Reductive elimination hydrazones

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

In 1913, Kishner observed in one instance that under standard Wolff-Kishner reduction conditions, 2-hydroxy-2,6-dimethyloctan-3-one underwent eliminative reduction upon treatment with hydrazine hydrate and base at elevated temperatures to afford 2,6-dimethyloctan-2-ene (Scheme 7). This same reaction was later found to occur in the case of a-methoxy ketones and has since been referred to as the Kishner eliminative reduction. The reaction entails initial formation of the hydrazone and elimination of the a-substituent to afford the intermediate alkenyldiazene, which subsequently collapses to the desired alkene. Given the facile transformation of ketones into a-halo ketones, these conditions have been used to introduce alkenes regioselectively in the 2a-halocholestan-3-one series as shown in Scheme 8. Yields of 2-cholestene parallel the resistance of the a-halogen to undergo competitive elimination reactions. 

Reductive elimination of sugar tosyl hydrazones using sodium hexamethyl-disilazide/LAH provides a route to various homochiral dioxolanes. Thus, D-xylose, D-arabinose and D-xylose derivatives 71-73 were converted to isopro-pylidene acetals 74-76, while D-xylose derivatives 77 and 78 provided 6-membered acetals 79 and 80, respectively. ... 

Wolff-Kishner reduction—Hydrocarbons from hydrazones—Gope elimination s. 17, 106... 

Potassium terUbutoxide Reaetions in dimethyl sulfoxide Wolff-Kishner reduction Hydrocarbons from hydrazones Cope elimination... 

To reduce the hydrazone bonds to more stable linkages, cool the cell suspension to 0°C and add an equal volume of 30 mM sodium cyanoborohydride in PBS. Incubate for 40 minutes. Note If the presence of a reducing agent is detrimental to protein activity, eliminate the reduction step. In most cases, the hydrazone linkage is stable enough for fluorescent labeling experiments. 

Diels-Alder reactions of a,fi-unsaturatedN,N-dimethylhydrazones.1 These readily available hydrazones can function as 1-amino-l-aza-l,3-dienes in Diels-Alder reactions. Thus, 1 undergoes regioselective cycloaddition with various electrophilic dienophiles to give tetrahydropyridines such as 2 and 3. Unfortunately, removal of the dimethylamino group with zinc and acetic acid (or other reagents) also effects reduction of the double bond. The initial adduct from cycloaddition of 1 with naphthoquinone is unstable and undergoes spontaneous elimination of the elements of dimethylamine to give the aromatic adduct 4. 

The unsubstituted hydrazones derived from aromatic ketones and aldehydes are converted to the corresponding alkyl chlorides, in high yield, under Swern oxidation conditions. In this unusual oxidation/reduction sequence, the substrate undergoes a net reduction. Unsubstituted hydrazones derived from cyclohexyl ketones yielded elimination products. The mechanism in Scheme 7 has been postulated.111... 

Aldehydes and ketones on complete reduction give alkanes by three different methods that are complementary to each other. The Woff-Kishner reduction is done under basic conditions and is suitable for compounds that might be sensitive to acid (Following fig.). The reaction involves the nucleophilic addition by hydrazine followed by elimination of water to form a hydrazone. The mechanism is the... 

Because disconnection of a-alkoxy-y-amino acid 28 calls for (3-alkoxyhydra-zone 30, the potential for (3-elimination of the alkoxy group from the hydrazone precursor 30 (Scheme 7) makes non-basic conditions critical. In fact, treatment of 30 with TBAF in THF led to just such a (3-elimination (Marie, University of Iowa, unpublished). However, the manganese-mediated radical addition of isopropyl iodide proceeded in 77% yield, without any evidence of (3-elimination, to afford 31 as a single diastereomer. Reductive removal of the chiral auxiliary and oxidation to the carboxylic acid gave 28 in good overall yield [103]. 

A slighdy more vigorous method, known as the Wolff-Kishner reduction, is driven by the elimination of nitrogen gas from a hydrazone. Hot concentrated sodium hydroxide solution deprotonates the hydrazone, which can then eliminate an alkyl anion—a reaction you would usually be wary of writing, but which is made possible by the thermodynamic stability of N2. 

In aprotic media the rate of cleavage of the radical anion of Y,Y-dimethylhydra-zones of arylaldehydes is a linear function of the reversible reduction potential of the hydrazone. The electrogenerated base may induce an elimination of amine to a nitrile [230]. 

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