Iodine mediation

Diels-Alder reaction of N-allylic enamides and lactam derivatives through iodine-mediated activation [98]... 

TABLE 5-1. Iodine-Mediated Asymmetric Diels-Alder Reaction of ( + )-44... 

A limited number of hypervalent iodine-mediated synthesis of thiophenes and benzothiophenes have been reported. An indirect approach for the synthesis of thiophenes involves formation of 1,4-butanediones [85JC-S(CC)420 87JCS(P1)559 88TL3703 89JOC2605], followed by treatment with phosphorus pentasulfide. This approach is especially useful for the synthesis of 3,2 5, 3"-terthiophene (134) starting from 1,4-diketone 65 (85SC789). 

Asymmetric synthesis of stavudine and cordycepin, anti-HIV agents, and several 3 -amino-3 -deoxy-P-nudeosides was achieved utilizing this cycloisomerization of 3-butynols to dihydrofuran derivatives [16]. For example, Mo(CO)6-TMNO-promoted cyclization of the optically active alkynyl alcohol 42, prepared utilizing Sharpless asymmetric epoxidation, afforded dihydrofuran 43 in good yield. Iodine-mediated introduction of a thymine moiety followed by dehydroiodination and hydrolysis of the pivaloate gave stavudine in only six steps starting from allyl alcohol (Scheme 5.13). 

Scheme 9 Iodine-Mediated Disulfide Formation on Solid Support 1071...

W/cm2. On the other hand, the, /sc delivered by the iodide/iodine-mediated cells continues to increase in almost linear fashion with the incident power. 

In addition to the procedures listed in Table 3.38, further reactions have been used to generate halides upon cleavage. In Section 3.5.2, iodolactonization is presented as a method for the preparation of iodomethyl lactones from resin-bound pentenoic or hexenoic acid derivatives. Closely related to the iodolactonization is the iodine-mediated formation of 2-(iodomethyl)tetrahydrofurans from resin-bound isoxazoli-dines (Entry 9, Table 3.38 for the mechanism, see Figure 15.5). Nitriles can also be prepared by cleavage and simultaneous dehydration of amides RCONH2 from the Rink or Sieber linkers with TFA anhydride (Entry 10, Table 3.38). 

An iodine-mediated 6(0) " -exo-Trig cyclization has been used in the synthesis of (25, 4/ )-4-hydroproline from (S)-O-benzylglycidol219. Stereocontrolled 5(0) " -endo-Trig iodoetherification has provided an entry to traw.s-2.5-disubstituted tetrahydrofuran derivatives220. On treatment with iodine, trichloroimidates of primary a-allenic alcohols are converted into oxazolines with high stereoselectivity221. 

Iodine-mediated removal of both prenyl protecting groups from aryl ether 506 leads to the unexpected formation of 3-(3-iodo-2,2-dimethylchroman-6-yl)propan-l-ol. The reaction proceeds via formation of the ortho-allylic phenol intermediate 507 by electrophilic removal of a prenyl species, followed by an iodine promoted electrophilic cycliza-tion (Scheme 111) <2001SL1989, 2002T5689>. 

A selenium dioxide induced oxidative cyclization of the 2 -hydroxychalcone 745 is a key step in the total synthesis of ( )-5 -methoxyhydnocarin-D (Scheme 189) <2005T4149>. DMSO containing catalytic amounts of iodine also effectively promotes the oxidative cyclization of 2 -hydroxychalcones to afford flavones <1996CHEC-II>. The DMSO-iodine mediated cyclization of the bis(2 -hydroxychalcone) 746 is a key step in the synthesis of the natural atropisomer4 4 ",7,7 -tetra-O-methylcupressuflavone (Equation 298) <1997TL1087>. Likewise, silica gel supported indium(in) halides catalyze the oxidative cyclization of 2 -hydroxychalcones to afford flavones in excellent yield (Equation 299) <2005TL253>. 

Scheme 8. Hypervalent iodine-mediated phenyl methyl ether oxidative coupling.

Scheme 38. Polymer-supported hypervalent iodine-mediated oxidative cyclization of a maritidine precursor.

Clauson-Kaas) are perhaps the most utilized methods for the de novo synthesis of pyrroles. Recent advances include the following novel approaches to 1,4-diketones Stetter addition of aldehydes to chalcones <07SC1109> ruthenium-catalyzed isomerization of 1,4-alkynediols <07TL5115> and Zn/iodine-mediated dimerization of a-bromoketones <07TL7215>. 

Relative to the initiator/activator mechanism shown in Scheme 5, it is interesting to compare vinyl ether polymerizations initiated with the HI/I2 system and with iodine alone. The former system provides living polymers of controlled molecular weights and very narrow MWD [58], whereas the latter has been known for more than a century but fails to give such controlled polymerizations (cf., Sections IV.A) [49,55]. In the iodine-mediated polymerization, iodine serves as both the initiator and activator one molecule of iodine first slowly adds across the vinyl ether double bond to give an adduct. The a-carbon-iodine bond is activated by another molecule of iodine [34,95]. Thus, both systems would in fact form the identical growing chain end [ CH2CH(OR)+.I3 ], and the ob-... 

Although isolated in small amounts, the pyridinium salts 282 (arising from the iodine-mediated oxidation of DHPs 281) do not afford benzimidazolium salts 279 in the presence of isocyanides. A likely pathway may start with the iodo-dihy-dropyridinium intermediate 280, which can be formed by interaction of iodine with the reactive double bond of the DHPs (Scheme 44). The isocyanide may subsequently attack these species to generate the nitrilium ion T, which interacts with a second equivalent of isocyanide to form cation U. This intermediate undergoes an intramolecular trapping by the enamine unit to close the bicyclic system V... 

The Schmitz reaction can be unsuccessful in sterically demanding environments in such circumstances, the electrophilic aminating agent reacts faster with ammonia than with hindered ketones <1965JA2665>. Consequently, the synthesis of 2-azi-camphane 64, a compound which is unobtainable under standard conditions <1996TL6647>, was achieved by slow diaziridination of camphor imine hydrochloride 63 (rather than camphor itself) with hydroxylamine-O-sulfonic acid (HOSA)-ammonia, followed by iodine-mediated oxidation (Scheme 22) <2001S379>. 

E22b, Section 6.1.1.2.1)j l Por stepwise regioselective disulfide formation, the iodine-mediated oxidative deprotection of a pair of Cys(Trt) residues is a widely applied procedure (see Vol.E22b, Sections 6.1.2-6.1.4). Finally, 5-trityl groups are efficiently cleaved with metal ions such as mercury(II) and silver(I),t 51 or with thalhum(III) trifluoroacetate.P ... 

In similar studies, Matsumura and coworkers later found that iodine-mediate anodic oxidation of methyl phenylacetate anion having Bu4N counterion provided the corresponding succinate in good yield and with high d, /-selectivity (d, J/meso 3.5) [371]. 

Regioselective de-O-benzylation. An alternative strategy to partially benzylated carbohydrates has been accomplished by selective de-O-benzylation of easily available polybenzylated precursors. This has been achieved in limited cases by catalytic hydrogenolysis [37], catalytic hydrogen-transfer cleavage [38], acetolysis [39], hypoiodite fragmentation [40], iodine-mediated addition-elimination sequences [41], or use of Lewis acids [42]. 

The Bohlmann-Rahtz reaction is a classic pyridine synthesis that has been studied and modified in many ways. Bagley et al. has elaborated on his previous work and reported an iodine-mediated catalytic Bohlmann-Rahtz reaction of aminodienone intermediates <05SL649>. This modified process is reported to be rapid at ambient temperatures resulting in good yields. Moreover, Bagley and co-workers presented a one-pot, three-component Bohhnann-Rahtz reaction to synthesize 2,3,6-trisubstituted and 2,3,4,6-tetrasubstituted pyridines 8 and 9 from P-ketoesters 10 and alkynes 11 as shown in Seheme 3 <05JOC1389>. 

In an Arbuzow reaction phosphite tricsters can be immobilized to obtain phosphorothiolates. Iodine-mediated transesterification of phosphorothiolates leads to cyclic phosphate of oligonucleotides [238],... 

The synthesis of the spirocyclic core [70-77] is obviously the most difficult task, the biomimetic approach being the most frequent way of preparing it. The strategy is based on the hipervalent iodine-mediated oxidative hydroxylation of a tyrosinal derivative followed by a cis-bisepoxidation. The shortest way [75] involved the introduction of the side chain as an amide of tyrosine ethyl ester. Aranorosin was obtained after DIBAL reduction to the aldehyde, oxidation to the dienone with phenyliodosyl bis(trifluoroacetate) (PIFA) and final epoxidation (Scheme 24). 

Scheme 5. (Diacetoxyiodo)benzene-iodine-mediated formation of pyran and furan derivatives...

A distinctly different reaction cascade leading to tetrahydrofurans is illustrated in Scheme 40 [74]. It was proposed that these reactions proceed by iodine-mediated deoxygenation of the peroxyl radical to an alkoxyl radical, which undergoes intramolecular C-H abstraction to form a y9-keto radical [74], Elimination of an a-hydrogen atom generates an enone, which is ultimately captured intramolecularly by conjugate hydroxyl addition to give a tetrahydrofuran (Scheme 40). 

Iodine-mediated oxidative cyclization methodology can also be applied to the synthesis of 1,2,4,5-oxathiadiazines 135 from the 1,5-bis-acylated thiocarbohydrazides 185 (Scheme 29) <2004IJH151>. 

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