Mechanisms allylic amination

For the synthesis of protected allylic amines, a variety of synthetically useful carbamates and sulfonamides can be used, added to conjugated dienes [65]. Scheme 8.7 shows the proposed mechanism for these reactions. 

Allylic amide isomerization, 117 Allylic amine isomerization ab initio calculations, 110 catalytic cycle, 104 cobalt-catalyzed, 98 double-bond migration, 104 isotope-labeling experiments, 103 kinetics, 103 mechanism, 103 model system, 110 NMR study, 104 rhodium-catalyzed, 9, 98 Allylnickel halides, 170 Allylpalladium intermediates, 193 Allylsilane protodesilylation, 305 Aluminum, chiral catalysts, 216, 234, 310 Amide dimers, NMR spectra, 282, 284 Amines ... 

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. 

Scheme 3.36 Proposed mechanism of the allylic amination according to Johannsen and Jorgensen [128b, 131].

Like the synthesis of L-DOPA by asymmetric hydrogenation, the manufacture of L-menthol hy Takasago Company is also one of the early examples of an industrial process where asymmetric isomerization is a key step. The desired isomerization reaction is one of the steps of the overall synthetic scheme. The synthesis of L-menthol from diethyl geranylamine is shown by 9.2. The formal electron pair pushing mechanism for the isomerization of the allylic amine to the enamine proceeds according to reaction 9.3. 

Metal rf-inline complexes with various transition metals [1-10] and lanthanides [11,12] are well known in the literature. Early transition metal if-imine complexes have attracted attention as a-amino carbanion equivalents. Zirconium rf-imine complexes, or zirconaaziridines (the names describe different resonance structures), are readily accessible and have been applied in organic synthesis in view of the umpolung [13] of their carbons whereas imines readily react with nucleophiles, zirconaaziridines undergo the insertion of electrophilic reagents. Accessible compounds include heterocycles and nitrogen-containing products such as allylic amines, diamines, amino alcohols, amino amides, amino am-idines, and amino acid esters. Asymmetric syntheses of allylic amines and a-amino acid esters have even been carried out. The mechanism of such transformations has implications not only for imine complexes, but also for the related aldehyde and ketone complexes [14-16]. The synthesis and properties of zirconaaziridines and their applications toward organic transformations will be discussed in this chapter. 

The mechanism of the Petasis boronic acid-Mannich reaction is not fully understood. In the first step of the reaction, upon mixing the carbonyl and the amine components, three possible products can form iminium salt A, diamine B, and a-hydroxy amine C. It was shown that preformed iminium salts do not react with boronic acids. This observation suggests that the reaction does not go through intermediate A. Both intermediate B and C can promote the formation of the product. Most likely, the reaction proceeds through intermediate C, where the hydroxyl group attacks the electrophilic boron leading to an ate -complex. Subsequent vinyl transfer provides the allylic amine along with the boronic acid sideproduct. 

The cycHc urea moiety provides structural rigidity as well as hydrogen-bonding possibihties similar to those of the imidazoles described above. The corresponding 2-imidazolones have been prepared on a soHd phase by tandem aminoacylation of a resin-bound allylic amine with an isocyanate followed by intramolecular Michael addition [73]. However, due to the paucity of data presented on the characterized compounds and the brief experimental procedure, this synthesis is not discussed in detail. Access to cyclic ureas or thioureas has also been obtained by reaction with carbonyl- or thiocarbonyldiimidazole through a cyclo-release mechanism [74—76]. 1,3-Dihydroimidazolones have been obtained by treatment of ureido acetals with TFA and subsequent conversion in an intramolecular cyclization via an N-acyliminium ion [77]. 

A final example of an allylic C-H animation process involves a mechanism that does not fall into the classification of either a Cu-bound nitrene or N-centered radical-type process. In this case, A-Boc-hydroxylamine serves as the nitrogen source and is converted to the acylnitroso species via a disproportionation mechanism facilitated by P(OEt)3 and CuBr [50]. Such compounds will react with olefin substrates through a thermal ene-like rearrangement to give A-Boc-A-hydroxy allylic amines. The Cu catalyst is not believed to play a specific role in the actual C-H oxidation event. 

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. 

The group of agents generally known as allyl amines[34] strictly includes only naftifine and terbinafine, but because butenafine and tolnaftate function by the same mechanism of action, they are included in this class and are shown in Figure 40.8. One can, of course, consider the benzyl group of butenafine to be bio-isosteric with the allyl group of naftifine and terbinafine. 

Tolnaftate, a much older drug, is chemically a thiocarbamate but has the same mechanism of action as the allyl amines. These drugs have a more limited spectrum of activity than the azoles and are effective only against dermatophytes. Therefore, they are employed in the treatment of fungal infections of the skin and nails (35). 

Krische and co-workers have investigated the tertiary phosphine-catalyzed regjospecific allylic amination of MBH acetates through a tandem 5n2 -5n2 mechanism by using phthalimide derivatives as nucleophiles. When (1 )-C1-MeO-BIPHEP was used as a catalyst, the MBH adduct obtained from p-nitrobenzaldehyde and methyl acrylate reacted with phthalimide to give the allylic substituted product 297 in 80% yield with 56% ee (Scheme 3.126). ... 

Scheme 15.35 Mechanism of the palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement of tertiary amines.

SCHEME 11.34. Mechanism and activation mode for allylic amination of MBH acetates and carbonates. 

It was suggested that in the photochemically triggered oxidation of phenol by Ru(bpy)3, the proton charge was delocalized over a primary shell of water molecules firmly bound to the pyridinium cation.The tetra-2-oxypyridinate ruthenium(II, III) dimer [Ru2(hp)4Cl] and related diruthenium adducts were effective catalyst for the oxidation of allylic and benzylic C—H bonds. The bis(homoallylic) sulfamate esters were converted to the corresponding allylic amines using PhI(02C Bu)2 in CH2CI2. Both computational and experimental studies favoured a stepwise mechanism involving H atom abstraction/radical recombination and the intermediacy of a discrete short-lived diradical species. ... 

The base-induced rearrangement of aziridines has been examined using a combination of calculations and experiments. The calculations show that the substituent on nitrogen is a critical feature that greatly affects the favourability of both a-deprotonation and /3-elimination to form an allylic amine. Af-tosyl aziridines were found to deprotonate on the tosyl group, preventing further reaction. A variety of A-benzenesulfonyl aziridines having both a- and /3-protons decomposed when treated with lithium diisopropylamide (LDA) in various solvents have been reported. However, when a-protons were not present, allylic amine was formed, presumably via an 5 2-like mechanism. 

In 2004, Krische and colleagues demonstrated that exposure of Morita-Baylis-Hillman acetates to tertiary phosphine catalysts in the presence of 4,5-dichlorophthalimide enabled regiospecific allylic substitution through a tandem Sn2 -Sn2 mechanism. Through the use of the chiral phosphine catalyst, (i )-Cl-MeO-BIPHEP, the racemic Morita-Baylis-Hillman acetate depicted in Scheme 2.108 was converted into the corresponding enantiomerically enriched allylic amination product, thus establishing the feasibility of DKR. 

Duchene and Parrain developed a one-pot allylic amina-tion/palladium-catalyzed Sonogashira cross-coupling and heterocyclization process for the preparation of 1,2,4-trisub-stituted and 1,3-disubstituted pyrroles starting from diiodo-butenoic acid, a primary amine, and a terminal alkyne [49], Scheme 3.27 shows a plausible mechanism for this transformation. The initial C—N allylic amination, followed by a Sonogashira cross-coupling and an intramolecular hydroam-ination, affords a dihydroexoalkylidene pyrrole XIX, which rearranges into pyrrole 39. The reaction is influenced by the... 

---