Cyclization, radicals with dienes

The present volume contains 13 chapters written by experts from 11 countries, and treats topics that were not covered, or that are complementary to topics covered in Volume 1. They include chapters on mass spectra and NMR, two chapters on photochemistry complementing an earlier chapter on synthetic application of the photochemistry of dienes and polyenes. Two chapters deal with intermolecular cyclization and with cycloadditions, and complement a chapter in Volume 1 on intramolecular cyclization, while the chapter on reactions of dienes in water and hydrogen-bonding environments deals partially with cycloaddition in unusual media and complements the earlier chapter on reactions under pressure. The chapters on nucleophiliic and electrophilic additions complements the earlier chapter on radical addition. The chapter on reduction complements the earlier ones on oxidation. Chapters on organometallic complexes, synthetic applications and rearrangement of dienes and polyenes are additional topics discussed. 

In comparison to the cyclization reactions shown above, intermolecular Meerwein arylations are often more difficult to conduct. Since the aryl radical addition to the alkene is no longer favored by the close proximity of the reacting centers, the probability for a direct recombination of the aryl radical with scavengers Y is significantly increased (Scheme 17). To maintain the desired reaction course from 44 to 45 including steps (1) and (2) [89, 90], Meerwein arylations have for a long time mostly been conducted with activated alkenes, such as acrylates (R = COOR ), vinylketones (R = COR ), styrenes (R = Ph), or conjugated dienes [91,92]. These types of alkenes are known for fast addition of aryl radicals. 

A tandem radical 5-exo cyclization/radical addition/allylic substitution reaction was subsequently described [292]. Allylic ot-bromo acetal 242b cyclized cobalt-catalyzed. Addition to diene 245 and subsequent coupling with coformed organocobalt(I) species generates an allylcobalt complex, which undergoes reductive elimination to cyclic product 246 in 93% yield (cf. Fig. 56). 

Harrowven [33] has reported two methods for carrying out the radical cyclization reactions of dienes attached to a Wang polystyrene support. Treatment of solid-supported diene 195 with either thiophenol or p-tolylbenzeneselenosulfonate, in the presence of AIBN, triggers 5-exo-trig... 

As can be seen from the few examples cited above SET processes are now fairly common in organic photochemistry. One of the areas where considerable study has taken place is the process referred to as a photo-NOCAS. Within this framework Albini and coworkers have shown that the products formed from the reaction of 2,3-dimethylbut-2-ene with 1,4-dicyanobenzene are compounds (22)- 25). The reaction was brought about using phenanthrene as the initial light absorber. This technique leads to cleaner reactions than those where the 1,4-dicyanobenzene is irradiated directly. The solvent system used is methanol/ acetonitrile and products (24) and (25) are the result of solvent incorporation. A further example of photo-NOCAS chemistry has been reported by Arnold and coworkers.Typical of the examples studied is the reaction illustrated in Scheme 2. The cyclization of the dienes (26) was also examined. This specific example deals with the generation of radical cations from (/ )-(+)-a-terpineol and (/ )-(+)-limonene with 1,4-dicyanobenzene as the electron accepting sensitizer. In another detailed study on reactions of this type the factors that control the regiochemistry in photo-NOCAS processes have been assessed. ... 

There are many examples of such reactivity and some of these have been reviewed by Roth and coworkers, a research group that is extremely active in this area. An example that is typical of the processes encountered involves the cyclization of the diene geraniol (1). In this case the sensitizer is 9,10-dicyanoanthracene (DCA) and the reactions are carried out in methylene chloride. The authors state that a contact radical-ion parr is involved, i.e. the radical cation of the diene is in close proximity to the radical anion of the DCA. Reaction within this yields the cyclopentane derivatives 2 and 3 in the yields shown. The ring formation is the result of a five centre CC cyclization within the radical cation of 1. When a more powerful oxidant such as p-dicyanobenzene is used as the sensitizer in acetonitrile as solvent, separated radical-ion pairs are involved. This leads to intramolecular trapping and the formation of the bicyclic ethers 4 and 5 . The bicyclic ether incorporates an aryl group by reaction of the radical cation of the diene with the radical anion of the sensitizer (DCB). This type of reactivity is referred to later. Other naturally occurring compounds such as (/fj-f-bj-a-terpineol (6) and (R)-(- -)-limonene (7)... 

In a similar case, hydrosilylation of a 1,6-diene or 5-en-l-one with tris(trimethylsilyl)silane gives the cyclized products with a preferred as orientation of the alkyl groups7. The intermediate silylalkyl or siloxyalkyl radical, respectively, is trapped intramolecularly to give substituted cyclopentanes. 

A summary of rate data is given for the systematic study of the formation of cyclic compounds during thermal reactions of olefins or of olefins with butadiene. As a next step in order to investigate cyclization at pyrolysis conditions, the reactions of allyl radicals with olefins were studied kinetically. 1,5-Hexa-diene (diallyl) and diallyl oxalate (DAO) were employed as source... 

The geometry of the double bonds within the macrocycles may have a significance influence over the course of the transannular radical cyclizations. Compared with 121, the Z, -cycloundeca-4,8-dien-l-yne 128 gave the 6,7-bicy-clic 132 by 6-endo cyclization of the vinyl radical 130 (Scheme 20.33). " These examples of tandem transannular radical cyclization of cycloundeca-4,8-dien-l-ynes demonstrated its potential for synthesis of stereochemicaUy complex polycyclic compounds. They also showed the subtle influence of the structures of the substrates over the outcome of the reactions and pointed to the need for systematic investigation of these powerful transformations. 

The groups at the termini of the 1,4-pentadiene system also affect the efficiency and direction of the the di-7c-methane reaction. The general trend is that cyclization oceurs at the diene terminus that best stabilizes radical character. Thus, a terminus substituted with aryl groups will cyclize in preference to an unsubstituted or alkyl-substituted terminus ... 

When free radicals are added to 1,5- or 1,6-dienes, the initially formed radical (9) can add intramolecularly to the other bond, leading to a cyclic product (10). When the radical is generated from an precursor that gives vinyl radical 11, however, cyclization leads to 12, which is in equilibrium with cyclopropylcarbinyl radical 13 via a 5-exo-trig reaction. A 6-endo-trig reaction leads to 14, but unless there are perturbing substituent effects, however, cyclopropanation should be the major process. 

The first examples of a consecutive radical 5 -exo-/dig-5-exo-dig cyclization of 1,5-diynes have been accomplished by the same researchers [43]. These authors were able to show that their cycloisomerization procedure provides access to strained semicyclic, conjugated dienes with a functionalized dioxatriquinane framework which occurs in the aglycones of steroidal cardiac glycosides, such as isogenine (3-96) [44] and C-norcardanolide (3-97) (Scheme 3.24) [45]. 

The parent compound, 69, has been synthesized and characterised <2003ZFA1475>. 4-Chloro-hepta-l,6-diene was reacted with Mg. No Grignard rearrangement was noticed but instead the Grignard reagent was converted into l-allyl-3-butenylphosphonous dichloride by reaction with PC13. Reduction with LiAlH. produced l-allyl-3-butenyl-phosphane. Radical-initiated cyclization led to the product, l-phosphabicyclo[3.3.0]octane. Four derivatives were similarly prepared and characterized (70-73). Compound 74 was similarly prepared via a radical reaction < 1997PS(123)141 >. 

A new approach to piperidines via cyclization of dienes, such as 158, employs a phosphorus hydride mediated radical addition/cyclization reaction <06JOC3656>. This reaction proceeds with complete regioselectivity to create the 6-exo-trig product 159, although as an inseparable mixture of two of the four possible diastereomers. 

Free-radical chain reactions have been reviewed60. The cyclization of dienes by the action of free radicals is illustrated for the case of the 1,6-heptadiene derivative 90 (E = CC Me) in equation 56. Treatment with tosyl radicals, produced from tosyl chloride and a catalytic amount of dibenzoyl peroxide, generates the radicals 91, which cyclize to 92. The latter reacts with tosyl chloride to form 93 and tosyl radicals are regenerated. The product is obtained in 85% yield as a 6 1 mixture of cis- and fraws-isomers61. 

A new entry to exocyclic dienes was reported by Sha who uncovered that a radical cyclization of the vinyl iodide 100 can lead to the formation of an exocyclic dienes fused with a tetrahydrofuran ring. The cyclization is proposed to proceed in a 5-(n-exo)-exo-dig fashion <00OL2011>. 3,4-Disubstituted tetrahydrofurans can also be constructed via the cyclization of O-stannyl ketyls and allylic 0-stannyI ketyls onto electron-rich or electron-poor alkenes <00TL8941>. 

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