Oxidations benzylic amination

Direct oxidation of diphenylmethanes is of little practical value as color formers. In liquid sulfur dioxide, leuco diphenylmethane 12 (Scheme 2) undergoes hydride abstraction by triphenylcarbenium perchlorate at the benzylic amine position to form immonium ion7 13, whereas in acetonitrile... 

The electrochemical oxidation of amines to imines and nitriles typically utilize a chemical mediator. The use of both Al-oxyl radicals [12, 13] and halogens has been reported for this process [14]. For example, the conversion of benzyl amine (14a) into nitrile (15a) and aldehyde (16a) has been accomplished using the M-oxyl radical of a decahydroquinoline ring skeleton as the mediator (Scheme 5). The use of acetonitrile as the solvent for the reaction generated the nitrile product. The addition of water to the reaction stopped this process by hydrolyzing the imine generated. A high yield of the aldehyde was obtained. In the case of a secondary amine, the aqueous... 

FIGURE 9.18 Separation of 1, methyl benzyl amine 2, tartaric acid 3, diastereomer 4, drug candidate BMS-X 5, oxidation product and 6, vehicle polymers. Using a ES-PFP column (250 x 4. 6 mm with 5 p.m particles) with a mobile phase gradient starting with 95% modifier/5%C02 held for 25 minutes and ramped to 15%C02 for 5 minutes at 1.5mL/min, 311 K and 18.0 MPa modifier 43% H20/56% methanol). (Unpublished data from S. L. Phillips et al., unpublished data. With permission.)... 

Der bei der Oxidation des Laevoglucosans entstehende Dialdehyd laGt sich mit Nitromethan/Natriummethylat zu 3-Nitro-3-desoxy-l,6-anhy-drohexop3n anosen cyclisieren 2is) wahrend mit Nitromethan/Benzyl-amin 2,4-Bis-benzylamino-3-nitro-2,3,4-tridesoxy-D-idosan als Haupt-produkt (53%) entsteht isia). 

The oxidative behaviour of the acridinium carbocations 61 was also explored by the group of Lacour in the photoinduced electron transfer reaction [160]. In the amount of 2 mol%, the achiral hindered acridinium salt 61 catalyzed the aerobic photooxidation of the primary benzylic amine to benzylimine in the yield of 74% (Scheme 63). 

Some further examples of stereoselective deprotonation/alkylation reactions of tricarbonyl-chromium complexed (V-methyl tetrahydroisoquinolines have been reported27. Starting with the enantiomerically pure (35)-methyl tetrahydroisoquinoline reaction with hexacarbonyl-chromium led to a mixture of endo- (40%) and exo- (60%) complexes, which were deprotonated with butyllithium and subsequently methylated with iodomethane. In this way methylation occurred firstly at the 4- and secondly at the 1-position. In all cases, the methyl group entered anti to the chromium complexed face. After separation of the alkylated complexes by chromatography and oxidative decomplexation, the enantiomerically pure diastereomers (—)-(l 5,35,47 )-and ( + )-(17 ,35,45)-1,2,3,4-tetrahydro-l,2,3,4-tetramethylisoquinolme were obtained, benzylic amines such as tetrahydroisoquinoline to 2-amino-4,5-dihydrooxazoles. Deprotona... 

Alkenes bound to cross-linked polystyrene can be epoxidized under conditions similar to those used in solution. The most commonly used reagent is m-chloroperbenzoic acid in DCM, but other reagents have also been used (Table 15.1). Because excess oxidant is usually required to furnish clean products, care must be taken with linkers or other functional groups prone to oxidation (ketones, amines, benzyl ethers, etc.). 

Transformation of alkylcatecholborane intermediates, thus formed after asymmetric hydroboration prior to oxidation, to the corresponding optically active amines with retention of configuration provides a very useful synthetic method. In fact, this process was realized through the reaction of an alkylcatecholborane with Grignard reagent and HNfOSO H, for example, benzylic amine 159, was obtained from 158 in 56% yield with retention of configuration [92] (Scheme 2.16). 

Benzylic amine containing compounds are particularly susceptible to autoxidation with subsequent hydrolysis such reaction often occur during stress testing using radical initiators. These compounds readily oxidize to the corresponding imine, which subsequently undergo hydrolysis to the primary amine and aldehyde derivatives. 

Cu(BF4)2.xH20 catalyses the ring opening of styrene oxide by amines under solvent-free conditions.22 Primary aromatic amines react regiospeciflcally at the benzyl carbon... 

Oxidation. Benzylic secondary amines are oxidized in high yield by dimethyldioxirane to nitrones,1 probably via hydroxylamines.2... 

Cr3+ can also be integrated into the structures of layered double hydroxides. A mixed oxide, prepared by calcination of ZnCr-LDH-CCh, was used in combination with t-BuOOH for the ketonization of alkyl and of benzyl pyridines and for the oxidation of benzyl amines to give Schiff bases (67,68). In contrast to MgAl-LDHs, for example, these materials display hardly any basicity so that base-catalyzed side reactions such as aldol condensations are avoided. 

In 2001, Itoh and coworkers reexplored the mechanism of ortAo-phenol hydroxylations using [ Cu°(L ) 2(02)] " (7, Figure 10). This complex contains a deutero-benzyl-amine moiety, and can undergo hgand auto-oxidation, forming benzaldehyde, through a proton-coupled electron transfer (PCET) reaction with the peroxo ligand. 

Whereas metal hydride is eliminated from the o--complex intermediates (cf. 309) in Chichibabin aminations, which results in the subsequent reaction of the metal hydride with ammonia or amines and the evolution of hydrogen, the o--complex intermediates can also be oxidized to the corresponding amino-N-heterocycles. Thus, 5-azacinnoline (320) can be aminated with primary and secondary aliphatic or benzyl amines in the presence of potassium hydroxide/potassium ferricyanide to give the corresponding amino derivatives 321 in up to 65% yield. The... 

In the oxidation of benzylamines, apart from formation of the dealkylated amine and benzaldehyde [61-64], formation of imines [65, 66], benzonitrile [64], diazines [62] anilines [67], and iV-benzylidene benzyl amines [64, 66, 67] has also been observed. 

Primary aliphatic amines can be oxidized to aldehydes or ketones. Other reagents used have been V-bromoacetamide (for benzylic amines), 3,5-di-tert-butyl-l,2-benzoquinone, and aqueous NaOCl with phase-transfer catalysts. Benzylic amine salts PhCHRNRj H" " Cl (R,R = H or alkyl) give benzal-dehydes or aryl ketones when heated in DMSO. Several indirect methods for achieving the conversion RR CHNH2 RR C=0 (R = alkyl, aryl, or H) have been reported. ... 

In addition, manganese oxide oxidizes benzylic methyl or methylene to carbonyl [814] and cleaves the carbon bonds of vicinal diols [577, 522]. It converts amines into imines [577, 525] tertiary amines into secondary amines [572], formamides [526, 527, 525], or ketones aromatic primary amines [575, 525] and hydrazo compounds [525] into azo compounds hy-droxylamines into nitroso [576] or nitro compounds [525] hydrazones into diazo compounds [520] phosphines into phosphine oxides [575] thiols into disulfides [576] and sulfides into sulfoxides [541]. 

The Cr-PILC catalyzed benzylic and allylic oxidations also provide a facile approach to the oxidative deprotection of allyl and benzyl ethers and amines. Treatment of allyl or benzyl ethers with one equivalent of tert-butyl hydroperoxide in the presence of Cr-PILC at room temperature resulted in the oxidative cleavage of the allyl- or benzyl-oxygen bond to give the alcohol but when two equivalents of tert-butyl hydroperoxide (TBHP) were used, the alcohol was oxidized further to the aldehyde or ketone (Eqn. 21.21).47 Oxidation of allyl amines resulted in the cleavage of the allyl-nitrogen bond to give the des-allyl amine.47 Benzyl amines, however, were oxidized to the benzamides (Eqn. 21.22).45... 

A remarkably efficient FeCl2-catalyzed intermolecular amination of simple benzylic substrates has been described (Fig. 15) [76]. These same authors have also noted the ability of CuBr to operate in a similar capacity [77]. iV-Bromosucci-mide (NBS) is used as the oxidant together with either a carboxamide or sulfonamide starting material. The /V-brominated amide purportedly reacts with FeCF to generate an Fe nitrene species that is capable of oxidizing benzylic C-H bonds, though evidence for such a mechanism is absent from the discussion. If a nitrenoid pathway is indeed operative, one might expect isocyanate formation to compete... 

Arylazides will decompose in the presence of [Co(TPP)] and unsaturated hydrocarbons to generate both aziridine and allylic amine product mixtures [88-90], Such a process is capable of oxidizing benzylic C-H bonds as well, though poor catalytic efficiency and problems with product over-oxidation limit the utility of these reactions [91, 92], Detailed kinetics analysis and Hammett studies have led Cenini and coworkers to propose a mechanism that does not involve a Co imido complex, as had been previously suggested. The observation of a Co(III) species by UV/vis spectroscopy strongly implicates a one-electron pathway for this particular amination method. 

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