Carbonyl compounds substituted acetic acids, synthesis

The carbenoid reaction between alkyl diazoacetates and enol ethers, enol acetates and silyl enol ethers furnishes P-oxycyclopropane carboxylates (see Tables 2, 4, 5, 6, 7 and Scheme 5). The recently recognized synthetic versatility of these donor/acceptor-substituted cyclopropanes i 2,io3) (precursors of 1,4-dicarbonyl and P, 7-unsaturated carbonyl compounds, 4-oxocarboxylic acids and esters, among others) gave rise to the synthesis of a large number of such systems with a broad variation of substituents p-acetoxycyclopropanecarboxylates , p-alkoxy- or p-aryloxysubstituted cyclopropanecarboxylates 2-alkoxy-1-methyl-1-cy-... 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

Synthetic methods for preparation of 1,2,4,5-tetroxanes have been reviewed recently <2001COR601, 2002RMC113>. The most general method involves acid-catalyzed addition of hydrogen peroxide to carbonyl compounds and subsequent cyclization of the hydroperoxide intermediates. The direct synthesis is carried out normally in the presence of either sulfuric, perchloric, or methanesulfonic acids and affords symmetrically substituted tetroxanes (Equation 26). In many cases, for example, where the carbonyl compound is unsubstituted in the a-position, tetroxanes are contaminated with hexaoxonanes and open-chain hydroperoxides. Selective removal of the more reactive hydroperoxides can be achieved with dimethyl sulfide or potassium iodide. Recrystallization usually removes residual hexaoxonanes but, failing that, heating the mixture with perchloric acid in acetic acid can convert hexaoxonanes to tetroxanes or convert the thermodynamically less stable hexaoxonanes to more water-soluble lactones, which may facilitate the purification process <2002RMC113>. 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

Iodosylbenzoic acid (85) is also a convenient recyclable hypervalent iodine oxidant for the synthesis of a-iodo ketones by oxidative iodination of ketones [88], Various ketones and p-dicarbonyl compounds can be iodinated by this reagent system under mild conditions to afford the respective a-iodo substituted carbonyl compounds in excellent yields. The final products of iodination are conveniently separated from by-products by simple treatment with anionic exchange resin Amberlite IRA 900 HCOs" and are isolated with good purity after evaporation of the solvent. The reduced form of the hypervalent iodine oxidant, 3-iodobenzoic acid (59), can be recovered in 91-95% yield from the Amberlite resin by treatment with aqueous hydrochloric acid followed by extraction with ethyl acetate [88]. 

In 1999, Katritzky reported a novel [3+2+1] synthesis of 2,4,6-trisubstituted pyridine derivatives that used the Michael addition of a-benzotriazolyl ketones to a,P-unsaturated carbonyl compounds. This reaction resembles the Krohnke pyridine synthesis and is an extension of Katritzky s earlier studies with benzotriazolyl derivatives that provided access to pyridones, 2-thiopyridones, 5-alkyl-2,4-diphenylpyridines and 2-aminopyridines. This approach is attractive as both components are readily synthesized or commercially available. The availability of these starting materials allows for an efficient access to structurally diverse 2,4,6-triaryl pyridines when combined with ammonium acetate in acetic acid at reflux. In addition, it is possible to access fused 2,3,4,6-tetrasubstituted pyridines from the requisite fused bicyclic ketone starting material. The preparation of the pyridine ring via benzotriazole methodology has resulted in improved yields for many compounds and the opportunity to synthesize molecules with a substitution pattern that would be difficult to prepare by other methods. 

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