Chloro ketene

A convenient method for the preparation of 2-methylenecyclobutanones is by use of trimethylsilylmethyl(chloro)ketene. The resulting eyclobutanones 23 can be readily dechloro-silylatcd to give the desired methyienecyclobutanones 24.129... 

For thermally induced [2 + 2] cycloadditions, the concerted mechanism is operative only in particular cases, such as in the reactions between an alkene or alkyne and a ketene. The ketene can be generated directly in the reaction mixture from the appropriate acid chloride with triethylamine. The cycloaddition reaction is stereospecific and occurs exclusively in a cis fashion. Although the intermolecular cycloaddition with ketene itself proceeds in poor yields due to the propensity of the unsubstituted ketene to undergo dimerization, it is quite an efficient reaction with ketenes containing electron-withdrawing substituents. Usually, a-chloro ketenes are employed as reagents formed in situ from the corresponding a-chloro acid chlorides. Typical examples are represented in the preparation of cycloadducts such as 378 and 379 (Scheme 2.127). The latter cycloadduct, prepared in modest yield (ca. 20%),... 

The nucleophile-induced reactions of 7-chtorobicyclo[3.2.0]hept-2-en-6-ones and related ketones have been thoroughly studied, mainly because these compounds are readily prepared by [24-2] cycloaddition of chloro ketenes to cyclopentadienes. ... 

Alkylideneaminopyrimidines added onto the jS-o-ribofuranosyl chloro-ketene 597 to give an adduct that eliminated a hydrogen chloride molecule to furnish, after de-O-protection, the pyrido[l,2-a]pyrimidin-3-yl C-nucleoside 598 (84MI3 85CPB2671) (Scheme 159). 

Halogenopyrimidines react with active methylene groups, such as those in diethyl malonate, ethyl cyanoacetate, ketene diethylacetal, etc. For example, 4-chloro-6-methyl-5-nitropyrimidin-2-amine (454) and dimethyl sodiomalonate give dimethyl 2-amino-6-methyl-5-nitropyrimidin-4-ylmalonate (455) (63ZOB3132) 2-chloro-4,6-... 

The lithium chloride-catalyzed addition of 2-phenylthiirane to diphenylketene may involve attack on carbon by chloride ion followed by addition of the anion of 2-chloro-l-phenylethanethiol to the ketene, but no data about the mechanism were given (69TL259). 

Whilst the addition of a chiral NHC to a ketene generates a chiral azolium enolate directly, a number of alternative strategies have been developed that allow asymmetric reactions to proceed via an enol or enolate intermediate. For example, Rovis and co-workers have shown that chiral azolium enolate species 225 can be generated from a,a-dihaloaldehydes 222, with enantioselective protonation and subsequent esterification generating a-chloroesters 224 in excellent ee (84-93% ee). Notably, in this process a bulky acidic phenol 223 is used as a buffer alongside an excess of an altemativephenoliccomponentto minimise productepimerisation (Scheme 12.48). An extension of this approach allows the synthesis of enantiomericaUy emiched a-chloro-amides (80% ee) [87]. 

The last [2 + 2] cycloaddition performed onto methylenecyclopropane itself consists of the use of ketene derivatives, particularly of dimethylketene 508 (Table 40, entry 1) [133]. The result is an almost equimolar mixture of the two possible regioisomers 511, albeit no yield has been reported. Anyway, the particular reactivity of methylenecyclopropane was confirmed, since it was found to be around 15 times more reactive than isobutene [133]. The scarce regioselectivity of this cycloaddition was confirmed by the reactions of the same ketene 508 with 2,2-disubstituted methylenecyclopropanes (entries 2 and 3) [134], BCP has also been shown to be reactive towards chloro-substituted ketenes 509 and 510, affording the expected cycloadducts 514 and 515 in mild conditions (entries 4 and 5) [13b],... 

The first synthesis of a cyclopropenone was reported in 1959 by Breslowls who achieved the preparation of diphenyl cyclopropenone (11) by reacting phenyl ketene dimethylacetal with benzal chloride/K-tert.-butoxide. The phenyl chloro carbene primarily generated adds to the electron-rich ketene acetal double bond to form the chlorocyclopropanone ketal 9, which undergoes 0-elimination of HC1 to diphenyl cyclopropenone ketal 10. Final hydrolysis yields 11 as a well-defined compound which is stable up to the melting point (120—121 °C). 

Meyers and Novachek described the Stille coupling of a chiral 2-bromooxazoline with a furylstannane to produce furyloxazoline [58]. Liebeskind and Wang conducted a benzannulation of a furylstannane using a Stille coupling with 4-chloro-2-cyclobutenone 62 to elaborate benzofuranol 63 via a dienyl ketene intermediate [59]. 

Matsuda et al. <1995H(41)2777> described an efficient synthesis of mesoionic [l,2,4]triazolo[4,3-A]pyridazines 390 and 391. The starting compound for the synthesis is the A-aminotriazole 389, which can be treated either with ethyl 2-chloro-3-ethoxyacrylate to yield 390 or with ketene dithioacetals to afford 391. The reactions proceed in good to high yield. 

This method has successfully been applied for the addition of chloro(l-chloro-2,2-dimethylvinyl)carbene — formed from 1,1,2-trichlo o-3,3-dimethylcyclopro-pane by dehydrochlorination and subsequent ring-opening — onto ketene methyl silyl acetals, the products of which are transformed to interesting allenic esters when treated with tetrabutylammonium fluoride [149]. 

Dichloroketene acts as a donor toward aromatic aldehyde [165], but chlorocyano-ketene behaves as an acceptor, as shown by the reactivity profile with a series of substituted benzaldehydes [97]. It must be remembered that chloro and cyano groups belong to different polarity categories, and although the fundamental donor/acceptor characters of the ketene unit do not change, the higher electrophilidty of the cyano-ketene reflects the acceptor influence by the cyano function. 

Ketene itself and simple alkylketenes are inert towards nonactivated alkenes. F or the preparation of cyclobutanones formally derived from ketene or an alkylketene and nonactivated alkenes, the more reactive dichloroketene or alkylchloroketenes can be used. The corresponding a,a-dichloro- or oc-chlorocyclobutanones can readily be dechlorinated by treatment with zinc in acetic acid, or tributyltin hydride in near quantitative yields. F or example cycloaddition of substituted cyclohexene to dichloroketene gave dichlorocyclobutanone 1 which was dechlorinated to 2 with zinc.13,18 Likewise cycloaddition of cycloalkcnes to chloro(methyl)ketene gave 3 which was dechlorinated to 4.14... 

Ketene reactivity in intramolecular cycloadditions parallel those in intermolecular reactions in which chloro-, vinyl-, aryl- and alkoxyketenes are more reactive than the alkylketenes. In most instances the ketene is generated by amine dehydrohalogenation of an acid chloride. There are, however, a few examples of ketenes prepared along less conventional routes as by the examples for the formation of 11.150 12,151 and 13.151... 

Silver(I) tetrafluoroborate converts a-bromo-substituted ketones, e.g. 7, to the corresponding fluoro-substituted ketones, e. g. 8, under anhydrous conditions.69 Attempts to convert the a-chloro-substituted ketenes under the same conditions failed.69... 

In continuation of the research on solid-phase synthesis of biologically interesting (3-lactam compounds towards the development of combinatorial libraries, Mata et al. [102] investigated use of 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) as a key reagent for the construction of the (3-lactam ring in a stereoselective manner. The popular explanation involves the reaction of ketene B with the imine to form a zwitterionic intermediate D (Scheme 13). Alternatively, it is the activated acid A that acylates the imine to form the zwitterion D by abstraction of proton with... 

An illustration of a cycloaddition reaction resulting in the formation of the N—C2 and C3—C4 bonds is the reaction of 2-chlorophenylketene (29) with dicyclohexylcarbodiimide, to give 3-chloro-l-cyclohexyl-4-cyclohexylimino-3-phenylazetidin-2-one (25) (Expt 8.10).17 The ketene is generated in situ from 2-chloro-2-phenylacetyl chloride by the action of triethylamine (cf. Expt 7.25). 

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

The Reformatsky reactions of methyl or ethyl bromoacetate with 4-acetoxy-,2,24 4-benzyloxy-,2 4-tetrahydropyranyloxy-,2 4-chloro-,8 and 4,4-dimethoxy-2-butanone1418 have been carried out. The adducts were converted to mevalonolactone by hydrolysis and, in the case of the acetal reactant, by appropriate reduction and oxidation procedures. The same Reformatsky-type syntheses of mevalonolactone have also been performed using the lithium and magnesium carbanions of acetate esters5,19 25 26 and the dianion of acetic acid28,27 instead of the usual zinc reagent. The intramolecular Reformatsky reaction of 4-(bromoacetoxy)-2-butanone gives mevalonolactone directly.28 A related route to mevalonolactone involves boron trifluoride-catalyzed cycloaddition of ketene to 4-acetoxy-2-butanone followed by hydrolysis.183... 

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