Oxidative Allylic Aminations

3-dimethylbutadiene 34 was heated with nitrosobenzene 32 in dioxane, a smooth hetero-Diels-Alder reaction to derivative 35 occurred (A). However, when the same mixture was heated with hydroxylamine 29a in the presence of FeCl2/FeCl3, only allylic amines 30a and 36 were obtained in 24% and 20% yield, respectively. No trace of hetero-Diels-Alder product 35 was found. 

The electronic properties of the nitroarene strongly influence the reactivity. Whereas nitrobenzene 38a gave the amination product 30a in high yield, electron-withdrawing substituents decreased the yield. With 4-methoxynitrobenzene 38d, almost no product 30d was isolated. 

In order to reduce the reaction temperature and CO pressure necessary for the allylic animation with nitrobenzene 38a in the presence of [Cp Fe(CO)2]2, Nicholas and coworkers developed a photochemically assisted method, that requires only 3-6 atm CO and 80-120 °C to produce the allylic amines in reasonable yields [138]. 

The allylic amines 30e and 31d were obtained in 87% and 75% yield, respectively. N-Alkylation and subsequent treatment with methylamine-40% water or pure butylamine gave the corresponding N-methyl-N-allylamine 42 and 43 in good overall yield. 

From the discussion above, the following conclusions can be drawn. Apart from some selected examples, the issue ofchemoselectivity and catalytic activity in iron-catalyzed allylic hydroxylation has not so far been solved. In particular, synthetically useful methods with a broad scope concerning alkene substrates are still lacking. Furthermore, in many cases it seems to be difficult to avoid overoxidation of the allylic alcohol to the corresponding enone. In addition, most published procedures utilize the alkene in a large excess (often as a solvent), thus limiting the use of functionalized alkenes which are not commercially available. 

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Very recently, Liu and coworkers reported a palladium-catalyzed intramolecular aerobic oxidative allylic amination of unactivated alkenes [34]. The reaction of 22... 

Shimizu Y, Obora Y, Ishii Y (2010) Intermolecular aerobic oxidative allylic amination of simple alkenes with diarylamines catalyzed by the Pd(OCOCF3)2/NPMoV/02 system. Org Lett 12(6) 1372-1374... 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

The first of the nudeophilic ring-opening reactions of vinylaziridines discussed in this section is diborane reduction, developed by Laurent and coworkers in 1976 (Scheme 2.24). Treatment of N-unsubstituted vinylaziridines 89 with B2H6 gives allyl amines 92 by SN2 reduction via cyclic intermediates 90 [40]. In contrast, treatment with 9-BBN gives 2-(hydroxyethyl)aziridines 93 after oxidative workup (Scheme 2.25) [41]. 

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

Transition metal complex-catalyzed carbon-nitrogen bond formations have been developed as fundamentally important reactions. This chapter highlights the allylic amination and its asymmetric version as well as all other possible aminations such as crosscoupling reactions, oxidative addition-/3-elimination, and hydroamination, except for nitrene reactions. This chapter has been organized according to the different types of reactions and references to literature from 1993 to 2004 have been used. 

Oxidative phenolic coupling. Biosynthesis of the alkaloid narwedine (3) is known to involve oxidative phenolic coupling of norbelladine derivatives (1), but the usual oxidants for such coupling in vitro convert 1(R = H) into the oxomaritidine skeleton (4) rather than 3. A new biomimetic synthesis of 3 involves the palladacycle 2, formed by reaction of 1(R = CH3) with Li2PdCl4, which is known to form complexes with allylic amines or sulfides (8,176-177). Oxidation of 2 with thallium(III) trifluoroacetate effects the desired coupling to give 3. 

Figure 2.5 Schematic representation of the Au/MPS/PAH-Os/solution interface modeled in Refs. [118-120] using the molecular theory for modified polyelectrolyte electrodes described in Section 2.5. The red arrows indicate the chemical equilibria considered by the theory. The redox polymer, PAH-Os (see Figure 2.4), is divided into the poly(allyl-amine) backbone (depicted as blue and light blue solid lines) and the pyridine-bipyridine osmium complexes. Each osmium complex is in redox equilibrium with the gold substrate and, dependingon its potential, can be in an oxidized Os(lll) (red spheres) or in a reduced Os(ll) (blue sphere) state. The allyl-amine units can be in a positively charged protonated state (plus signs on the polymer...

Scheme 10.8 outlines the application of rhodium-catalyzed allyhc amination to the preparation of (il)-homophenylalanine (J )-38, a component of numerous biologically active agents [36]. The enantiospecific rhodium-catalyzed allylic amination of (l )-35 with the lithium anion of N-benzyl-2-nitrobenzenesulfonamide furmshed aUylamine (R)-36 in 87% yield (2° 1° = 55 1 >99% cee) [37]. The N-2-nitrobenzenesulfonamide was employed to facilitate its removal under mild reaction conditions. Hence, oxidative cleavage of the alkene (R)-36 followed by deprotection furnished the amino ester R)-37 [37, 38]. Hydrogenation of the hydrochloride salt of (l )-37 followed by acid-catalyzed hydrolysis of the ester afforded (i )-homophenylalanine (R)-3S in 97% overall yield. 

Among the first reported synthetic methods for alkene isosteres, a sigmatropic rearrangement of oxidatively activated allylic selenides to provide Boc-protected allylic amines was used for the synthesis of the D,L-Tyn i[is, CH=CH]Gly isostereJ711 The method resulted in a racemic dipeptide isostere, and only a Gly residue at the C-terminus is possible. It is no longer competitive compared with more recent methods using rearrangement of allylic tri-chloroacetimidates. 

Another means of producing Michael acceptors is by the oxidation of unsaturated amines of alcohols, such as allyl amine (equation 9.16). 

Conjugated dienes afford either allylic amines or saturated diamines (equation 159).204,219 When mer-cury(II) oxide plus tetrafluoroboric acid is employed, dihydropyrroles are formed instead (equation 160).220... 

Ab Initio MO calculations of a model complex Rh(PH3)2(NH3)(CH2=CHCH2NH2) were earned out to shed light to the detailed mechanism of Rh(l)-catalyzed isomerization of allylic amines to enamines.5 This study suggests that the square-planar [RhiPHjyNHjXCf CHCHjNHj) complex is transformed to [Rh(PH3)2(NH3)(( )-CH3CH=CHNH2)]+ via intramolecular oxidative addition of the C(l)-H bond to the Rh(I) center, giving a distorted-octahedral Rh(lll) hydride intermediate, followed by reductive elimination accompanied by allylic transposition. 

An alternative approach to the oxidation of alcohols to ketones was also reported by Shea et al., who incorporated a nitroxide catalyst into a polymeric matrix [56], A polymerisable 2,2,6,6-tetramethylpiperidine (90) was derivatised as /V-allyl-amine (91), which was removed after polymerisation, leaving a catalytically active nitroxide (92) able to form stable free radicals, thereby efficiently catalysing the reaction of oxidation with yields ranging from 55 to 88%. 

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