polyinsertion of ketene and aldehyde into the Ti—O bond leads to di-, tri-, and tetraesters, eg, H0CR R CH2C02CR R CH2C02R (200). 

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

The reaction of ketene with the enamine (113) is reported (88) to give l-morpholino-2-acetyl-l-cyclohexene i.e., the enamino ketone expected from acylation of (113). The pyrrolidine enamine (28), however, has been shown to react (73) with excess ketene to give the a-pyrone (124). On the... 

Analogously, the reactions of ketene aminals with ketene or dimethyl ketene gave y-amino-a-pyrones and the linear acylation products, respectively 422). 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

Nitroethene rmdergoes rapid cycloaddidon to l,3-dienes the subsequent Nef reacdon gives cyclohexenones, which are formally produced by the Diels-Alder reaction of ketene v/ith... 

The reaction of ketenes (usually formed from treatment of acid chlorides with tertiary amines) with imines is a classic way to form /J-lactams [17,18]. Although widely used, it suffers limitations in scope and efficiency, since free ketenes are... 

In a similar reaction of ketene with diethyl phosphite in the presence of boron fluoride etherate as catalyst, diethyl 1-acetoxyvinylphosphonate is formed [113] see Eq. (69) ... 

The reactions of ketenes with enamines are apparently not concerted but take place by the diionic mechanism Otto, P. Feiler, L.A. Huisgen, R. Angew. Chem. Int. Ed. Engl, 1968. 7, 737. 

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...

Neier and coworkers have shown that piperidine diones (e.g., 105) can be prepared stereoselectively using a cascade Diels-Alder/acylation reaction of ketene acetal 104 <96T(52)11643>. 

World Health Organization 10th Annual Report, 1981, pp. 62-63. World Health Organization 11th Annual Report, 1982, p. 61. Heller, J., Penhale, D. W. H., and Helwing, R. F., Preparation of poly(ortho esters) by the reaction of ketene acetals and polyols, J. Polym. Sci., Polym. Lett. Ed., 18, 82-83, 1980. 

Taggi AE, Hafez AM, Wack H, Young B, Ferraris D, Lectka T (2002) The development of the first catalyzed reaction of ketenes and imines catalytic, asymmetric synthesis of P-lactams. J Am Chem Soc 124 6626-6635... 

Zhang YR, He L, Wu X, Shao PL, Ye S (2008) Chiral N-heterocyclic carbene catalyzed Staudinger reaction of ketenes with imines highly enantioselective synthesis of W-Boc P-lactams. Org Lett 10 277-280... 

As discussed in Section 10.4 of Part A, concerted suprafacial [2tt + 2tt] cycloadditions are forbidden by orbital symmetry rules. Two types of [2 + 2] cycloadditions are of synthetic value addition reactions of ketenes and photochemical additions. The latter group includes reactions of alkenes, dienes, enones, and carbonyl compounds, and these additions are discussed in the sections that follow. 

Carbonylation of the manganese carbene complex (tj5-C5Hs) (CO)2Mn=CPh2 to an analogous ketene complex has been reported (107). Compound 76 is also formed directly in the reaction of ketene with 45 (39). 

They can be prepared by the thermolysis of 1,2,3-thiadiazoles or by reaction of ketenes with phosphorus pentasulfide.111-113... 

Diels-Alder reactions [31] and 1,3-dipolar cycloadditions [32, 33] have been performed by use of this methodology. For example, Diaz-Ortiz described the hetero-Diels-Alder and 1,3-dipolar cycloaddition reactions of ketene acetals. The reactions were improved and products were isolated directly from the crude reaction mixture without polymerization of the ketene acetals [34],... 

Bicyclo-y-butyrolactones.1 The reaction of ketenes with chiral vinyl sulfoxides to obtain optically pure -y-arylsulfanylbutyrolactones (12,177) can be extended to a synthesis of bicyclic butyrolactones. Thus the arylsulfanyl group of 1 undergoes... 

The quinine catalyzed reaction of ketene with chloral. 

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