Ketene intermediate

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Ketenes absorb near 2100-2130cm . When the photolysis was carried out and the IR spectrum of the solution monitored, it was found that a band appeared at 2118 cm , grew, and then decreased as photolysis proceeded. The observation of this characteristic absorption constitutes good evidence for a ketene intermediate. As with UV-VIS spectroscopy, the amount of intermediate that can be detected depends both on the intensity of the absorption band and the presence of interfering bands. In general, IR spectroscopy requires somewhat higher concentration for detection than does UV-VIS spectroscopy. 

This finding suggests that some of the ester is formed via a ketene intermediate... 

Photolysis of a-diazoketones has also been used to prepare A-norsteroids. Results in the A-nor series support the ketene intermediate invoked for the assignment of the 16) -configuration to the D-nor acids. Thus, irradiation of 2-diazo-5a-cholestan-3-one (99) gives 2/ -carboxy-A-nor-cholestane (100, R = H) in 45 % yield. ... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

From a /3-keto ester ROH, toluene, reflux, 95% yield. The reaction in this case is proposed to proceed through a ketene intermediate. ... 

Evidence for the existence of a ketene intermediate was first obtained by Nakamura et al. (1972) in a study of the photolysis of 2,1-diazonaphthoquinone-5-sulfonic acid by flash photolysis in aqueous solution. An intermediate with a strong absorption at 350 nm and a lifetime of approximately 2 ms was found. 

The superior donor properties of amino groups over alkoxy substituents causes a higher electron density at the metal centre resulting in an increased M-CO bond strength in aminocarbene complexes. Therefore, the primary decarbo-nylation step requires harsher conditions moreover, the CO insertion generating the ketene intermediate cannot compete successfully with a direct electro-cyclisation of the alkyne insertion product, as shown in Scheme 9 for the formation of indenes. Due to that experience amino(aryl)carbene complexes are prone to undergo cyclopentannulation. If, however, the donor capacity of the aminocarbene ligand is reduced by N-acylation, benzannulation becomes feasible [22]. 

Alkoxycarbene complexes with unsaturation in the alkyl side chain rather than the alkoxy chain underwent similar intramolecular photoreactions (Eqs. 10 and 11) [60]. Cyclopropyl carbene complexes underwent a facile vinyl-cyclopropane rearrangement, presumably from the metal-bound ketene intermediate (Eqs. 12 and 13) [61]. A cycloheptatriene carbene complex underwent a related [6+2] cycloaddition (Eq. 14) [62]. 

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. 

Flash photolysis of benzoyl and naphthoyl diazomethane, which should exist in the s-cis conformation, led to ketene intermediates within the duration of the pulse ( 20 ns).241... 

Scheme 10.14 gives some other examples of Wolff rearrangement reactions. Entries 1 and 2 are reactions carried out under the classical silver ion catalysis conditions. Entry 3 is an example of a thermolysis. Entries 4 to 7 are ring contractions done under photolytic conditions. Entry 8, done using a silver catalyst, was a step in the synthesis of macbecin, an antitumor antibiotic. Entry 9, a step in the synthesis of a drug candidate, illustrates direct formation of an amide by trapping the ketene intermediate with an amine. 

Type I Cleavage Reactions Proceeding through Ketene Intermediates... 

The following reactions are believed to result from addition to ketene intermediates produced from type I cleavage reactions ... 

A ketene intermediate is also proposed in the following photolysis of the oxosteroid(38) ... 

Although the following examples involve ketene intermediates, no hydrogen transfer is necessary<40) ... 

Intramolecular interception of the ketene intermediate by an internal nucleophile (as available e.g. in the sulphimide 333 derived from 2-aminopyridine) gave rise to... 

Figure 5.29 pNPDP reacts with amine-containing compounds by its p-nitrophenyl ester group to form amide bonds. After photoactivation of the diazo derivative with UV light, a Wolff rearrangement occurs to a highly reactive ketene intermediate. This group can couple to nucleophiles such as amines. 

In 2001, Linder and Podlech studied the microwave-assisted decomposition of diazoketones derived from a-amino acids [340]. In the presence of imines, the initially formed ketene intermediates reacted spontaneously by [2+2] cydoaddition to form /3-lactams with a trans substitution pattern at positions C-3 and C-4 (Scheme 6.179) [340], In order to avoid the use of the high-boiling solvent 1,2-dichlorobenzene, most transformations were carried out in 1,2-dimethoxyethane under sealed-vessel conditions. Solvent-free protocols, in which the substrates were adsorbed onto an inorganic alumina support, led only to the corresponding homologated /3-amino acids. Evidently, traces of water present on the support trapped the intermediate ketene. 

These transesterifications are believed to proceed through the initial formation of a highly reactive a-oxo ketene intermediate, with the elimination of the alcohol component of the acetoacetic ester being the limiting factor. Subsequent trapping of the... 

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]. 

The concept of employing three components, all of which contribute one carbon atom to the final allene unit (see Scheme 5.4), is illustrated in its purest form by the reaction of carbon dioxide (165) with 2 equiv. of an alkylidenetriphenylphosphorane 166, the process very likely involving the generation in the first step of a ketene intermediate 167, which subsequently reacts with further 166 to yield the allene product 168 (Scheme 5.25) [66]. 

The nature of the reagent eventually providing the central carbon atom of the allene unit, the ylid and the ketene intermediate have been varied considerably over the years, as shown by the following selection of examples. 

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]. 

Ru(Tp)(PPh3)(CH3CN)2]PF6-catalyzed cydization of enynyl epoxides is shown to give various carbocyclic compounds depending on the types of epoxides a summary of the reaction protocol is provided in Scheme 6.22. Notably, these cyclized products are generated from dienyl ketene intermediate 59, which was trapped efficiently by alcohols to form the ester product. 

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... 

Photochemical or thermal extrusion of molecular nitrogen from ot-diazocarbonyl compounds generates a-carbonylcarbenes. These transient species possess a resonance contribution from a 1,3-dipolar (303, Scheme 8.74) or 1,3-diradical form, depending on their spin state. The three-atom moiety has been trapped in a [3 + 2] cycloaddition fashion, but this reaction is rare because of the predominance of a fast rearrangement of the ketocarbene into a ketene intermediate. There are a steadily increasing number of transition metal catalyzed reactions of diazocarbonyl compounds with carbon-carbon and carbon-heteroatom double bonds, that, instead of affording three-membered rings, furnish hve-membered heterocycles which... 

Azetidinones on a solid support 49 have been prepared in high yield by Staudinger reaction of a supported imine with an acid chloride in the presence of a base. The liberated p-lactams were of high purity <99TL1249>. Cycloaddition of a ketene intermediate, derived fi"om an azo compound, to an imine having an oxidatively cleavable chiral auxiliary N-substituent was used to obtain p-lactams 50. The trans. cis ratio which varied between 69 31 and 93 7, depended on the nature of the substituents R and R <99S650>. 

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). 

Carbene complexes undergo benzannulation under photochemical conditions with carbon monoxide to give the indolocarbazoles via a ketene intermediate, or aminobenzannulation with /t-butyl isonitrile under thermal conditions via a ketenimine (Equation (77) Table 3) <1997TL6787, 2001T5199>. 

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