Kornblum oxidation

AgBp4 (1.1 to I.Sequiv) DMSO (solvent) / room temp. 

C5H5N-O or 2-Me-C5H5N—0 / NaHC03 / solvent / heat Ganem oxidation 

With alkyl halide substrates, the first step of the oxidation is the Sn2 displacement of the halide with tosylate anion. Next the alkyl tosylate undergoes a second Sn2 reaction with the nucleophilic oxygen atom of the DMSO to form the alkoxysulfonium salt that undergoes deprotonation to give the alkoxysulfonium ylide, which upon a [2,3]-sigmatropic shift affords the carbonyl compound. In the case of a-halo carbonyl substrates, the deprotonation takes place at the more acidic a-carbon instead of the methyl group attached to the sulfur atom of the alkoxysulfonium salt. 

A tandem Kornblum ox/daf/on/imidazole formation reaction was used during the preparation of new fluorescent nucleotides by B. Fischer and co-workers.The adenosine monophosphate free acid was mixed with 10 equivalents of 2-bromo-(p-nitro)-acetophenone and dissolved in DMSO. The required pH value was maintained with the addition of DBU which also served as a base. The Kornblum oxidation of the alkyl halide yielded the glyoxal, which reacted in situ with the aromatic amine to form the desired imidazole derivative. 

The first total synthesis of the clerodane alkaloid solidago alcohol was achieved in the laboratory of H.-S. Liu, using a highly diastereoselective DIels-Alder cycloaddition as the key step. The installation of the 3-furyl side chain required the conversion of the bicyclic primary alkyl bromide to the corresponding aldehyde. This was accomplished by the modified Kornblum oxidation, which employed silver tetrafluoroborate to activate the substrate. 

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Koch-Haaf reaction, 17, 3 Kornblum oxidation, 39, 3 Kostaneki synthesis of chromanes, flavones, and isoflavones, 8, 3... 

The traditional oxidation of benzylic and other halides to the aldehyde using DMSO (Kornblum oxidation) has been known for about 35 vears246,362,363. Modified oxidations of this type using selenoxides364,365 and 2-nitropropane366,367 have proved more versatile since other functional groups that are sensitive to the traditional oxidation procedure may be tolerated. In the reaction with 2-nitropropane, allylic halides are readily converted into aldehydes with retention of the alkene geometry. 

Evans and Mitch( 101 elaborated this synthesis to afford a general approach to morphinans and to include a total synthesis of ( )-morphine (Scheme 3.7). The diastereomerically pure aziridinium salt, 43, was prepared as illustrated and converted to the aldehyde (44) in 95% yield simply by dissolving in anhydrous DMSO at ambient temperature (Kornblum oxidation). Lewis acid catalyzed ring closure occurred in high yield (80%) to the isomorphinan-10-ol... 

A number of simple analogs of the antipsoriatic agent anthralin (dithranol) were prepared by K. Muller and co-workers by changing the positions of the hydroxyl groups as well as adding new functional groups into various positions of the anthracenone nucleus. The benzyl bromide functionality was converted to the corresponding aldehyde by the Kornblum oxidation in fair yield. 

A novel synthetic approach was developed by R.E. Taylor et al. for the preparation of the triene portion of the biologically active polyketide apoptolidin. The allylic chloride substrate was prepared from an allylic alcohol via a thionyl chloride mediated rearrangement. Next, the allylic chloride was subjected to the Ganem oxidation by treating it with five equivalents of trimethylamine A/-oxide (TMANO) in DMSO at room temperature to obtain the desired a,p-unsaturated aldehyde. Interestingly, the original Kornblum oxidation conditions were not well suited for this system because of the required high reaction temperature. 

Novel fluorescent ATP analogues where the two tertiary carbons of the etheno-moiety of A A -etheno adenosine have been modified by the introduction of a /7-nitro or a / -amino-phenyl group and a hydroxy moiety (100) have been prepared via a Kornblum oxidation reaction and imidazole formation. These compounds exhibited relative stability towards type II ATPDase. ... 

Nucleoside Pyrophosphates. - The synthesis of 8-aryl-3-P-o-ribofuranosylimiazo[2,l-i]purine 5 -phosphates (122) from AMP or ATP has been described. To access these fluorescent nucleotide derivatives, a combination of Kornblum oxidation reaction and imidazole formation was employed. For this conversion, the appropriate adenosine phosphate, present in its free acid form, was treated with p-nitro-acetophenone in DMSO in the presence of DBU. Treatment of a 5-(chloroethyl)-4-(triazole-l-yl)pyrimidine-nucleoside with benzylhydrazine offered the 6,6-bicyclic pyrimido-pyradazin-7-one, the precursor to (123). This triphosphate was used as a substrate for DNA polymerases. ... 

Oxidation [1, 303-308] In a search for a convenient synthesis of ninhydrin, Schipper et a/.35a applied the Kornblum oxidation to 2-bromo-l,3-indanedione O and indeed obtained ninhydrin (2) in 36% yield. The bromo compound (1) was prepared by bromination of 1,3-indanedione with cupric bromide (1, 161). Subsequent-... 

Tricarbonyl compounds. 1,3-Dicarbonyl compounds can be converted into 1,2,3-tricarbonyl compounds by monobromination (bromine and pyridine or triethylamine) followed by Kornblum oxidation (1, 303) in DMSO at 70-80° ... 

Several interesting variants on the Kornblum oxidation have been published this year. These include a modification of the original conditions by the inclusion of sodium hydrogen carbonate... 

Other references related to the Kornblum oxidation are cited in the literature. ... 

In the Kornblum oxidation, a primary alkyl halide is oxidized to the aldehyde with DMSO and NaHC03, typically with microwave heating ... 

The formation of dicarbonyl compounds by this reagent is a variation of the Kornblum oxidation and presumably involves acid-catalyzed iodination of the carbonyl compound (1) to give an a-iodo ketone (2) which undergoes displacement by DMSO to... 

The first iodine-catalyzed synthesis of 2-alkyl substituted oxazoles 130 by a decarboxylative domino reaction was reported. Aryl methyl ketones 128 were transformed in situ into a-iodo ketones and then, by the Kornblum oxidation, into 1,2-diketones. After the addition of the a-amino acid 129, an l2-mediated cyclization/decarboxylation gave oxazoles 130. The reaction proceeds better if the Ar has electron-donating substituents and if the R group is a branched alkyl chain or phenyl residue. The reaction used oxone to regenerate iodine (13JOC6065). 

Based on control experiments run by the authors, a possible mechanism was presented, which is shown in Scheme 38. Initial halogenation of acetophenone (81) with iodine provides an a-iodo ketone 82, which is then converted to the phenylglyoxal (83) under Kornblum oxidation reaction conditions. The proposed subsequent step is the condensation and addition of 2-aminobenzamide (80) to give compound 84, which is then oxidized and aromatized in the presence of iodine. 

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