Wolff ketene reaction

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. 

The requisite a-diazo thiol esters are conveniently prepared by using the "detrifluoroacetylative" diazo transfer strategy previously developed in our laboratory. Cycloadditions are best carried out by using as little as 0.006 equiv of rhodium(II) acetate to promote the thia-Wolff rearrangement. Reactions involving the more nucleophilic ketenophiles proceed smoothly in refluxing dichloromethane (40°C), while cycloadditions with less reactive partners are best accomplished in 1,2-dichloroethane (83°C). As is standard for ketene cycloadditions, the optimal protocol involves slowly adding a solution of the diazo thiol ester to a solution of the ketenophile and catalyst in order to minimize competitive ketene dimerization. 

The rearrangement of acylcarbenes to ketenes is called the Wolff rearrangement (reaction 18-8). A few rearrangements in which carbenes rearrange to other carbenes are also known. ° Of course, the new carbene must stabilize itself in one of the ways we have mentioned. 

Phenylketene generated by photochemical Wolff rearrangement in the presence of an acid anhydride and an isocyanate gives a 3-component reaction forming acrylamides 194, in a process involving ketene reaction with the isocyanide and then acylation by the carboxylic add (Eqn (4.123)). ... 

The diazo ketone 3, when treated with silver oxide as catalyst, decomposes into ketocarbene 5 and dinitrogen Na. This decomposition reaction can also be achieved by heating or by irradiation with uv-light. The ketocarbene undergoes a Wolff rearrangement to give a ketene 6 ... 

There are several reactions that are conceptually related to carbene reactions but do not involve carbene, or even carbenoid, intermediates. Usually, these are reactions in which the generation of a carbene is circumvented by a concerted rearrangement process. Important examples of this type are the thermal and photochemical reactions of a-diazo ketones. When a-diazo ketones are decomposed thermally or photochemically, they usually rearrange to ketenes, in a reaction known as the Wolff rearrangement.232... 

Different rearrangements were observed in other cases. Thus, Maas22 reported that when photolyzed in benzene the polysilyldiazoketone 180 gave the isomeric ketene 181, the product of a Wolff rearrangement (a 1,2 carbon-to-carbon rearrangement) of the initially formed carbene 182 (Eq. 57). The isomeric bis-silylketene 183 was not observed, but the siloxa-tene 184 was also a product of the reaction. 

Wolff rearrangements were also observed when most of the same acylsi-lyldiazoalkanes were photolyzed in acetone instead of benzene.21 The ketenes 185 resulting from a 1,3-methyl migration of the silene were detected in addition to the expected ene product 186 derived from the reaction of the silene with acetone (or other enolizable ketones) (Eq. 58). When R = Ad, only the cyclic siloxatene 187 was formed under the same... 

Carboalkoxymethylenes, like acylmethylenes, undergo rearrangement to ketenes as well as the olefin addition and C—H insertion reactions characteristic of methylenes.<37> Thus the photolysis of ethyl diazoacetate in olefinic solvents leads to substantial yields of products, which can be rationalized in terms of a Wolff rearrangement of the carboethoxymethylene followed by cycloaddition of the resulting ethoxyketene to the olefin ... 

The overall reaction is reminiscent of the Wolff rearrangement of a-diazo carbonyl compounds which gives ketenes. Compounds 6 formally represent their phosphorus analogues and are sometimes also designated as phosphenes 11... 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

A similar synthesis of mechanistic interest rather than preparative value involves the thermal reaction of dimethyl 2,5-bisdiazo-3,4-diketoadipate (89, Scheme 23) with benzofuran (91)." The presumed intermediate is the pyrone cation 90 produced from the adipate 89 by the Wolff rearrangement, cyclization, and loss of nitrogen. Electrophilic substitution then affords the benzofuran 92, which can be isolated. Ring opening and cyclization of the resultant ketene 93 then affords the dibenzofuran 94 in poor (0.4%) yield. 

Scheme I. Photolysis of a diazonaphthoquinone (DNQ) positive-resist sensitizer. The reaction leads to a carbene (1), which undergoes a Wolff rearrangement to give a ketene (2). Finally, this ketene can react with water present in the resin to give an indenecarboxylic acid (ICA) (3).

---