Esters dehydrogenative amidation

This section contains dehydrogenations to form alkenes and unsaturated ketones, esters and amides. It also includes the conversion of aromatic rings to alkenes. Reduction of aryls to dienes is found in Section 377 (Alkene-Alkene). Hydrogenation of aryls to alkanes and dehydrogenations to form aryls are included in Section 74 (Alkyls from Alkenes). 

Most examples of quinone dehydrogenations adjacoit to have been earned out on steroidal ketones and are essentially limited to readily enolizable species. Reactions on esters and amides (Table 8) are far less common and, because of their relatively low ease of enolization, require hanh conditions. Thus, unless stabilization of the intermediate carbonium ion is possible, - elevated temperatures and prolonged reaction times are required (Table 8), which increases the incidence of unwanted side reactions. Frequent by-products are those arising as a result of Diels-Alder reactions or Michael addition to the quinone." Allylic alcohols may be rapidly oxidized to aldehydes or ketones under these conditions and requite prior protection. 

This section contains dehydrogenations to form alkenes and unsaturated ketones, esters and amides. It also includes the conversion of aromatic rings to alkenes. 

On the other hand, the dehydrogenative amidation proved to be also sensitive to the electronic properties of the amines. Thus, with electron-poor amines, which display a low nucleophilic character, the formation of the hemiaminal intermediate is disfavored. As a consequence, substrates like anilines usually lead to low or moderate conversions, even at elevated temperatures or after long reaction periods, and large amounts of the corresponding esters by-products are formed. In this context, the ruthenium catalysts have conduced, in general, to quite disappointing results [114, 115, 117, 124], In fact, only gold nanoparticles have proven to be useful with this type of amines [132]. 

Novel carbonylative carbocyclizations of 1,6-diynes promoted by Ru3(CO)i2/P(hex-c)3 in the presence of HSiMc2Bu-Z give bicyclic o-catechol derivatives by incorporating two carbon monoxide molecules as the 1,2-dioxyethenyl moiety (equations 148 and 149)346. This reaction is tolerant of functional groups such as ester, ketone, ether and amide. The disilylated product 366 is formed through dehydrogenative silylation of the initially formed mono-silyl product 365 under the reaction conditions. 

Compound 85 was dehydrogenated at 300° over palladium black under reduced pressure to a pyridine derivative 96 which was independently synthesized by the following route. Anisaldehyde (86) was treated with iodine monochloride in acetic acid to give the 3-iodo derivative 87. The Ullmann reaction of 87 in the presence of copper bronze afforded biphenyldialdehyde (88). The Knoevenagel condensation with malonic acid yielded the unsaturated diacid 91. The methyl ester (92) was also prepared alternatively by a condensation of 3-iodoanisaldehyde with malonic acid to give the iodo-cinnamic acid (89), followed by the Ullmann reaction of its methyl ester (90). The cinnamic diester was catalytically hydrogenated and reduced with lithium aluminium hydride to the diol 94. Reaction with phosphoryl chloride afforded an amorphous dichloro derivative (95) which was condensed with 2,6-lutidine in liquid ammonia in the presence of potassium amide to yield pyridine the derivative 96 in 27% yield (53). 

This chapter highlights the ruthenium-catalyzed dehydrogenative oxidation and oxygenation reactions. Dehydrogenative oxidation is especially useful for the oxidation of alcohols, and a variety of products such as ketones, aldehydes, and esters can be obtained. Oxygenation with oxo-ruthenium species derived from ruthenium and peroxides or molecular oxygen has resulted in the discovery of new types of biomi-metic catalytic oxidation reactions of amines, amides, y3-lactams, alcohols, phenols, and even nonactivated hydrocarbons tmder extremely mild conditions. These catalytic oxidations are both practical and useful, and ruthenium-catalyzed oxidations will clearly provide a variety of futrue processes. 

The spectrum of applications of potassium permanganate is very broad. This reagent is used for dehydrogenative coupling [570], hydrox-ylates tertiary carbons to form hydroxy compounds [550,831], hydroxylates double bonds to form vicinal diols [707, 296, 555, 577], oxidizes alkenes to a-diketones [560, 567], cleaves double bonds to form carbonyl compounds [840, 842, 552] or carboxylic acids [765, 841, 843, 845, 852, 869, 872, 873, 874], and converts acetylenes into dicarbonyl compounds [848, 856, 864] or carboxylic acids [843, 864], Aromatic rings are degraded to carboxylic acids [575, 576], and side chains in aromatic compounds are oxidized to ketones [566, 577] or carboxylic acids [503, 878, 879, 880, 881, 882, 555]. Primary alcohols [884] and aldehydes [749, 868, 555] are converted into carboxylic acids, secondary alcohols into ketones [749, 839, 844, 863, 865, 886, 887], ketones into keto acids [555, 559, 590] or acids [559, 597], ethers into esters [555], and amines into amides [854, 555] or imines [557], Aromatic amines are oxidized to nitro compounds [755, 559, 592], aliphatic nitro compounds to ketones [562, 567], sulfides to sulfones [846], selenides to selenones [525], and iodo compounds to iodoso compounds [595]. 

In addition to heterocycles that were successfully arylated under first-generation procedure, the reaction scope is broadened to include bis(aryl)imidazoles and triazoles, but benzothiazole was found to be incompatible. As previously observed, 3,4-dihydroquinazoline is a reactive coupling partner but only the dehydrogenated product 2-arylquinazoline is obtained. Furthermore, in addition to iodoarenes, bro-moarenes are reactive under these reaction conditions. The reaction is tolerant of a large number of functional groups and haloarene substituents, including nitrile, chloro, primary amide, ketone, and ester. Both electron-poor and electron-rich bro-moarenes showed good reactivity. Both para- and meta-substituents were well tolerated, but ortao-substituents (OMe, CF3) shut down the reaction. 

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