Electrophilic iodocyclization

The [2,3- ]> [2,3- ]. and [i,Z-b] isomers of 2,3-disubstituted furopyridines can be obtained from alkynes and o-iodoacetoxypyridines by a palladium-catalyzed cross-coupling reaction followed by an electrophilic iodocyclization reaction or a palladium-catalyzed cyclization in the presence of CO, as illustrated in Scheme 32 for [2,3-3] and [3,2-3] derivatives. When the pyridine ring contains strongly electron-withdrawing substituents such as carboethoxy, the reaction proceeded smoothly with benzyloxyalkynylpyridines <20020L2409>. 

High yields of lf/-isochromenes result from the intramolecular oxycu-pration of aUenes and subsequent asymmetric addition of the in situ-generated allylcopper species to carbonyl compounds, with excellent enantioselectivity (Scheme 39) (13AGE7177).4-Iodo-l-nitromethyl-lf/-iso-chromenes are prepared by condensation of 2-alkynylbenzaldehydes with nitromethane followed by an electrophilic iodocyclization (13JOC10476). 

Verma et al. [62] observed a chemoselective behavior of iodine in diSeient solvents in the electrophilic iodocyclization of o-alkynyl aldehydes. o-Alkynyl aldehydes on reaction with in CH C with appropriate nucleophiles provided pyrano[4,3-6]quinolines 40 via the formation of cyclic iodonium intermediate 39. In case of using alcohols as a solvent as well as nucleophile, o-alkynyl esters 42 were obtained selectively in good to excellent yields via the formation of hypoio-dide intermediate 41. Subsequently, o-alkynyl esters 42 were converted into py-ranoquinolinones and isocoumarins by electrophilic iodocyclization. The developed oxidative esterification provides a novel access for the chemoselective synthesis of esters 43 from aldehydes without oxidizing primary alcohol present in the substrate (Scheme 10.28). 

Type of reaction C-I and C-C bond formation Reaction conditions Nitromethane, room temperature Synthetic strategy Electrophilic iodocyclization Catalyst/reagent lodine/NaHCOs... 

Keywords Propargylic aryl ethers, iodine, sodium bicarbonate, nitromethane, room temperature, electrophilic iodocyclization, 3,4-disubstituted 2//-benzopyrans... 

In 2007, Ishihara and co-workers reported on the enantiose-lective iodocyclization of polyprenoids, which resemble many bioactive natural products and bioactive compounds (Scheme 42.24). In their studies, a stoichiometric amount of the binol-based phosphoramidite 75 was used as the promoter. The authors proposed that the Lewis basic 75 could activate Af-iodosuccinimide (NIS) to generate an electrophilic iodine source. The electrophilic iodocyclization of the polyprenoid would lead to the tra/w-fused ring mixture, which was then treated with CISO3H in t-PrN02 to give the desired iodopolycycles. It was revealed that the solvent was also a key factor for this asymmetric cycUzation. Despite... 

Electrophilic iodine reagents are extensively employed in iodocyclization (see Section 4.2.1). Several salts of pyridine complexes with 1+ such as bis-(pyridinium)iodonium tetrafluoroborate and b/.s-(collidine)iodonium hexafluorophos-... 

Enhanced stereoselectivity has been found using IBr, which reacts at a lower temperature.81 (Compare Entries 6 and 7 in Scheme 4.4.) Other reagent systems that generate electrophilic iodine, such as KI + KHSOs,82 can be used for iodocyclization. 

Electrophilic iodine reagents have also been employed in iodocyclization. Several salts of pyridine complexes with I+ such as bis(pyiidinium)iodonium tetrafluoroborate and bis(collidine)iodonium hexafluorophosphate have proven especially effective.61 y-Hydroxy- and d-hydroxyalkcncs can be cyclized to tetrahydrofuran and tetrahydropyran derivatives, respectively, by positive halogen reagents.62 (see entries 6 and 8 in Scheme... 

The iodocyclization reaction of diethyl /3-allenic c/.a-dilluorophosphonates (13) using I2 or IC1 as the electrophile has been reported to produce six-membered a-difluoromethylenephostones (14) in moderate to good yields with high regioselectivi-ties under mild conditions.28... 

An expedient method for synthesis of 2,3-disubstituted 1-benzoselenophenes (91) by the electrophilic cyclization of various 1 -(1 -alkynyl)-2-(methylseleno)arenes (90) has been reported recently (Scheme 24). This method tolerates a wide of variety of functional groups, and proceeds under exceptionally mild reaction conditions [141], Moreover, an efficient solid phase synthesis of 91 based on a combination of palladium-mediated coupling and iodocyclization protocols has been developed [142],... 

Formation of a highly electrophilic iodonium species, transiently formed by treatment of an alkene with iodine, followed by intramolecular quenching with a nucleophile leads to iodocyclization. The use of iodine to form lactones has been elegantly developed. Bartlett and co-workers216 reported on what they described as thermodynamic versus kinetic control in the formation of lactones. Treatment of the alkenoic acid 158 (Scheme 46) with iodine in the presence of base afforded a preponderance of the kinetic product 159, whereas the same reaction in the absence of base afforded the thermodynamic product 160. This approach was used in the synthesis of serricorin. The idea of kinetic versus thermodynamic control of the reaction was first discussed in a paper by Bartlett and Myerson217 from 1978. It was reasoned that in the absence of base, thermodynamic control could be achieved in that a proton was available to allow equilibration to the most stable ester. In the absence of such a proton, for example by addition of base, this equilibration is not possible, and the kinetic product is favored. 

Electrophile-mediated cyclization reactions of alkynes tethered to pendant heteroatom nucleophiles is an emerging strategy for the synthesis of heterocycles. This methodology has now been applied to the synthesis of pyrroles. The iodocyclization of 3-aminoalkynes 1 led to the formation of dihydropyrrole 2 <07TL7906>. Treatment of the latter with mesyl chloride in the presence of triethylamine then gave (i-iodopyrrolcs 3. 

Furo[2,3-6]furans (e.g., 10) are obtained in good yield by iodocyclization of unsaturated lactols. The reaction is carried out with iodine and other related electrophilic reagents, such as iodine chloride or /V-iodosuccinimide, at low temperature. Diastereomeric mixtures are obtained and the stereoselection is moderate to good, isomer 10A being the major component of the mixture97. 

Two separate reports of electrophilic 5-endo-dig iodocyclization reactions of o-alkynylanilines leading to 3-iodoindoles were disclosed. Treatment of Sonogashira product 114 with iodine led to 3-iodoindole 115 <04TL539>. Similarly, treatment of Sonogashira product... 

Abstract The synthetic uses of molecular iodine are described. This chapter discusses the versatile uses of iodine in heterocyclic synthesis. Iodine is a universal oxidizing agent, a mild and nontoxic Lewis acid catalyst, and it catalyzes various organic reactions with high efficiency and selectivity. Also, iodine acts as an electrophile-nucleophile dual activator in the reactions. Further applications are the introduction of protecting groups, deprotection, iodocyclization, C-C bond formation, and formation of heterocycles. It is quite clear from the growing number... 

For the stereocontrolled formation of nonterminal vinyl iodides the iodocyclization of allenes proved to be very useful. When the trichloroacetimidate 638 was treated with iodine in the presence of base, the (Z)-vinyl isomer 639 was generated as the major product in a kinetically controlled electrophilic addition-cyclization sequence [242],... 

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