Elimination—addition ketene-forming

Treated with a base, l-(arylacetyl)benzotriazoles 954 eliminate benzotriazole to form ketenes 955. When no other reagent is added, ketene 955 is acylated by another molecule of 954 to produce ot-ketoketene 956 which upon addition of water and decarboxylation during the work-up is converted to symmetrical dibenzyl ketone 957... 

On prolonged reaction with aryl isocyanates, the pyrido [ 1,2-a]pyrimidines (262) give pyrido[l,2-a]-s-triazines (266) in poor yield.328 The suggested pathway is the addition of the aryl isocyanate to form the 3,3-disubstituted product (263), which eliminates the ketene (265) the residual part of the molecule (264) reacts with an additional mol of aryl isocyanate to give 266. The ketene (265) forms the quinoline (267), by ring closure, which gives 268 by aryl isocyanate addition. The quinoline (267 R = CH2Ph, X = H) could be isolated. 

Arylpropionicacids such as ibuprofen 105 are important NS AIs (non-steroidal anti-inflammatories). Only one enantiomer is active and some are administered as enantiomerically pure compounds through there is a problem with racemisation in the body by enolisation. This can be turned to advantage in deracemisation . Weak bases are enough to convert the acid chloride 106 into an enolate that eliminates 107 to form the achiral ketene 108. Addition of, say, ethanol then gives racemic esters 109 R = Et of ibuprofen. 

In many cases, a protonated molecular ion (M - - H)+ is the only ion observed in a thermospray spectrum but if ammonium acetate buffer is used, depending upon the relative proton affinities of the species present, an ammonium adduct (M - - NH4)+ may be the predominant ion. In addition, clusters may be formed with components of the mobile phase. Although the thermospray ionization process involves less energy than conventional Cl, and very little intense fragmentation is usually observed, the presence of ions due to the elimination of small molecules, e.g. water, methanol and ketene, is not unknown. These latter ions are usually of relatively low intensity when compared to the protonated or... 

In the alkoxycarbonylation, the hydride mechanism initiates through the olefin insertion into a Pd - H bond, followed by the insertion of CO into the resulting Pd-alkyl bond with formation of an acyl intermediate, which undergoes nucleophilic attack of the alkanol to give the ester and the Pd - H+ species, which initiates the next catalytic cycle [35,40,57,118]. Alternatively, it has been proposed that a ketene intermediate forms from the acyl complex via /3-hydride elimination, followed by rapid addition of the alcohol [119]. In principle the alkyl intermediate may form also by protonation of the olefin coordinated to a Pd(0) complex [120,121]. 

In this cyclodecarbonylation reaction, a ketene species is unlikely to be the reaction intermediate as added alcohols produce no esters. As shown in Scheme 6.26, the ruthenium acyl species 72 is likely to be the intermediate [25], which is prone to decarbonylationto give ruthena-cyclohexadiene 73 this species undergoes subsequent reductive elimination to form 2H-indene. Addition of proton or Ru to species 74 generated the benzylic cation 75, which after a 1,2-aryl shift gave the observed products. 

Another more efficient catalytic version of the reaction consists of the interaction of ketones with chiral amines [6] to form enolate-like intermediates that are able to react with electrophilic imines. It has been postulated that this reaction takes place via the catalytic cycle depicted in Scheme 33. The chiral amine (130) attacks the sp-hybridized carbon atom of ketene (2) to yield intermediate (131). The Mannich-like reaction between (131) and the imine (2) yields the intermediate (132), whose intramolecular addition-elimination reaction yields the (5-lactam (1) and regenerates the catalyst (130). In spite of the practical interest in this reaction, little work on its mechanism has been reported [104, 105]. Thus, Lectka et al. have performed several MM and B3LYP/6-31G calculations on structures such as (131a-c) in order to ascertain the nature of the intermediates and the origins of the stereocontrol (Scheme 33). According to their results, conformations like those depicted in Scheme 33 for intermediates (131) account for the chiral induction observed in the final cycloadducts. 

In the reaction of allyl acetate 217 with ketene silyl acetal 218 of methyl acetate, using a Pd catalyst coordinated to DPPP, cyclopropane 220 is formed in addition to the expected allylacetate 219 [104], The cyclopropanation becomes main reaction when TMEDA, as a ligand, and thallium acetate are added [105]. The cyclopropanation can be understood by the attack of the enolate ion at the central carbon of 7r-allylpalladium to form the palladacyclobutane 221, followed by reductive elimination. 

I. Kikkawa and T. Yorifuji, Synthesis, 1980, 877 as an alternative mechanism, the ester may be deprotonated, followed by elimination to form the ketene, addition of the second equivalent of reagent results in the formation of the ketone enolate. 

The ratio of spirohexan-4-one/spirohexan-5-one was close to 1 1 which can be rationalized by assuming a diradical mechanism as proposed for the cycloaddition of dimethylketene to methylenecyclopropane. Dichloroketene also underwent nonregioselective addition to methylenecyclopropane (49% yield) however, 4,4-dichlorospiro[2.3]hexan-5-one was formed as the main product. When methylenecyclopropane was reacted with chloro(2,2,2-tri-chloroethyl)ketene, generated by elimination of chlorine from 2,2,4,4,4-pentachlorobutanoyl chloride with zinc and phosphoryl chloride, 4-chloro-4-(2,2,2-trichloroethyl)spiro[2.3]hexan-5-one (10) was isolated in 31% yield. The isolation of a single isomer instead of mixtures as described above is possibly due to the different reaction conditions which do not guarantee an uncatalyzed cycloaddition. 

When ketene reacts with the formamidine (256), the final products are l,3-thiazin-6-ones (257), as in previous reactions of this type (see Section 6.07.8.2.1), and it may be assumed that the initial adducts (258) eliminate dimethylamine under the reaction conditions (Scheme 48). Unfortunately, the products are contaminated by derivatives formed by multiple additions of ketene <86PS327>. 

There are other possibilities besides a T.L, such as acylium ion formation, ketene formation, and direct displacement analogous to an Sn2 reaction (Figure 10.16). Such mechanisms are viable under certain conditions. Acylium ions are formed with acid halides, esters, and some amides under highly acidic conditions, and acid halides can form ketenes with base catalysis. However, by far the most common pathway is addition-elimination via a tetrahedral intermediate. Let s examine the evidence for this intermediate. 

Vinylketone easily reacts with Fe2(CO)9 to afford an oxadiene 7r-complex in high yield as shown in Scheme 15.6. The 7r-complex reacts with an alkyllithium under nitrogen atmosphere to afford 1,4-diketone. However, under a carbon monoxide atmosphere vinylketene is obtained as shown in Scheme 15.6 [79,80]. The formation of the 1,4-diketone, as shown in Scheme 15.7 [80], is at first the alkylanion to the carbonyl carbon with the addition of alkyllithium to form iron carbene, and the metathesis of the iron carbene with C = C proceeds. On the other hand, under a carbon monoxide atmosphere, the metathesis of the iron carbene with C = O proceeds, the alkyl group of alkyllithium is eliminated as a carboxylic acid to form an iron carbene, and reacts with carbon monoxide to afford a vinyl ketene as shown in Scheme 15.7 [80]. 

In the reaction of ketene with diazomethane, cyclopropanone is initially formed, which reacts with another equivalent of diazomethane to give cyclobutanone ". Diazoketones react with ketenes by addition to the diazo compound. The cycloadduct eliminates nitrogen to produce butenolides. However, the ketocarbene 370, generated from... 

Among alkali metal enolates, those derived from ketones are the most robust one they are stable in etheric solutions at 0 C. The formation of aldehyde enolates by deprotonation is difficult because of the very fast occurring aldol addition. Whereas LDA has been reported to be definitely unsuitable for the generation preformed aldehyde enolates [15], potassium amide in Hquid ammonia, potassium hydride in THE, and super active lithium hydride seem to be appropriate bases forthe metallation of aldehydes [16]. In general, preformed alkali metal enolates of aldehydes did not find wide application in stereoselective synthesis. Ester enolates are very frequently used, although they are more capricious than ketone enolates. They have to be formed fast and quantitatively, because otherwise a Claisen condensation readily occurs between enolate and ester. A complication with ester enolates originates from their inherent tendency to form ketene under elimination... 

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