Kornblum synthesis

If the Kornblum synthesis is to be applied to halo carboxylic esters it is essential to add phloroglucinol whether dimethylformamide or dimethyl sulfoxide is used as solvent, because otherwise the -(hydroxyimino) ester is the predominant product.655,cf 164,652... 

The reaction of alkyl halides with metal nitrites is one of the most important methods for the preparation of nitroalkanes. As a metal nitrite, silver nitrite (Victor-Meyer reaction), potassium nitrite, or sodium nitrite (Kornblum reaction) have been frequently used. The products are usually a mixture of nitroalkanes and alkyl nitrites, which are readily separated by distillation (Eq. 2.47). The synthesis of nitro compounds by this process is well documented in the reviews, and some typical cases are listed in Table 2.3.92a Primary and secondary alkyl iodides and bromides as well as sulfonate esters give the corresponding nitro compounds in 50-70% yields on treatment with NaN02 in DMF or DMSO. Some of them are described precisely in vol 4 of Organic Synthesis. For example, 1,4-dinitrobutane is prepared in 41 -46% yield by the reaction of 1,4-diiodobutane with silver nitrite in diethyl ether.92b 1-Nitrooctane is prepared by the reaction with silver nitrite in 75-80% yield. The reaction of silver nitrite with secondary halides gives yields of nitroalkanes of about 15%, whereas with tertiary halides the yields are 0-5%.92c Ethyl a-nitrobutyrate is prepared by the reaction of ethyl a-bromobutyrate in 68-75% yield with sodium nitrite in DMF.92d Sodium nitrite is considerably more soluble in DMSO than in DMF as a consequence, with DMSO, much more concentrated solutions can be employed and this makes shorter reaction times possible.926... 

The key step in the synthesis of the branched sugars presented in Scheme 7.2 is a Kornblum reaction of the nitropyranose. A mixture of anomers is obtained in the reaction of nitrofuranose, but the reaction with nitropyranose proceeds diastereoselectively to give a single product with an equatorially oriented side chain. 

From the foregoing it can be seen that the nitro group can be activated for C C bond formation in various ways. Classically the nitro group facilitates the Henry reaction, Michael addition, and Diels-Alder reaction. Kornblum and Russell have introduced a new substitution reaction, which proceeds via a one electron-transfer process (SrnI). The SrnI reactions have recently been recognized as useful tools in organic synthesis. All these reactions can be used for the preparation of alkenes as described in this chapter. 

The synthesis of aliphatic nitro compounds from the reaction of alkyl halides with alkali metal nitrites was discovered by Kornblum and co-workers and is known as the modified Victor Meyer reaction or the Kornblum modification. The choice of solvent in these reactions is crucial when sodium nitrite is used as the nitrite soiuce. Both alkyl halide and nitrite anion must be in solution to react, and the higher the concentration of nitrite anion, the faster the reaction. For this reason, both DMF and DMSO are widely used as solvents, with both able to dissolve appreciable amounts of sodium nitrite. Although sodium nitrite is more soluble in DMSO than DMF the former can react with some halide substrates.Urea is occasionally added to DMF solutions of sodium nitrite to increase the solubility of this salt and hence increase reaction rates. Other alkali metal nitrites can be used in these reactions, like lithium nitrite,which is more soluble in DMF than sodium nitrite but is also less widely available. 

N. Kornblum, The Synthesis of Aliphatic and Alicyclic Nitro Compounds, Org. React.,... 

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

Disubstituted thiophenes 96 and 1,2,5-tri- and 2,5-disubstituted pyrrole derivatives 97 are available readily from m-3,6-disubstituted-3,6-dihydro-l,2-dioxins in a one-pot synthesis. The reaction proceeds by an initial Kornblum-de la Mare rearrangement of the 3,6-dihydro-l,2-dioxin to its isomeric 1,4-diketone followed by the condensation with Lawesson s reagent, ammonium carbonate, or a primary amine (Scheme 21) <2002TL3199>. 

Kornblum, N. The synthesis of aliphatic and alicyclic nitro compounds. In Cope, A. C., Ed.-in-Chief "Organic Reactions", Vol. 2 John Wiley Sons, Inc. New York, 1962 pp. 101-156. 

The o- and /z-nitrobenzyl derivatives5 and the analogous / -nitrocumyl derivatives5,313,6615, especially the chlorides, have been extensively studied and reviewed by Kornblum and coworkers. They react with a wide range of organic and inorganic nucleophiles, providing a novel and powerful means of synthesis. 

A one-pot synthesis of 2,5-disubstituted thiophenes 595 from 3,5-dihydro-l,2-dioxines 593 has been reported. The reaction proceeds by a Kornblum-de la Mare rearrangement to 1,4-diketones 594 followed by sulfuration with LR (Scheme 90) <2002TL3199>. 

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... 

KONIG Benzoxazin synthesis 214 KORNBLUM Aldehyde synthesis 215 KOSER Tosylation 216 Kostaneeki 321... 

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. 

Kornblum, N. The synthesis of aliphatic and alicyclic nitro compounds. Org. React. 1962,12, 101-156. 

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-... 

In an approach to phytuberin, the vicinal dinitroacetal (102) was prepared and the nitro groups reductively eliminated in a Kornblum olefin synthesis (Scheme 161).3 ... 

Kornblum J, Kreiswirth B, Projan SJ, Ross H, Novick RP (1990) agr a polycistronic locus regulating exoprotein synthesis in Staphylococcus aureus. In Novick RP (ed) Molecular Biology of the Staphylococci. VCH Publishers, New York, pp 373-402... 

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