Carbenes, from ketenes

Photosantonic Acid. The formation of photosantonic acid (Formula 30) from lumisantonin poses problems of special interest. The ketene-carbene mechanism (Formulas 36-38) previously proposed (26,27) to account for this transformation fails to account for the formation of phenols in the irradiation of umbellulone (Formula 39) and the bicyclic... 

This brief article, which because of its limited size does not refer to all the work which has been done in the field, is intended to convince the reader that the photolytic generation of electron-rich ketene equivalents from Fischer carbene complexes represents quite a general and highly valuable synthetic methodology. One should expect that there will be a lot of interesting and useful applications arising from this chemistry in the future. 

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]. 

Irradiation of alkoxycarbene complexes in the presence of aUcenes and carbon monoxide produces cyclobutanones. A variety of inter- and intramolecular [2 + 2]cycloadditions have been reported. The regioselectivity is comparable with those obtained in reactions of ketenes generated from carboxylic acid derivatives. Cyclobutanones can be obtained with a high degree of diastereoselectivity upon reaction of alkoxy carbenes with chiral A-vinyloxazolidinones. For example, photolysis of (19) in the presence of (20) gives cyclobutanone (21) (Scheme 31). In addition to aUcoxycarbenes, carbenes having a thioether or pyrrole substituent can also be employed. Related intramolecular cycloadditions of y,5-unsaturated chromimn carbenes afford bicyclo[2.1. IJhexanones (Scheme 32). 

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 formation of the ketene derived from 12 has been reported to be complete within 10 ns following laser photolysis in aqueous solution [110b]. For a microsecond TRIR study of 12, see S. Oishi, Y. Watanabe, Y. Kuriyama, Chem. Lett. 1994, 2187. Picosecond transient absorption experiments have indicated that the carbene derived from 13 (R=H) has a lifetime of 20 ps in methanol however, the ketene growth rate could not be determined due to overlap with carbene absorption J.J.M, Vleggaar, A. H. Huizer, P. A. Kraakman, W. P. M. Nijssen, R. J. Visser, C. A. G. O., Varma, J. Am. Chem. Soc. 1994, 116, 11754. See also Ref. 110a. 

Carbenes from a-diazoketones have the special property that they rearrange faster than they are trapped. For example, rearrangement gives a ketene, which can be trapped by an alkene, and this forms the basis of a method for synthesizing four-membered rings (Scheme 5.59). A variant of this reaction is the ring contraction of carbenes from cychc a-diazoketones (Scheme 5.60). 

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). ... 

The photoaffinity labeling technique affords the opportunity to bypass the metabolic activation process for both mutagenesis and carcinogenesis by using photosensitive moieties to attach the drug to the biopolymer after initial binding has occurred in the dark. Nitrenes may be generated photolytically from azides, and carbenes from diazocompounds and ketenes. 

Vinyl ketenes derived from Fischer carbene complexes react with carbenoid reagents to give the [4+1] cycloadducts in high yields. For example, from the vinyl ketene 452 and Me3SiCH2N2, the cycloadduct 453 is obtained in 93 % yield... 

The role of diazocarbonyl precursor conformation has also been addressed recently by nanosecond TRIR methods with which the kinetics of the rearrangement process can be monitored directly. " When excited-state contributions are important, the ketene growth rate wiU be unresolvable on the nanosecond timescale (assuming a diazocarbonyl excited-state lifetime beyond the time resolution [50 ns] of the TRIR experiments performed). Thus, ketene production from only an excited state is indicated by a fast, unresolvable increase in ketene IR absorbance following laser photolysis. Production only from a relaxed carbene intermediate, on the other hand, would be revealed by a rate of ketene growth equal to that of carbene decay. For diazoester 19, the observed rate of ketene growth is equal to the rate of carbene decay, clearly demonstrating that ketene 20 arises entirely from carbene 21 (Scheme 7). 

Other Rea.ctions, The photolysis of ketenes results in carbenes. The polymeriza tion of ketenes has been reviewed (49). It can lead to polyesters and polyketones (50). The polymerization of higher ketenes results in polyacetals depending on catalysts and conditions. Catalysts such as sodium alkoxides (polyesters), aluminum tribromide (polyketones), and tertiary amines (polyacetals) are used. Polymers from R2C—C—O may be represented as foUows. 

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. 

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]. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

The main synthetic application of the Wolff rearrangement is for the one-carbon homologation of carboxylic acids.242 In this procedure, a diazomethyl ketone is synthesized from an acyl chloride. The rearrangement is then carried out in a nucleophilic solvent that traps the ketene to form a carboxylic acid (in water) or an ester (in alcohols). Silver oxide is often used as a catalyst, since it seems to promote the rearrangement over carbene formation.243... 

At the present, the most straightforward mechanism for the formation of J5 from 1 is via insertion of CO into the Th-C(acyl) bond to form a ketene (H, (eq. (4)) which subsequently dimerizes. Presumably, initial CO interaction could involve coordination either to the metal ion as shown or to the electrophilic vacant "carbene p atomic orbital. Considering the affinity of the Th(IV) ion for oxygenated ligands, interaction of the ketene oxygen atom with the metal ion seems reason-... 

Merlic demonstrated the direct, non-photochemical insertion of carbon monoxide from acylamino chromium carbene complexes 14 to afford a presumed chromium-complexed ketene 15 <00JA7398>. This presumed metal-complexed ketene leads to a munchnone 16 or munchnone complex which undergo dipolar cycloaddition with alkynes to yield the pyrroles 17 upon loss of carbon dioxide. 

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