Diazo ketones reduction

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

Dauben et al. (15) applied the Aratani catalyst to intramolecular cyclopropanation reactions. Diazoketoesters were poor substrates for this catalyst, conferring little asymmetric induction to the product, Eq. 10. Better results were found using diazo ketones (34). The product cyclopropane was formed in selectivities as high as 77% ee (35a, n = 1). A reversal in the absolute sense of induction was noted upon cyclopropanation of the homologous substrate 34b (n = 2) using this catalyst, Eq. 11. Dauben notes that the reaction does not proceed at low temperature, as expected for a Cu(II) precatalyst, but that thermal activation of the catalyst results in lower selectivities (44% ee, 80°C, PhH, 35a, n = 1). Complex ent-11 may be activated at ambient temperature by reduction with 0.25 equiv (to catalyst) DIBAL-H, affording the optimized selectivities in this reaction. The active species in these reactions is presumably the aluminum alkoxide (33). Dauben cautions that this catalyst slowly decomposes under these conditions. 

Hydriodic acid is a reagent of choice for reduction of alcohols [225], some phenols [225], some ketones [227, 228], quinones [222], halogen derivatives [22S, 229], sulfonyl chlorides [230], diazo ketones [231], azides [232], and even some carbon-carbon double bonds [233]. Under very drastic conditions at high temperatmes even polynuclear aromatics and carboxylic acids can be reduced to saturated hydrocarbons but such reactions are hardly ever used nowadays. 

Non-functionalized aliphatic diazo compounds are fairly rare, and so are their reductions. Good examples of the reduction of diazo compounds to either amines or hydrazones are found with a-diazo ketones and a-diazo esters (pp. 124, 125, 160). 

Types of compounds are arranged according to the following system hydrocarbons and basic heterocycles hydroxy compounds and their ethers mercapto compounds, sulfides, disulfides, sulfoxides and sulfones, sulfenic, sulfinic and sulfonic acids and their derivatives amines, hydroxylamines, hydrazines, hydrazo and azo compounds carbonyl compounds and their functional derivatives carboxylic acids and their functional derivatives and organometallics. In each chapter, halogen, nitroso, nitro, diazo and azido compounds follow the parent compounds as their substitution derivatives. More detail is indicated in the table of contents. In polyfunctional derivatives reduction of a particular function is mentioned in the place of the highest functionality. Reduction of acrylic acid, for example, is described in the chapter on acids rather than functionalized ethylene, and reduction of ethyl acetoacetate is discussed in the chapter on esters rather than in the chapter on ketones. 

The Dauben-Walker approach has yielded the smallest and most strained fenestrane known to date Following the intramolecular Wadsworth-Enunons cyclization of 443 which also epimerizes the butenyl sidechain to the more stable exo configuration, intramolecular photocycloaddition was smoothly accomplished to provide 444. Wolff-ELishner reduction of this ketone afforded the Cj-symmetric hydrocarbon 445. Application of the photochemical Wolff rearrangement to a-diazo ketone 446 p,ve 447. 

Reduction of N-nitro compounds 0-5 Hydrolysis of diazo ketones... 

Hydrolysis of enol esters 0-76 Reduction of halo ketones 0-78 Reduction of hydroxy ketones 0-82 Reduction of diazo ketones or nitro ketones... 

GRUNDMANN ALDEHYDE SYNTHESIS. Transformation of an acid into an aldehyde of the same chain length by conversion of the acid chloride via the diazo ketone to the acetoxy ketone, reduction with aluminum isopropoxide and hydrolysis to the glycol, and cleavage with lead tetraacetate. 

Following preliminary work,528 ( )-chelidonine (118) has been synthesized from the acid (115) (obtained from methylenedioxyhomophthalic anhydride and TV-methyldimethoxybenzalimine) by its conversion into the diazo-ketone (116), cyclization of this (using trifluoroacetic acid) to the keto-lactam (117), and reduction with lithium aluminium hydride.529,530... 

Certain aryl-substituted a- and /S-amino Intones have been successfully reduced to amino alcohols by catalytic hydrogenation over palladium, platinum, or nickel catalysts. Cleavage of the carbon chain sometimes occurs during catalytic hydrogenation of /S-amino ketones. Fair yields of the amino alcohols ate obtained in these cases by reduction with sodium amalgam in dilute acid or aluminum amalgam and water. /S-Amino aldehydes from the Mannich reaction (method 444) are reduced in excellent yields to amino alcohols by lithium aluminum hydride or by catalytic hydrogenation over Raney nickel. Lithium aluminum hydride reduces diazo ketones to 1-amino-2-alkanols (93-99%)- ... 

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