Radical aryl migrations

Radical aryl migration reactions leading to formation of heterocycles 01T9649. 

Recently, it was shown that the radical aryl migration from silicon to carbon can be used for the preparation of biaryls [98]. Thus, transformation of bromide 64 under radical conditions, followed by desilylation, afforded biaryl 65 in 71% yield. The same product can be obtained by aryl migration from phosphorus (see 66) to the appropriate aryl radical [99]. To the best of our knowledge, this is the only report of a radical aryl migration between a phosphorus and a carbon atom. The... 

Aryl = Ph, 4-FPh, 4-MeOPh, 2-thienyl, 5-Me2N-naphthyl) Scheme 13. Radical aryl migrations from sulfur to carbon... 

In recent years, radical aryl migrations have received increased attention within the synthetic organic chemistry community. Yet, these reactions are also found as key steps in complex natural product synthesis [78]. For example, the neophyl rearrangement-which is the 1,2-phenyl migration of the neophyl radical 42 to form the tertiary radical 44 (probably via spirocyclohexadienyl radical 43)-was discovered by Urry and Kharasch more than 60 years ago (Scheme 13.9) [79], since which time numerous reports on neophyl-type rearrangements have been presented [80]. However, despite these efforts the postulated intermediate 43 has not yet been identified [81], The slow neophyl rearrangement (k = 762 s at 25 °C, [82]) can be used as a radical clock [83], The 1,2-aryl migration can also occur from C- to... 

Radical Migration. Mn(OAc)3 was used on traditional Ugi products to do a new radical cascade. Depending on the nature of the malonate substrates, either indanes (R = H) or 5-amidomalonates (R = Me) are obtained (eq 38). The products are obtained from a one-pot procedure involving an initial Ugi addition followed by treatment with Mn(OAc)3 and the malonate derivatives. A 1,4-radical aryl migration is the key step of the transformation. 

The more facile migration of aryl and other unsaturated groups involves bridged intermediates formed by an addition process. In the case of aryl migration, the intermediate is a cyclohexadienyl radical ... 

Aryl migrations are promoted by steric crowding in the initial radical site. This trend is illustrated by data from the thermal decomposition of a series of diacyl peroxides. The amount of product derived from rearrangement increases with the size and number of substituents ... 

The often potent biological properties of piperidine derivatives underlie their vast use in pharmaceuticals, agrochemicals, and natural products. It is for this reason that there exists a myriad of synthetic routes to variously functionalized and substituted piperidine derivatives, which will be highlighted in the subsequent section. In the past year there have been two reviews highlighting two approaches to the synthesis of piperidines. One review focused on the use of aziridines in parallel and solid-phase synthesis of substituted piperidine derivatives as well as other scaffolds <07EJO1717>. The other review covered the synthesis of 3-arylpiperidines by radical 1,4- and 1,2-aryl migration <07T7187>. 

Neopentyl and Neophyl Iodides. The halides mentioned above formed the corresponding organocobalt complexes on reaction with pentacyanocobaltate(II). While neopentyl radical is stable to rearrangement, the neophyl radical undergoes aryl migration (56) as follows ... 

In the 1,2-aryl migration (homobenzylic rearrangement) the delocalized spiro[2.5]octadienyl radical 26 is too short-lived for EPR detection, but has been identified by absorption spectroscopy. Many examples of this reaction are known,but products containing the cyclopropane ring are not obtained. 

Scheme 28. Aryl migration from tin to carbon-centered radical...

Later, Motherwell developed a new biaryl synthesis using 1,4- as well as 1,5-aryl migrations from sulfur to aryl radicals [101], Easily available arenesulfonates as well as arenesulfonamides were used as starting materials in these reactions 72). As in the Speckamp studies with primary alkyl radicals, the aryl radicals 71 were shown to also react by ortho attack to afford the side product 73. However, by judicious choice of the migrating aryl group, it is possible to completely suppress the ortho attack [102]. 

The aryl migration has been modeled computationally at the UB3PW91/G- ilG d,p) level. The bridged cyclohexadienyl radical is found to be a short-lived intermediate that is 10.1 kcal/mol above the open radical. The barrier for return to the open radical is 4.0 kcal/mol. The relative stability of the bridged radical is increased by most para-substituents, since they provide stabilization of the cyclohexadienyl radical. 

Radical reactions. In the presence of air (or oxygen), EtsB promotes radical formation. A tin-free cyclization of w-iodo carbonyl compounds is effected. Regioselective arylation can take advantage of 1,4-aryl migration from tin to a carbon radical center. a-Hydroxyalkylation at C-2 of THF is conveniently accomplished with RCHO. ... 

Figure 6.53. Isoflavone synthase (CYP93C) catalyzes the formation of isoflavone from 25 -flavone via an oxidative aryl migration. A possible mechanism involving an anchimerically stabilized radical is shown.

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