Iodination lithiation

Conjugate addition of the complete allylic alcohol fragment is possible with the mixed cuprate reagents 33 prepared by asymmetric reduction (chapter 26) of acetylenic ketones 29 to give the alcohols 30, protection as a silyl ether 31 and hydroboration-iodination. Lithiation and reaction with hexynyl copper (I) gives the mixed cuprate 33 from which the less stable anion is transferred selectively to an enone.3 This approach has been widely used in the synthesis of prostaglandins. 

Lithiobutadienes 35 can easily be prepared from zirconacyclopentadienes by an iodination-lithiation sequence. The dilithiobutadienes 35 generated reacted with unactivated alkynes afforded substituted benzenes 36 via a formal [4 + 2] cycloaddition (Scheme 11.14) [16]. 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

Both 4,6- and 3,4-dimethoxydibenzofurans were brominated at C-l [84AHC(35)2]. Iodination of 3 follows the same trends as other halogena-tions (65MI1). Dibenzofuran is lithiated at the 4- and thallated at the 2-position, providing access to 2- and 4-iodo derivatives (57IZV1391). 

Introduction of an iodine to C-2 of indole can be accomplished using lithium derivatives. Since direct iodination tends to give mixtures it is essential to activate the 2-position at the expense of the inherently more reactive 3-position. This has been done by lithiating 1-f-butoxycarbonylin-doles (25) and then converting them into iodo derivatives before deprotection (85JHC505) (Scheme 19). Alternatively carbon dioxide can be used... 

Halogen exchange with metallic derivatives provides a powerful means of introducing iodine into specific quinoline sites. It has proved possible to prepare 2-, 3-, and 4-iodoquinolines from the trimethylstannyl [82H(19)168] or lithium derivatives [86S670]. Protected 2-aminoquinoline, lithiated at C-3, was quenched with iodine to give a 90% yield of the 3-iodo derivative (86S670). 

The attempted exchange reaction between 27 and phenylbismuth diiodide gave only intractable products. Apparently the bismole 31 is unstable under these Lewis acidic conditions. However, iodination of 27 gave 30 which, on lithiation followed by reaction with phenylbismuth diiodide, afforded the desired l-phenyl-2,5-dimethylbismole (31)," which could be... 

The lithiation of 3-haloindoles represents an excellent method for the preparation of other 2,3-dihaloindoles. For example, treatment of 4 with LDA followed by quenching with CNBr affords 2,3-dibromoindole 7 in good yield [13], and quenching with iodine furnishes 3-bromo-2-iodoindole 8 [14],... 

By taking advantage of the C(2) activation, 2-allyloxy-3-iodopyridine (173) was prepared by an SNAr displacement of 2-chloro-3-iodopyridine with sodium allyloxide [137]. 2-Chloro-3-iodopyridine was prepared by orrto-lithiation of 2-chloropyridine followed by iodine quench. The intramolecular Heck reaction of allyl ether 173 under Jeffery s ligand-free conditions resulted in 3-methylfuro[2,3-6]pyridine (174). 

Lithiothiophene, arising from lithiation of thiophene with n-BuLi, was treated with iodine to give 2-iodothiophene, which was allowed to react with sodium malononitrile in the presence of catalytic PdCl2(Ph3P)2 to afford thienylmalononitrile 18. Interestingly, a-metalation of ethyl 3-... 

Iodobenzofuran was readily prepared by lithiation of benzofuran followed by iodine quench [8]. Bromination of benzofuran with bromine gave 2,3-dibromobenzofuran, which, when subjected to a regioselective halogen/metal exchange at the C(2) position with n-BuLi followed by quenching with methanol furnished 3-bromobenzofuran [9]. 

DIRECTED ALDOL CONDENSATIONS threo-4-HYDROXY-3-PHENYL-2-HEPTANONE, 54, 49 DIRECTED LITHIATION OF AROMATIC COMPOUNDS (2-DIMETHYL-AMINO- 5-METHYLPHENYL) DI-PHENYLCARBINOL, 53, 56 DIRECT IODINATION OF POLYALKYL-BENZENES IODODURENE, 51, 94 Disiamylborane, 53, 79 Disodium hydroxylaminedisulfo-nate, 52, 83... 

Scheme 8.13 and Eqs. 8.6-8.10 reveal that lithiated methoxyallene 42 is sufficiently reactive towards a variety of electrophiles such as alkyl halides [44, 45], ethylene oxide [12c], tosylated aziridine 45 [46], dimethyl disulfide [12b], trialkylstannyl and trialkylsilyl chlorides [47, 48] and iodine [49]. These substitution reactions proceed with excellent regioselectivity and the corresponding a-functionalized products are obtained in good to high yields. An exceptional case was found by treatment of 42 with a guanidinium salt, which led to a 60 40 mixture of a- and y-adducts 50 and 51 (Eq. 8.11) [50],... 

Naphthalene-catalyzed (5%) lithiation of the diiodinated ketal 205 afforded directly the cyclobutane derivative 206, a i5-iodinated organoUthium compound probably being involved (Scheme 71). In this case, a 5-elimination of lithium iodide is preferred to a y- or 5-elimination of lithium aUcoxide. 

Lithiation and mercuration are directed by the oxygen atom and occur at the 4-position, but thallation, achieved by treatment of dibenzofuran with thallium(III) isobutyrate at 110°C, affords the 2-thallium di(isobutyrate), which may be converted to the 2-iodo compound by reaction with iodine. Mercuration is achieved by treatment of dibenzofuran with mercuryfll) acetate at 150°C, and the resultant 4-mercuric acetate (56%) may also be converted to the iodo compound. ... 

Finally, the peculiar formation of iodoalkynes from iodine and acetylenes with relatively low (< 25) pK values in liquid ammonia should be mentioned [121]. The most likely intermediates occurring are acetylide "anions" formed in very low concentrations from the acetylene and the base ammonia. The conversions proceed very slowly and iodinadon of the lithiated alkynes in the same solvent is undoubtedly a far superior method. 

Preparation of Iodoacetylenes from Lithiated Acetylenes and Iodine in Liquid Ammonia... 

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