4-iodo pyridine derivative

Heteroatom rings, such as that found in quinoline derivatives, can be generated from amino-ketones with [hydroxy(tosyloxy)iodo]benzene and perchloric acid. Cyclic imines are converted to pyridine derivatives with NCS and then excess sodium methoxide. ... 

L-Asparagine was used for the synthesis of chiral pipecolates, building blocks for the alkaloid apovincamine. The iodo compound, formed in a multistep transformation from L-asparagine, was cyclized with LDA and ethyl iodide to give the pyridine derivative with a defined configuration (Scheme 36) (85JOC1239). 

Compound 85 was dehydrogenated at 300° over palladium black under reduced pressure to a pyridine derivative 96 which was independently synthesized by the following route. Anisaldehyde (86) was treated with iodine monochloride in acetic acid to give the 3-iodo derivative 87. The Ullmann reaction of 87 in the presence of copper bronze afforded biphenyldialdehyde (88). The Knoevenagel condensation with malonic acid yielded the unsaturated diacid 91. The methyl ester (92) was also prepared alternatively by a condensation of 3-iodoanisaldehyde with malonic acid to give the iodo-cinnamic acid (89), followed by the Ullmann reaction of its methyl ester (90). The cinnamic diester was catalytically hydrogenated and reduced with lithium aluminium hydride to the diol 94. Reaction with phosphoryl chloride afforded an amorphous dichloro derivative (95) which was condensed with 2,6-lutidine in liquid ammonia in the presence of potassium amide to yield pyridine the derivative 96 in 27% yield (53). 

Regio- and stereo-controlled iodocyclizations of allylic trichloroacetimidates provide a route to cw-hydroxyamino sugar from hexenopyranosides. For example, conversion of the hydroxyl of compound 117 into the trichloroacetimidate 118 followed by IDCP-mediated intramolecular cyclization, gives iodo-oxazoline derivative 119, which is reduced (Bu3SnH) and hydrolyzed (pyridine, TsOH) to afford IV-acetyldaunosamine methyl glucoside 120 (O Scheme 57) [95]. 

Subsequent protic workup releases the aromatic compound. The metalative Reppe reaction can also be used to prepare iodo-substituted or homologated aromatics by treatment of the titanium aryl compound with iodine or an aldehyde, respectively. This procedure has recently been extended to include pyridine derivatives (254 and 255), where the titanacyclopentadiene intermediate can be treated with sulfonylnitriles to afford pyridines after protic workup.192 As with the alkyne cyclotrimerizations, treatment with the appropriate electrophiles affords iodo- and homologated pyridines. 

Only 2-pyridyl reverse C-nucleosides are known. Coupling saccharide free radicals 831 and 834 with protonated pyridine derivatives gave the 2-pyridyl reverse C-nucleosides 832 and 835, respectively. Free radical 831 was obtained by decarboxylative photolysis of the uronic acid derivative 830 in the presence of hypervalent iodine compounds (92TL7575 (Scheme 232), whereas free radical 834 was obtained by thermal homolysis of the carbon-iodine bond in the 6-iodo-6-deoxy-o-galactopyranose derivative 833 in the presence of benzoyl peroxide (93JOC959) (Scheme 233). 

The scope of various pyridine derivatives with 1-hexene was examined with L45c-Sc/[Ph3C][B(C6F5)4] as the catalyst (Table 5.8). The asymmetric alkylation of 2-Me, 2-Et, 2- Pr, 2- Bu, and 2-phenyl-substituted pyridines 188 could also be achieved similarly in high yields (83-94%) and enantioselectivity (up to 94 6 er) (entries 1-5). Notably, the C—H bond activation reaction occurred selectively at the pyridine unit rather than at the phenyl group in the case of 2-phenylpyridine, which is in contrast with the reactions catalyzed by late transition metal complexes. The iodo, bromo, and chloro substituents in the picoline substrates are well compatible (entries 6-8). No alkylation reaction was observed with unsubstituted pyridine or quinoline, probably due to the poisoning effect of the N atom of pyridine to the metal center. 

Chloro- and bromoaminopyridines are oxidized by persulfuric acid at 0° to their nitro derivatives thus, 3-chloro-, and 3-bromo-4-aminopyridine are converted to the respective 3-halo-4-nitropyridines. However, 4-araino-3-iodo-pyridine is not oxidized under these conditions. 4-Amino-2,3,5,6-tetrafluoro-pyridine is difficult to oxidize and requires refluxing peroxytrifiuoroacetic acid for 22 hours in order to yield the 4-nitro derivative. Potassium bromate has been used to oxidize S-amino-3-methyl-2-pyridone, but the product was not a nitro compound instead 3-hydroxy-6-methyl-2-aza-l,4-benzoquinone-4-(2,6-di-hydroxy-5-methyl-3-pyridyl)imine (IX-S7) was obtained. ... 

Reddy s group reported a silver-catalyzed annulation of enynyl azides to pyridine derivatives in 2015 [8], 3,6-Disubstituted pyridines were prepared in good yields through Ag-mediated aza-annulation of 2-en-4-ynyl azides which were derived from MBH-acetates of acetylenic aldehydes. 5-Iodo-3,6-Disubstituted pyridines can be prepared from enynyl azides having an electron-rich substituent on the alkyne functionality with I2 as the promoter (Scheme 2.5). 

The substituted 5,6-hexoseens may be prepared by treatment of appropriate 6-bromo or 6-iodo glycoside derivatives in pyridine or acetonitrile solution with silver fluoride or sulfate or, alternatively, with sodium meth-oxide in methanol solution 1 ), When the sugar lactol ring is labilized in these compounds by removal of the protecting groups, isomerization to the keto isomer occurs 128). 

Similar examples of regioselective metalation of 3-alkylpyridine-BF3 complexes with the use of TMP-zincate were reported by Michl and co-workers in 2002 [70]. The reaction occurred at the less hindered one of the two reactive positions, as evidenced by trapping of the pyridyl zincates with iodine to afford the 2-iodo-5-alkyl pyridine derivatives in good yields (Eq. 19). 

Pyridine and chloroacetic acid react normally to give the stable betaine derivative, but 2,5-dimethylpyrazine is quite different in its behavior. Chloroacetic acid is without action while both bromo- and iodo-acetic acid react smoothly, more rapidly in nitrobenzene than in... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

Several Sonogashira adducts of heteroaromatics including some pyridines (see Section 4.3) and pyrimidines underwent an unexpected isomerization [69]. This observed isomerization appeared to be idiosyncratic, and substrate-dependent. The normal Sonogashira adduct 100 was obtained when 2-methylthio-5-iodo-6-methylpyrimidine (99) was reacted with but-3-yn-ol, whereas chalcone 101, derived from isomerization of the normal Sonogashira adduct, was the major product when the reaction was carried out with l-phenylprop-2-yn-l-ol. 

Deprotonation readily occurs at C-7, and the resulting anion can further react with various electrophiles. Thus, treatment with BuLi at — 78 °C followed by reaction with diiodoethane was used to prepare the 7-iodo derivatives depicted in Table 2, while the 7-chloro derivatives were prepared by lithiation with lithium diisopropylamide (LDA), followed by reaction with CCI4. The 7-formyl derivative of the parent pyrazolo[l,5- ]pyridine has been prepared in 82% yield by reaction of the BuLi-generated anion with ethyl formate <2001JME2691>. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

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