Kolbe-type synthesis

In the past few years, however, very efficient new methods of cyclisation proceeding via radical intermediates have been developed and several reviews [19a] and a comprehensive book by Giese [19b] have been published. Rather than reactions involving the dimerisation of two radicals -as in the Kolbe electrochemical synthesis [20] or the radical induced dehydrodimerisation developed by Viehe [21]-more important are the reactions between a radical with a non-radical species. The advantage of this type of reaction is that the radical character is not destroyed during the reaction and a chain-reaction may be induced by working with catalytic amounts of a radical initiator. However, in order to be successful two conditions must be met i) The selectivities of the radicals involved in the chain-reaction must differ from each other, and ii) the reaction between radicals and non-radicals must be faster than radical combination reactions. 

Tommasi et al. recently reported the carboxylation of l,3-dialkyHmidazoHum-2-carboxylates, which can be seen as a remarkable variant of the Kolbe-Schmitt synthesis [27]. In this case, it was shown that l,3-dialkyBmidazolium-2-carboxylates could be synthesized from 1,3-diaIkylimidazolium chlorides and C02 via a Kolbe-Schmitt-type reaction (actually, this was more of a Marasse variant, run in solution). The starting compounds were carboxylated in anhydrous dimeth-ylformamide (DMF) under approximately 5 MPa C02, at temperatures ranging from 353 to 408 K and with Na2C03/C02 as a catalyst, according to Scheme 5.4. 

Thermodynamic analysis indicates that such reactions are on the whole unfavorable. Furthermore, the complexity and uncertainty of the mechanism by which such reactions may occur makes the choice of proper catalysts largely an empirical selection. However, it must not be overlooked that such reactions as the Kolbe-Schmitt synthesis of salicylic acid from dry sodium phenoxide and carbon dioxide represent processes, the success of which might point the direction to the solution of the problems attending the realization of the type reactions mentioned above. 

Electrolysis of carboxylates in the presence of olefins may afford the radical addition products [5]. Intramolecular radical addition may furnish a simple and straightforward access to cyclic compounds. Mixed decarboxylative coupling of 6-alkenoic acids and various carboxylic acids giving cyclic compounds is utilized for synthesis of useful chemicals. For instance, a stereoselective synthesis of prostaglandin precursors is achieved successfully by mixed Kolbe-type decarboxylation [b](Fig.2). 

Some A -enecarboxylic acids undergo a rapid intramolecular cyclization reaction of the 5-exo-trig type prior to the radical coupling step. Substituted tetrahydro-furans [95] and pyrrolidines [96] can be prepared by this Kolbe route. It is preferable to protect the amine function in the pyrrolidine synthesis by N-formy ation in... 

Kolbe conditions to give 914. Reduction with lithium aluminum hydride, acetonide formation (acetone, PTSA), and Collins oxidation furnishes aldehyde 915. A Homer—Emmons-type condensation of 915 with dienyl phosphonate 916 affords triene 917 in 50% yield. A Diels-Alder cycloaddition of 917 with L-phenylalanine-derived pyrrolone 918 (xylene, 170 °C, 4 days) produces a separable 4 1 mixture of 919 and the undesired regioisomer. Introduction of the methanol functionality and elaboration of the terminal isopropylidene group to a ra 5-a,j -unsaturated system completes the synthesis (Scheme 135) [203]. 

Free-radical reactions may be divided into two classes. In the first, the product results from the combination of two radicals, as in the Kolbe synthesis. Electrolysis of the alkali metal salts of aliphatic carboxyhc acids results in the Hberation of alkyl radicals at the anode and their subsequent dimerization (Scheme 4.46). In the second class, the product results from the reaction of a radical with a molecule, as in the case of photochemical chlorination of methane. The fundamental difference between the two types of reaction is that the latter class involves a chain reaction. 

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