Carbenes and Ketens

Cycloadditions of Carbenes and Ketens.—Carbenes in which the empty p-orbital is part of a Htickel aromatic system show nucleophilic properties and react with electron-poor alkenes. Diphenylcyclopropenylidene adds 1,4 to tetracyclone, giving, after CO loss, the spiro-system (315). The reaction of cycloheptatrienylidene is more complex. The initial adduct is not isolated but behaves as if it were (316) and loses CO to give an interconverting set of isomeric hydrocarbons which terminate in (317) and (318) in the ratio 1 2. The same set can be produced photochemically but not thermally from the spiro-hydrocarbon (319).  

Cyclopheptatrienylidene reacts with dicyanobicyclo[2,2,2]octatriene to give 8% of (320). Possible steps leading to the product include (a) the expected addition, (6) a thermal homo-1,3-carbon shift, and (c) a homo-1,4-addition. The final step (d) is considered to be a [ 2 + 2 -I- 2j] process and likely, because of good overlap of the three a-bonds and the relief of strain in the small rings. A process equivalent to step (c) above is postulated in the addition of difluorocarbene to norbornadiene, 

Reaction of norbornadiene with diphenylketen slowly gives the expected exo [2 -f- 2] 1 1 adduct, but in the presence of excess diene and after longer times a low yield of (324) is produced. Brief heating at 200 °C converts (324) into (325).Benzene reacts with 2-methoxyallyl bromide in the presence of NajCOg and AgOCOCFj at room temperature to yield 11 % of (326). This is believed to be a concerted cycloaddition of the 2-methoxyallyl cation.  

JefTord, nT. Kabengele, J. Kovacs, and U. Burger, Tetrahedron Letters, 1974, 257 Helv. Chim. Acta, 

Pyrolysis of the diacetate gives a 2.5 1 mixture of trans,trans- and cis,cis-diacetoxy-alkyl-butadienes. Pyrolysis of (331) at 450 °C gives (333), probably via (332). Contrary to a previous report, (333) is not formed from benzyne and cycloheptatriene. The ketone (334) has been made from (335) plus benzyne followed by ozonolysis. Pyrolysis of (334) gives (336) and (337).  

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Thermal reactions of N-aryl cyclopropenone imines 268 are differentiated by the nature of the N-aryl substituent. Imines 268 (Ar = phenyl, p-nitro-phenyl) undergo isomerization to N-aryl-2-phenyl-indenone imines 271 when heated in aprotic solvents202. Since in protic solvents, e.g. ethanol, only the iminoester 272 is isolated, evidence seems to be given for the intermediacy of 269 implying carbene and ketene imine functionality, which may either cause electrophilic ring closure with a phenyl group to form 271 or may add to the hydroxylic solvent (272). 

Heterocycles as precursors of carbenes and ketenes, including those with heterocyclic fragments, in gas phase 93SL9. 

Fig. 3. The diazoketone reagent used for affinity labeling, attached to the hapten dinitrophenylglycine. The reactions as carbene and ketene are shown [C. A. Converse and F. F. Richards, Biochemistry 8, 4431 (1969)].

Visser, P., Zuhse, R., Wong, M.W. and Wentrup, C. (1996) Reactivity of carbenes and ketenes in low-temperature matrices. Carbene CO trapping, Wolff rearrangement, and ketene-pyridine ylide (zwitterion) observation. Journal of the American Chemical Society, 118, 12598-12602. 

More definitive evidence for the formation of an oxirene intermediate or transition state was presented recently by Cormier 80TL2021), in an extension of his earlier work on diazo ketones 77TL2231). This approach was based on the realization that, in principle, the oxirene (87) could be generated from the diazo ketones (88) or (89) via the oxocarbenes 90 or 91) or from the alkyne (92 Scheme 91). If the carbenes (90) (from 88) and (91) (from 89) equilibrate through the oxirene (87), and if (87) is also the initial product of epoxidation of (92), then essentially the same mixture of products (hexenones and ketene-derived products) should be formed on decomposition of the diazo ketones and on oxidation of the alkyne this was the case. 

The actual product of the reaction is thus the ketene, which then reacts with water (15-3), an alcohol (15-5), or ammonia or an amine (15-8). Particularly stable ketenes (e.g., Ph2C=C=0) have been isolated and others have been trapped in other ways (e.g., as P-lactams, 16-64). The purpose of the catalyst is not well understood, though many suggestions have been made. This mechanism is strictly analogous to that of the Curtius rearrangement (18-14). Although the mechanism as shown above involves a free carbene and there is much evidence to support this, it is also possible that at least in some cases the two steps are concerted and a free carbene is absent. 

Nevertheless, a more traditional approach to the stabilization of carbenes and the investigation of their spectral properties deals with the direct generation of carbenes in low-temperature matrices, e.g. by the photolysis of diazo-compounds or ketenes. The method allows stabilization of carbenes in their ground electronic state, prevents intramolecular isomerization and also facilitates direct spectroscopic monitoring of their chemical transformations in low-temperature matrices. 

Additional evidence for a photochemically produced noncarbene precursor to ketene 29 is provided by product analysis. Photolysis of 25 in neat methanol leads to both carbene-derived (i.e., 30 in 75% absolute yield) and ketene-derived adducts (i.e., 31 in 18% absolute yield), but thermolysis of 25 in neat methanol (sealed tube at 170°C) provides only carbene-derived adduct 30 (91% absolute yield) The ratio... 

The photolytic Wolff ring contraction of diazopyridones (181) is a synthesis of pyrrole-2-carboxylic acids via carbene (182) and ketene (183) intermediates (76S754). 

Pyrolysis of Meldrum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione) 362 proceeds by loss of acetone and CO2 to give ketene. Because of the ready availability of the starting material and the ease with which it can be functionalized at the acidic 5-position, pyrolysis of Meldrum s acid derivatives has been widely studied. Pyrolysis of the 5-formyl and 5-acyl derivatives 363 gives formyl or acylketenes 364, which can be trapped in a number of ways170-171. in many cases, loss of acetone and CO2 is accompanied by loss of CO to give a carbene, and this is illustrated by FVP of 365 at 560 °C which affords the Q -diketone 368 by way of ketene 366 and carbene 367172. 

Schollkopf and co-workers have synthesized a number of cyclopropanone acetals by the addition of various sulfur- and oxygen-containing carbenes to ketene diethylacetals (Table 3).26>27> Similarly, cyclopropanone dithioacetals may be prepared by the addition of the Ws-thiomethyl and Ws-thiobenzylcarbenes 12a, b to olefins.29) However, cyclopropanone acetal formation by this method requires double bonds with considerable electron enrichment and the yields are generally low. With unsubstituted olefins such as cyclohexene, the carbenes 12 a, b tend to form dimeric and trimeric products such as 13 and 14, instead of the double bond addition products. 

Heterounsaturated monomers that undergo coordination polymerisation or copolymerisation with other monomers can be divided into two classes monomers with a carbene-like structure such as isocyanides and carbon monoxide which are coordinated by n complex formation with the transition metal atom at the catalyst active site, and monomers such as isocyanates, aldehydes, ketones and ketenes which are coordinated via 5-bond formation with the metal atom at the catalyst active site. 

The photolytic Wolff ring contraction of diazopyridones 247 leads to pyrrole-2-carboxylic acids 250 via carbene 248 and ketene 249 intermediates <1976S754>. The thermolysis of 2-azidopyridine A-oxides 251 affords A-hydroxy-2-cyano-pyrroles 252 (Scheme 137) <1973JOC173> (see also Section 3.4.3.11). 

In light of the above results it is interesting to note that the reaction of diphenylcyclo-propenone dimer spirolactone with ironenneacarbonyl yields a mixture of ring-opened vinyl carbene and -vinylketene complexes, and these interconvert under addition (or removal) of CO (equation 225) . A possible pathwav to vinylketene Fe-complexes, prepared earlier from cyclopropenes and ironcarbonyls " , may thus involve initial f -coordination, followed by ring cleavage to vinyl carbene and finally carbonylation to the ketene iron // -complexes. An analogous // -manganese complex is prepared similarly by the reaction of CpMn(CO),THF with 3,3-dimethylcyclopropene complex (equation 226) . ... 

As a final suggestion for future research, cyclobutanones have also provided the organic photochemist with the opportunity of investigating the existence of unusual and reactive intermediates oxacarbenes, trimethylene biradicals, trimethylenemethane biradicals, acyl alkyl biradicals, and ketenes. Evidence for the intervention of oxacarbenes in the ring-expansion reaction is quite compelling however, their unusual behavior relative to "typical" carbenes (e.g., failure to form cyclopropane adducts with some olefinic substrates) makes them prime subjects for further study and characterization. Unlike oxacarbenes, the existence of acyl alkyl biradicals (e.g., [30]) is tenuous at best. Ideally,... 

In contrast to the carbene and carbenoid chemistry of simple diazoacetic esters, that of a-silyl-a-diazoacetic esters has not yet been developed systematically [1]. Irradiation of ethyl diazo(trimethylsilyl)acetate in an alcohol affords products derived from 0-H insertion of the carbene intermediate, Wolff rearrangement, and carbene- silene rearrangement [2]. In contrast, photolysis of ethyl diazo(pentamethyldisilanyl)acetate in an inert solvent yields exclusively a ketene derived from a carbene->silene->ketene rearrangement [3], Photochemically generated ethoxycarbonyltrimethyl-silylcarbene cyclopropanates alkenes and undergoes insertion into aliphatic C-H bonds [4]. Copper-catalyzed and photochemically induced cyclopropenation of an alkyne with methyl diazo(trimethylsilyl)acetate has also been reported [5]. 

The ester group in II is suggestive—although it is not a proof—of the intermediacy of a ketene, and ketene production in diazocarbonyl chemistry usually implies a Wolff rearrangement. The construction of a three-carbon chain on the other side of the ketone is a confirmation of this prediction. In turn, the Wolff rearrangement requires an a-keto carbene precursor that is the fate of diazo compounds exposed to ultraviolet light (wavelength lower than 3200 A). All this is translated into the mechanism depicted in Scheme 43.1. 

In a related reaction, addition of chloro-, chloromethyl-, chlorophenyl or chlorofluoro-carbene to ketene alkylsilyl acetals and subsequent ring-opening (MeOH-NEt3 reflux) leads to the corresponding 2-substituted-2-alkenoic esters in high yields (equation 66) ... 

The migratory aptitude of R in (11) varies widely with its structure (see Section 3.9.2.1), the shift of an alkoxy group being among the slowest. The formation of alkoxyketenes in the photolysis of alkyl diazoacetates is a fairly recent discovery. The major competing reactions of the carbene precursor are insertions into the C—H and O—H bonds of alcohols employed as solvents and ketene traps. The extent of Wolff rearrangement varies with structure ethyl diazoacetate (20-25%), phenyl diazoacetate (45-60%), and A -methyldiazoacetamide (30%). These reactions are of limited synthetic interest at present. 

Light can be used to promote the Wolff rearrangement, too, and in this case the reaction is called the photo-Wolff rearrangement. The photo-Wolff rearrangement is probably a nonconcerted reaction. First, N2 leaves to give a free carbene, and then the 1,2-alkyl shift occurs to give the ketene. 

Photolysis of hydroxy Fischer carbene complexes (96) (Scheme 20) in the presence of alcohols under several atmospheres of carbon monoxide gives low to moderate yields of a-hydoxy esters (97). It is proposed that the reactions proceed via ketenes formed from the liberated or complexed carbenes and CO. In some cases, acetals formed via thermal decomposition of the carbenes are the major products. Photolysis of iron porphyrin carbene complexes results in cleavage of the iron-carbon double bond, producing a four coordinate iron(II) porphyrin and the free carbene. The carbenes can be trapped in high yield with a variety of alkenes. 

The cyclopropanols 13 were separated from the ketone by column chromatography and rearranged to eucarvone. In a closely related process, the addition of chloro(methyl)carbene to ketene alkyl silyl acetals afforded adducts 14 which were transformed without isolation into esters of 2-methyl-substituted a,/i-unsaturated acids 15. ... 

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