Dehydrogenative amination/amidation

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. 

A variant on this structure, dioxyline, has much the same activity as the natural product but shows a better therapeutic ratio. Reduction of the oxime (113) from 3,4-dimethoxyphenyl-acetone (112) affords the veratrylamine homolog bearing a methyl group on the amine carbon atom (114). Acylation of this with 4-ethoxy-3-methoxyphenyl acetyl chloride gives the corresponding amide (115). Cyclization by means of phosphorus oxychloride followed by dehydrogenation over palladium yields dioxyline (116). ... 

Synthesis of 216, an analog of the amide alkaloids, starting with ketone 214 was performed by Ishii et al. (176) (Scheme 33). The initial step involved the formation of cis secondary amine 215, which on N-formylation and dehydrogenation led to 216. Under Bischler-Napieralski conditions 216 could be recyclized to chelirubine (217). 

Synthesis of secondary amides via the oxidative coupling (dehydrogenation) of primary alcohols R CH3(OH) and primary amines R (CH3)NH3 to the amides... 

Subsequent ring closure with ammonia, hydrogenation using PtO2/H2 or Pd-C/H2 [32], DCC/HOBt-mediated amidation with t-butyl amine, followed by dehydrogenation using benzeneseleninic anhydride or 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone (DDQ)/bis(trimethylsilyl)-trifluoroacetamide (BSTFA) [33] combination afforded 4. 

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]. 

Amination of pyridine on heating with sodium amide in refluxing xylene observed by Chichibabin and Zeide nearly 100 years ago [132] was probably the first successful example of amino-dehydrogenation in the series of Jt-deficient aromatic systems. However, rather drastic reaction conditions and a requirement for an appropriate oxidant for the classic Chichibabin amination did not stimulate chemists in earlier days to enter this field of substitutions [23, 133, 134], Later on, van der Plas with coworkers [11, 19-21, 29, 35, 39, 40, 88], Vorbruggen [26], Pozharskii, Gulevskaya, and Maes [34, 45, 46, 48, 67, 68, 71, 72], McGill and Rappa [23], Pagoria, Mitchell, and Shmidt [59, 61, 63], Lopyrev [65, 66], Katritzky [58], and many other researches [11, 21, 45, 55, 58-74] contributed to the field of Sn amination reactions. 

Secondary amines do not react under these conditions. Thus, heating dibenzylamine with 1-hexanol under the experimental conditions resulted in a quantitative yield of hexyl hexanoate (entry 6, Table 1.8). The scope of this method was extended to the bis-acylation processes with diamines. Upon refluxing a slight excess of a primary alcohol and catalyst 1 with diamines (500 equivalent relative to 1) in toluene under argon, bis-amides were produced in high yields (Table 1.9). The high selectivity of the dehydrogenative amidation reaction to primary amine functionalities enabled the direct bis-acylation of diethylenetriamine with 1-hexanol to provide the bis-amide in 88% yield without the need to protect the secondary amine functionality [14]. 

Table 1.9 Dehydrogenative coupling of di- and tri-amines with alcohols to form bis-amides, catalyzed by complex 8.

Notably, the potentially competing polyester formation [19] by dehydrogenative selfcoupling of diols was not observed under these conditions. This is probably because the intermediate aldehyde reacts preferentially with the amine, which is a better nucleophile than the alcohol, forming a hemiaminal intermediate [14] (rather than a hemiacetal [11]) followed hy its dehydrogenation to the amide (Schemes 1.6 and 1.11). In addition, it should he noted that complex 8 also catalyzes the formation of amides by coupling of esters with amines (Section 1.4.2) [15] hence, even if some ester (or oligoester) were to be initially formed, it would be converted to the polyamide. 

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