Iodine iodocyclization with

Attempted iodocyclization with iodine in moist acetonitrile of ethyl 2-hydroxypent-4-enoate (59) to give the iodotetrahydrofuran (62) gave instead a 2 1 mixture (80%) of syn- and -lactones (60) and (61). Labelling studies with H2 0 indicated that the probable mechanism of the reaction involved initial attack of the ester group upon the iodonium ion (63) to yield a mixture of epimeric carbocations (64), which upon attack by water would yield the orthoesters (65), elimination of ethanol from which giving the epimeric y-lactones (60, 61). ... 

Treatment of compound 22 with an excess of iodine in THF at 0 °C resulted in the formation of compound 23, the free hydroxyl group being favored in the nucleophilic attack to the iodonium ion. It is worth of note that, despite the presence of two double bonds, at 0 °C the reaction is regioselective. Increasing the temperature to 20 °C, the second iodocyclization with debenzylation occurs, affording compound 24 in 60% overall yield. 

D-Ribonolactone was converted into the allylic alcohol 227,104 whose condensation with PMB isothiocyanate followed by anti-Markovnikov iodocyclization with iodine afforded the iodo oxazolidinone 228 (82%) (Scheme 30).105 The latter was treated with a mixture of acetic anhydride and sulfuric acid, followed by activated zinc to... 

Attempted iodocyclization with iodine in moist acetonitrile of ethyl 2-hydroxypent-... 

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-... 

The iodocyclization of 2-methallylmercapto benzimidazole 247 proceeded in a regioselective manner by treatment with iodine and aqueous KOH in chloroform to give the dihydro-thiazolo[3,2- ]benzimidazole 248 (Equation 108) <1999RJO730>. 

Taguchi and colleagues189 studied the reactions of axially chiral maleimide and anilide derivatives 298 and 300 with cyclopentadiene (equation 83). The reaction of 298 with cyclopentadiene, catalyzed by diethylaluminum chloride, proceeded quantitatively with almost complete endo and diastereofacial selectivities to give 299 and 301, respectively. The reaction of 300 with cyclopentadiene was catalyzed by iodine and proceeded via a cationic iodocyclization intermediate. The reaction afforded a mixture of endo and exo isomers in a ratio of endo/exo = 97/3, the endo isomer being obtained with 97% de. 

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... 

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

In contrast, cyclizations of /V-alkoxy derivatives with iodine are much less selective (Table 30, entry 3), and similar results are observed with systems containing internal double bonds of either ( )- or (Z)-configuration.238 The stereoselectivity of the aminomercuration reaction of /V-methyl derivatives has been reported to be controlled by the choice of mercury(II) salt and solvent (entries 6 and 7).244 Cyclization with platinum salts showed little selectivity (entry 8).239 An iodocyclization of a complex N-alkyl system has been used in a recent synthesis of (+)-croomine.238... 

The reaction of the iodine-assisted addition can be carried out as an intramolecular process. The iodocyclizations of N-substituted dihydropyridines 313, 315 and 317 into corresponding polycyclic compounds 314,316 and 318 are described in [340] (Scheme 3.108). The heterocycles 318 can be further modified with... 

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. 

The iodocyclization of 2-substituted 4-pentenoic acids under kinetic conditions affords the dihydro-5-iodomethyl-2(3i/)-furanones with low 1,3-asymmetric induction19b. Thus, treatment of 2-methyl-4-pentenoic acid (1, R = CHS) with 1 equivalent of iodine in sodium hydrogen carbonate solution results in dihydro-5-iodomethyl-3-methyl-2(31/)-furanone (2, R = CH3) in 99% yield and cis/trans ratio of 68 32. The corresponding 3-methoxymethyl-7-lactone 1 (R = MOM) is obtained in 94% yield and 66 34 (cis/trans) diastereoselectivity. 

The iodocyclization of 4-methyl-5-hexenoic acid performed under conditions of thermodynamic control (iodine in acetonitrile in the absence of a base) leads to the preferential formation of the /raw.v-diequatorial 5-lactones (94 6) in 77% yield1. Similar results were observed starting from (S)-4-methyl-5-hexenoic acid (1), obtained from citronellol, with iodine in acetonitrile, followed by tributyltin hydride reduction. The 5,6-dimethylvalerolactone 2 was obtained in 40%) yield and 93.5 6.5 (irans/cis) diastereoselcctivity 2. 

The intramolecular iodocyclization of 3-penten-l-ols performed with iodine/sodium hydrogen carbonate in dry acetonitrile allows tetrahydrofurans to be obtained via a 5-endo-trig process. This method can result in obtaining 2,5-tram- or 2,5-m-tetrahydrofurans. depending on the geometry of the double bond127 - no. 

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. 

Disubstituted A-alkoxypyrrolidines were obtained by iodocyclization of 1-substituted 4-alkenyl-jV-alkoxyamines by the addition of iodine in acetonitrile in the presence of sodium hydrogen carbonate. Moderate 1,3-asymmetric induction was observed with little dependence on the bulk of the R1 substituent. The 2,5-/rc n.v-pyrrolidine trans-3 was the predominant product, unless the disubstituted double bond had E configuration77. The iodides were transformed to alcohols with net retention of configuration. 

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... 

After hydrolysis of the pentylidene, iodocyclization of the resulting diol under kinetic conditions produces the tetrahydrofuran 932 as a single diastereomer. Removal of iodine with tri- -butyltin hydride in the presence of a catalytic amount of triethylborane followed by reduction of the ester and reacetylation affords the key intermediate 935. Cleavage of the... 

N-Allylselenoureas react with iodine to afford 5-iodo-4//-5,6-dihydro-l,3-se lenazines 189 by iodocyclization (Equation 48) <2006CL626>. 

Further proof of the intermediacy of the iodohydrins 85 in the formation of the hydroxy-tetrahydrofurans 80 came from two sources. Firstly, treatment with potassium carbonate led to formation of the corresponding epoxides. Secondly, by providing a second alkene function, suitably positioned to trap the iodohydrin hydroxyl by a 6-eto-trig iodocyclization, we have been able to intercept these species and hence define a new approach to substituted pyrans. Thus, treatment of the dienyl hydroxy-ester 90 with iodine and NaHCO, resulted in the formation of pyrans 92 in the ratio of 3.2 1. Presumably, initial iodohydrin formation 91 is followed by a relatively non-stereoselective 6-exo cyclization. Further chemistry of such products has yet to be carried out, especially efforts to distinguish the two iodine atoms and to cyclize to give furopyran systems <01M1001>. 

Ishihara and co-workers [72] reported an iodocyclization reaction that produced polycyclic products (Scheme 13.35). These reactions were promoted by a stoichiometric amount of a chiral phosphoramidite and utilized iV-iodosuccinimide (NIS) as the iodine source. Although isomeric products were produced in the iodocyclization reaction, they could be converted to a single isomer upon treatment with chlor-osulfonic acid in 2-nitropropane. 

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