Radicals, acyl reaction with alkenes

Alkyl, alkenyl, aryl and acyl radicals can all be used in cyclization reactions. Acyl radicals can be generated by addition of alkyl radicals to carbon monoxide, or more conveniently from acyl selenides, and undergo a variety of radical reactions. A synthesis of the sesquiterpene (—)-kamausallene made use of the radical cyclization from the acyl selenide 69 (4.61). Tris(trimethylsilyl)silane and triethylborane in air were used to promote the reaction, which is highly selective (32 1) in favour of the cis stereoisomer 70, as expected from a chair-tike transition state. Best yields in the cyclization reactions of acyl radicals are found with electron-deficient alkenes, indicating the nucleophilic character of acyl radicals. 

Acyl radicals can be generated and they cyclize in the usual manner. A polyene-cyclization reaction generated four rings, initiating the sequence by treatment of a phenylseleno ester with Bu3SnH/AIBN to form the acyl radical, which added to the first alkene unit. The newly formed carbon radical added to the next alkene, and so on. Acyl radicals generated firom Ts(R)NCOSePh derivatives cyclize to form lactams. ... 

Because the addition steps are generally fast and consequently exothermic chain steps, their transition states should occur early on the reaction coordinate and therefore resemble the starting alkene. This was recently confirmed by ab initio calculations for the attack at ethylene by methyl radicals and fluorene atoms. The relative stability of the adduct radicals therefore should have little influence on reacti-vity 2 ). The analysis of reactivity and regioselectivity for radical addition reactions, however, is even more complex, because polar effects seem to have an important influence. It has been known for some time that electronegative radicals X-prefer to react with ordinary alkenes while nucleophilic alkyl or acyl radicals rather attack electron deficient olefins e.g., cyano or carbonyl substituted olefins The best known example for this behavior is copolymerization This view was supported by different MO-calculation procedures and in particular by the successful FMO-treatment of the regioselectivity and relative reactivity of additions of radicals to a series of alkenes An excellent review of most of the more recent experimental data and their interpretation was published recently by Tedder and... 

Most synthetically useful radical addition reactions pair nucleophilic radicals with electron poor alkenes. In this pairing, the most important FMO interaction is that of the SOMO of the radical with the LUMO of the alkene.36 Thus, many radicals are nucleophilic (despite being electron deficient) because they have relatively high-lying SOMOs. Several important classes of nucleophilic radicals are shown in Scheme IS. These include heteroatom-substituted radicals, vinyl, aryl and acyl radicals, and most importantly, alkyl radicals. 

In designing multicomponent coupling reactions, the nature of the individual components is obviously a key factor. Generally speaking, carbon radical species, such as alkyl radicals, aryl radicals, vinyl radicals, and acyl radicals are all classified as nucleophilic radicals, which exhibit high reactivity toward electron-deficient alkenes [2]. To give readers some ideas about this, kinetic results on the addition of tert-butyl and pivaloyl radicals are shown in Scheme 6.2. These radicals add to acrylonitrile with rate constants of 2.4 x 106 M-1 s 1 and 5 x 105 M-1 s-1 at... 

Compound 31 forms an acylpyridinium species (32) by reaction with DMAP. Finally nucleophilic attack by the alcoholate on the acyl group of 32 generates ester 12 and regenerates catalyst DMAP. Since conjugated alkenes are sensitive toward radical reactions, TEMPO is added to the reaction mixture to inhibit radical side reactions. 

Cobalt complexes derived from Schiff bases 388 catalyzed the hydroxyacylation of electron-deficient alkenes (Fig. 90) [431, 432]. Thus, methyl acrylate 387 reacted with aliphatic aldehydes 386 in the presence of 5 mol% of the in situ generated catalyst, molecular oxygen, and acetic anhydride to 2-acyloxy-4-oxoesters 389 in 56-77% yield. When acetic anhydride was omitted, the yields of products were lower and mixtures of the free hydroxy compounds and acylated compounds resulting from Tishchenko reactions were obtained. Electron-rich alkenes did not undergo the transformation, since the addition of the acyl radical is much slower. The acylcobalt species inserts oxygen instead and acts as an epoxidation catalyst. 

Generation of 3-indolylacyl radicals from the selenoesters 149, using either /j-Bu3SnH or tris(trimethylsilyl)silane (TTMSS) followed by reaction with various alkenes, offers a route to 3-acylindoles 150. On the other hand, the use of n-Bu Sn2 under irradiation gave cyclopent[6]indole derivatives such as 151 via a cascade involving initial addition of the acyl radical to the alkene, and a subsequent oxidative cyclization at the indole C-2 <02JOC6268>. 

Acyl radicals are very useful synthetic intermediates. Their preparation is not simple since the corresponding halides are highly electrophilic and cannot be used as radical precursors. Organocobalt compounds were proposed as suitable source of acyl radicals [44]. However, the use of acyl selenides proved to be more general [45, 46]. These radical precursors can be efficiently prepared from the corresponding carboxylic acids and esters [47]. Acyl phenyl selenides should be preferred, when possible, relative to acyl methyl selenides due to the consumption of two equivalents of tin hydride with this last system (Scheme 1) [4]. Acyl selenides have found many applications in tandem radical additions to alkenes. Examples of intermole-cular [Eq. (18)] [48,49] and intramolecular reactions [Eq. (19)] [50a] are reported. The enoyl selenide 68 give the unsaturated acyl radicals 69. This intermediate... 

Roger and Mathvink reported on the extensive synthesis of ketones based on the acyl transfer reaction of acyl selenides to alkenes using tin hydride as the radical mediator (Scheme 4-24) [46]. A radical arising from the addition of an acyl radical to alkenes abstracts hydrogen from the tin hydride with the liberation of a tin radical, thus creating a chain. The addition process is in competition with de-carbonylation. In this regard, aroyl, vinylacyl, and primary alkylacyl radicals are most suitable for this reaction and secondary and tertiary acyl radicals are inferior. 

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