Migration-nucleophilic attack-cyclization

Treatment of aryl-substituted alkenes with hypervalent iodine compounds can lead to the formation of phenyliodinated intermediates, which can be stabilized by the aryl substituent via the formation of phenonium ions. Subsequent nucleophilic attack might then lead to rearranged products. This behavior can be nicely seen by comparing the unsaturated carboxylic acids 78 in their reaction with (diacetoxyiodo)benzene 3. The substrate 78a without the phenyl substituent is cyclized to the phenyliodinated intermediate 79, which is then attacked by the acetate under the formation of lactone 81 [142]. Substrate 78b is, however, then stabilized by the formation of an intermediate phenonium ion 80 and attack by the acetate is accompanied by a 1,2-phenyl migration and 82 is generated, Scheme 35 [143]. 

The proposed reaction pathway to 251 (Scheme 41) starts by nucleophilic attack of the dianion of the ethyl thioglycolate I on l,2-diimidoyl-l,2-dichloroethane 250, affording an intermediate II. Two possible routes, A and B, have been hypothesized for the formation of intermediate IV, which by proton migration leads to reactive species V. The cyclization step with simultaneous elimination of lithiated ethyl acetate, followed by protonation, complete the reaction cycle to give product 251. 

Smith reported cyclization reactions via acyllithium derived from a dianion and CO, which involved an alkyl group migration (Eq. (5.33)) [35], They also reported a reaction similar to Eq. (5.33), but not involving alkyl migration (Eq. (5.34)) [36], The eyclization of Eqs. (5.33) and (5.34) may proceed via ke-tenes or, alternatively, through direct intramolecular nucleophilic attack of the acyllithium on the amide carbonyl. Details of the mechanism are not known. 

Most steroidal skeletons are generated via 6-eitdo-6-einio-5-exo cyclizations. Initiation can be attempted by employing a niethylcyclohexyl cation. After nucleophilic attack of the terminating double bond a nonstabilized carbenium ion is formed which can undergo [1,2] hydride and [1,2] methyl migrations and a cis-anti-trans skeleton is formed69. 

McCleland has reported that 3-phenylpropan-l-ol [125] and 3-(p-methyl-phenyl)propan-l-ol 99 [126] cyclize to chromans when oxidized by the radical anion SO4, generated by redox decomposition of S20 with Fe. The intermediate arene radical cation 100 is attacked by the nucleophilic hydroxy group. Whereas 1,6-cyclization yields 7-methylchroman 102, 1,5-cyclization with subsequent C-migration leads to the regioisomer 6-methylchroman 105. A dependence of the isomeric ratio and the combined yields to the pH value is determined. While 7-methylchroman 102 is the main product over a wide pH range, 6-methylchroman 105 is only formed at low pH. When the pH is lowered, the combined yields decrease due to the formation of an a-oxidized non-cyclized product. 

The addition of sulfur nucleophiles to alkynes is a less developed transformation. However, Yamamoto described the attack of the sulfur atom of aryl thioethers to afford benzothiophenes (equation 31). More recently, it has been showed that propargylic thioethers or thioacetals undergo migration to give carbenes that cyclize in hydroarylation processes and thiocarbamates that evolve by propargylic rearrangement. Thiosilanes can perform as both sulfur nucleophiles and silicon electrophiles in intramolecular reactions to afford benzothiophenes (equation 32). ... 

Mechanistically, this process is similar to the cyclization processess involving fluoroolefins 16 and 24. The reaction involves the attack of nitrogen on the electron-deficient C=N double bond of 44 with the migration of the double bond, followed by a ring closure step via intramolecular nucleophilic displacement of fluorine in the CF=N- unit by alkoxy anion. The formation of 45 containing two C=N double bonds is the result of HF abstraction by triethylamine (Fig. 10.19). 

As is the case with the [3 + 2] cycloaddition reactions with aldehydes, bulky silicon substituents are supposed to suppress the attack of a chloride and/or oxygen nucleophile to silicon (path a) and allow the silyl group to migrate to a positively charged /5-carbon possibly through 5-endo cyclization of siliranium ion intermediates to give five-membered products (Scheme 3-102). 

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