Radical reactions, domino processes

Masson and coworkers reported a-alkylation of imines through a three-component radical/cation domino process using bromomalonate 11, an enamide 13, and an alcohol as starting materials. First, an iridium species forms the alkyl radical 12 from 11 by single electron transfer (SET). Then enamide 13 reacts with 12 to produce the amidoalkyl radical 14. An oxidative radical-polar crossover reaction then furnishes an N-acyliminium cation 15, which finally reacts with nucleophilic alcohol to produce a-alkylated a-amido ether 16 (Scheme 5.5) [11]. 

For the reason of comparison and the development of new domino processes, we have created a classification of these transformations. As an obvious characteristic, we used the mechanism of the different bond-forming steps. In this classification, we differentiate between cationic, anionic, radical, pericyclic, photochemical, transition metal-catalyzed, oxidative or reductive, and enzymatic reactions. For this type... 

Besides the numerous examples of anionic/anionic processes, anionic/pericydic domino reactions have become increasingly important and present the second largest group of anionically induced sequences. In contrast, there are only a few examples of anionic/radical, anionic/transition metal-mediated, as well as anionic/re-ductive or anionic/oxidative domino reactions. Anionic/photochemically induced and anionic/enzyme-mediated domino sequences have not been found in the literature during the past few decades. It should be noted that, as a consequence of our definition, anionic/cationic domino processes are not listed, as already stated for cationic/anionic domino processes. Thus, these reactions would require an oxidative and reductive step, respectively, which would be discussed under oxidative or reductive processes. 

In an anionic/radical domino process an interim single-electron transfer (SET) from the intermediate of the first anionic reaction must occur. Thus, a radical is generated which can enter into subsequent reactions. Although a SET corresponds to a formal change of the oxidation state, the transformations will be treated as typical radical reactions. To date, only a few true anionic/radical domino transformations have been reported in the literature. However, some interesting examples of related one-pot procedures have been established where formation of the radical occurs after the anionic step by addition of TEMPO or Bu3SnH. A reason for the latter approach are the problems associated with the switch between anionic and radical reaction patterns, which often do not permit the presence of a radical generator until the initial anionic reaction step is finished. 

Instead of simply using two radical reactions in a domino process, the combination of three and more radical C-C- or C-N-bond forming radical transformations is also possible. This makes this methodology one of the most powerful procedures in the synthesis of complex molecules starting from simple substrates [77]. During the years, several strategies have been developed, and these are depicted in Scheme 3.50. The strategies can be classified as three types ... 

A dramatic improvement in this new round trip radical domino processes developed by Curran s group was presented by Takasu, Ihara and coworkers. The new method relies on the introduction of a conjugated ester moiety at the terminal olefm, thereby effecting an acceleration of the domino reaction accompanied with an enhancement of the regio- and stereoselectivity [81]. Thus, reaction of 3-196 with Bu3SnH led to a 4 3 mixture of the two diastereomeric tricycles 3-197 and 3-198 in 83% yield. In this process, the vinyl radical 3-199 is initially formed, but this smoothly cyclizes in 5-exo-trig manner to give radical 3-200 (Scheme 3.52). Due to... 

The connection of radical and pericyclic transformations in one and the same reaction sequence seems to be on the fringe within the field of domino processes. Here, we describe two examples, both of which are highly interesting from a mechanistic viewpoint. The first example addresses the synthesis of dihydroindene 3-326 by Parsons and coworkers, starting from the furan 3-321 (Scheme 3.79) [128]. Reaction of 3-321 with tributyltin hydride and AIBN in refluxing toluene led to the 1,3,5-hexatriene 3-324 via the radicals 3-322 and 3-323. 3-324 then underwent an elec-trocyclization to yield the hexadiene 3-325 which, under the reaction conditions, aromatized to afford 3-326 in 51 % yield. 

Abstract In this chapter different types of domino-processes are described which consist of the combination of cationic, anionic, radical, pericyclic and transition metal-catalyzed as well other reactions. The methodology is used for the highly effective synthesis of carbocycles and heterocycles as well as of natural products and other interesting materials. It is also employed as an efficient tool in combinatorial chemistry. 

In a combination of photochemical cyclization and a radical reaction Yoshimatsu et al synthesized 2-azabicyclo[33.0locta-3,7-diene 169 from the trienal hydrazone 166.1891 The domino process was initiated by irradiation of 166 at 400-500 nm in benzene. The transformation may include an intermolecular [2+2]-cyclization, followed by ring opening to give... 

Abstract Radical tandem reactions—and in a wider context radical dominos or cascades—have attracted a lot of attention because of their intrinsic elegance and the construction of a hroad and sometimes unique array of molecular architectiu es they allow in a single step. This review focuses on the latest progress in the design and development of new tandem reactions. The first part is devoted to intramolecular processes the second part covers tandem and domino processes involving both intra- and intermolecular steps. The third part introduces intermolecular-only reactions. Finally, the last part focuses on tandem reactions involving both radical and non-radical elementary steps. 

Tsuchii et al. reported a very interesting four-component domino process where an alkyne, two olefins and diphenyl diselenide sequentially react to form a highly functionalized cyclopentane derivative, after a linear addition sequence and 5-exo-trig cyclization [136]. This reaction can be seen as an interrupted polymerization process initiated by the addition of selenyl radical to an electron-deficient alkyne in the presence of a large excess of a Michael acceptor. The identity of each reaction partner is important for the outcome of the reaction. For instance, use of (PhS)2 instead of (PhSe)2 leads to the polymerization product rather than to the cyclization one, while (PhTe)2 did... 

Jang et al. reported a highly diastereoselective tandem radical reaction to prepare -polysubstituted homoallylic alcohols (Scheme 64) [175]. This new process relies on the initial addition of benzoyl radicals onto an olefin. The intermediate radicals such as 201 underwent a stereoselective vinylation (two elementary steps) to form the desired Bz-protected homoallylic alcohols in good yields. The stereochemical outcome of the reaction is strongly dependent on polar factors such as solvent polarity of Lewis acid additives. More sophisticated domino processes including cyclizations can be devised, as is the case for the formation of 203. 

Jahn et al. reported an elegant new domino process based on the combination of anionic and radical reactions relying on a key oxidation of anion 249 followed by a radical cyclization leading to 250 (Scheme 74) [207]. Radical 250 can be trapped by TEMPO to yield functionaUzed pyrrolidine 251 in high yield and acceptable stereoselectivity the 2-3 cis relationship was controlled in the initial anionic addition, but the relative configurations at C3 and C4 were largely non-controlled. All-carbon cyclopentanes [208], in particular prostanes [209] could also be prepared through this method. More recently, Jahn and Rudakov reported its extension to nitroalkenes [210]. 

Curran and coworkers [141] developed a palladium(0)-catalysed domino process for the synthesis of the very potent anticancer natural product (S)-camptothecin (283) [142] and its analogues (Scheme 8.70). Camptothecin (283) contains an ll//-indolizino[l,2- ]quinolin-9-one skeleton, which is also found in mappicine [143] and the promising new analogue DB-67 (287) [144]. A domino-radical reaction has been used for its construction in 40-60% yield [145]. However, the product is also accessible from the isonitrile 284... 

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