Ketene intermediate mechanism

In contrast to a-fluorination, direct a-chlorination and a-bromination were developed on the basis of ketene intermediate mechanism in the presence of O-benzoylquinine (122) by Lectka and coworkers in 2001 (Scheme 6.36) [64, 65], Ketenes derived from acid chlorides 120 with either BEMP resin or proton sponge are added to 122 to form zwitterionic enolates, which are a-halogenated by perha-loquinones 123, 124. Finally, O-benzoylquinine moiety is substituted by haloaro-matic phenolate anions, generated from 123 or 124, to afford chiral a-halocarbonyl products 121 up to 99% ee. 

This mechanism does not apply to unsubstituted or N,N-disubstituted aryl carbamates, which hydrolyze by the normal mechanisms. Carboxylic esters substituted in the a position by an electron-withdrawing group (e.g., CN or COOEt) can also hydrolyze by a similar mechanism involving a ketene intermediate. These elimination-addition mechanisms usually are referred to as ElcB mechanisms, because that is the name given to the elimination portion of the mechanism (p. 1308). 

The anhydride (72) gives quite different products, (73) and (74), with tris(dimethylamino)phosphine to those previously obtained with triethyl phosphite. The formation of (73) and (74) is suggested to involve keten intermediates and an alternative mechanism is proposed for the phosphite reaction. 

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]. 

Scheme 6.25 shows a plausible mechanism involving ruthenium vinylidene and ruthenium-stabilized ketene intermediates. The ketene intermediate was verified through efficient trapping of this spedes with isobutanol to produce esters [23]. Nucleophilic attack by epoxide oxygen at the Ca-carbon of ruthenium vinylidene produces the seven-membered ether spedes 64, which ultimately forms ruthenium... 

The authors propose a mechanism for the transformation which involves the formation of a ketene intermediate at elevated temperature. Cyclization involving the adjacent nitro group then yields the zwitterionic species 115 which decarboxylates to give carbene 116. Einally, this cyclizes to yield the products (Scheme 12). 

This reaction is particularly interesting because the starting compound has the trans, trans structure and the product must arise from a cis intermediate in order to form the ring. A possible isomerization mechanism involves a ketene intermediate. 

Finally, if the a-carbon of the acid moiety (i.e., the carbon bound to the carbonyl carbon) is substituted by an electron-withdrawing group that renders the a-hydrogens more acidic, the ester may hydrolyze by an elimination mechanism involving a ketene intermediate ... 

Hetero-Diels-Alder reaction of 44 with enol ether 13 as the dienophile gives cycloadduct 45, which is not isolable but reacts with the water formed in the condensation step with loss of acetone and C02 to lactone 15. A suggested mechanism for the formation of lactone 15 is a retro Diels-Alder reaction which leads to the ketene intermediate 46. Ketene 46 adds to the water formed in the previous condensation step, yielding /3-keto-carboxylic acid 47, which then undergoes decarboxylation to 48. 

The mechanism of the reaction is not known photoinduced CO loss and photoinduced CO-carbene coupling to yield a ketene intermediate were considered. 

The trimethylsilylynolate is prepared on treatment of trimethylsilyldiazomethane (23) with BuLi followed by exposure to carbon monoxide. The mechanism is explained by the fact that the lithiated silyldiazomethane (24) adds to carbon monoxide to give the labile a-diazoacyllithium 25, which rearranges to the ynolate 27 via the ketene intermediate 26 (equation 8). ... 

Tentative rationalizations of these stereochemical results have been offered on the basis of a mechanism involving a ketene intermediate reacting with an imine. However, it is by no means proven that all these reactions involve an intermediate ketene. Several pathways can lead from an acid chloride, an imine and triethylamine to a -lactam (Scheme 11). Thus the origin of the stereochemical selection in these multistep processes is not very well understood. 

The mechanism proposed by Ddtz involves the insertion of a carbon monoxide into the vinyl carbene complex intermediate with the formation of the vinyl ketene complex (255). Electrocyclic ring closure of (255) leads to the cyclohexadienone complex (252), which is related to the final tenzannulation product by a tautomerizadon when R is hydrogen. The mechanism proposed by Casey differs from that of Ddtz in that the order of the steps involving carbon monoxide insertion and cyclization to the aryl or alkenyl substiment is reversed. < Specifically, the vinyl carbene complex intermediate (248) first undergoes cyclization to the metallacyclohexadiene (249), followed by cartion monoxide insertion to give the intermediate (251), and finally reductive elimination to give cyclohexadienone intermediate (252). At this time the circumstantial evidence favors the intermediacy of vinyl ketene intermediates since they can be trapped from these reactions and isolated where the metal is dispaced from the vinyl ketene functionality however, there is not any evidence which can rule out the alternative mechanism. 

The reactions of both alkoxy and amino complexes are highly stereoselective and give the unnatural epimer at the C-6 position in the penicillin analogs, but methods are known for inversion at this center, llie mechanism of these reactions is thought to involve the intermediacy of a metal-4cetene complex whose formation is photo-induced.Early indications that this was the case came when it was found these reactions fail to give cyclic products of any kind under thermal conditions. More recently, vi-nylketene complexes have been trapped from these reactions.With the recent realization that metal-ketene intermediates are likely to be involved in these reactions further development of the photo-induced reactions of Fischer carbene complexes can be anticipated. 

Lynch JE, Riseman SM, Laswell WL, Volante RP, Smith GB, Shinkai I, Tschae DM. Mechanism of an acid chloride-imine reaction by low-temperature FT-IR beta-lactam formation occurs exclusively through a ketene intermediate. J. Org. Chem. 1989 54 3792-3796. 

Lynch, J. E. Riseman, S. M. Laswell, W. L. Tschaen, D. M. Volante, R. P. Smith, G. B. Shinkai, I., Mechanism of an Acid Chloride-Imine Reaction by Low-Temperature FT-IR P-Lactam Formation Occurs Exclusively through a Ketene Intermediate. / Org. Chem. 1989,54,3792. 

R.E Pratt and TC. Bruice, The Carbanion Mechanism (El b) of Ester Hydrolysis. III. Some Structure-Reactivity Studies and the Ketene Intermediate, J. Am. Chem. Soc., 1970, 92, 5956. 

Catalytic NBS, toluene, 90-100°C, 52-94% yield. It is likely that the reaction is actually HBr catalyzed. It is noteworthy that normal esters fail to react, which implicates a mechanism that may involve a ketene intermediate. 

Benzisoxazoles could be obtained by cyclization reactions forming N—O, O—C(7), or N—C(3) bonds as well as by heterocyclic rearrangements <84CHEC-I(6)l>. 1,2-Benzisoxazole (313) is synthesized from lithiated 3,5-dimethyl isoxazole (312) and a-oxoketene (311) (Equation (62)) <88TL50I>. Thermal transformations of ethyl nitrophenyl ethanoates (314) resulted in cyclization, to afford 2,1-benzisoxazole (316) via the ketene intermediate (315). Its mechanism has been discussed with evidence <95CC2457>. 

Figure 2 (a) X-ray crystal structure of MHPCO (2.1 A, PDB 3gmc). The monomer is shown with FAD and MHPC bound at the active site, (b) The active site of MHPCO. (c) Proposed mechanism for the oxidative ring-opening reaction catalyzed by MHPCO with flavin hydroperoxide (18) acting as an electrophile, (d) An alternative mechanism for the catalytic transformation through a ketene intermediate (23). 

Figure 7.8. The oxidation of terminal acetylenes, and even some internal acetylenes, results in the formation of ketene intermediates that react with water to give the carboxylic acids (see Chapter 6). It appears that the ketenes also react with active-site residues, inactivating the P450 enzyme that forms them. The hydrogen that undergoes a 1,2-migration during the oxidation reaction is indicated by a star. The structures of 2-ethynylnaphthalene and 10-undecynoic acid, both of which inactivate P450 enzymes, at least in part by this mechanism, are shown.

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