Allylic amines hydroamination

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. 

Intramolecular hydroamination of cyclohexa-2,5-dienes has afforded the corresponding bicyclic allylic amines with high selectivity (Scheme 13).80 The reaction does not proceed through a direct hydroamination of one of the diastereotopic alkenes but more likely involves a diastereoselective protonation of a pentadienyl anion, followed by addition of a lithium amide across the double bond of the resulting 1,3-diene and a highly regioselective protonation of the final allylic anion. 

The Bi(OTf)3-Cu(CH3CN)4PF6 system has been reported to promote efficiently an intermolecular 1 1 hydroamination of 1,3-dienes R1CH=CHCH=CHR2 with various carbamates, sulfonamides, and carboxamides to afford allylic amines in Markovnikov... 

Intramolecular hydroamination of cyclohexa-2,5-dienes (204) mediated by Bu"Li has been reported to produce the corresponding bicyclic allylic amines (205) with high... 

Several catalytic systems have been investigated for hydroamination of unsaturated bonds [16]. Takahashi et al. reported the telomerization of 1,3-dienes in the presence of an amine leading to octadienylamine or allylic amines when palladium catalysts are used in association with monodentate or bidentate phosphine ligands, respectively [17]. Dieck et al. demonstrated the beneficial effect of addition of an amine hydroiodic salt in the hydroamination reaction of 1,3-dienes in which the allylic amines are produced via an intermediate Jt-allyl palladium complex [18]. Coulson reported the Pd-catalyzed addition of amines to allenes where dimerization is incorporated [4]. This reaction presumably proceeds via a cyclic palladium intermediate in which the Pd activates the olefinic bond for nucleophilic attack the reactions are therefore different from pronucleophilic additions. 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

The direct catalytic reaction of nucleophiles such as amines with 1,3-dienes to give allylic amines is difficult to achieve. A high-throughput assay was used to screen catalysts for the 1 1 hydroamination of aniline to 1,3-cyclohexadiene (equation 44). ... 

The distal bond cleavage occurs in hydroamination. Reaction of MCP 208 with dibenzylamine afforded the allylic amine 209 by using the combination of 7r-allylpalladium chloride with DPPP as a catalyst [61]. Similarly sulfonamide 211 was allylated with MCP 210 to produce the diallylated amide 212 using a complex mixture of Pd(0), Pd(II), and PPhs as a catalyst [62]. The use of Pd(0)-PPh3 in an appropriate ratio seems to be effective. 

Phenyl-1-propyne (55) underwent facile formal intermolecular hydroamination, affording the allylic amine 56 in high yield at 0 "C in the presence of AcOH or benzoic acid. In this reaction, at first, Pd-catalyzed isomerization of 55 to pheny-lallene (57) occurs by addition-elimination of H-Pd-OAc to internal alkyne 55, and then the allene 57 is converted to jr-allylpalladium intermediate 58 by hydropal-ladation. The final step is a well-known amination to produce the allylic amine 56. As an intramolecular version, 2-(2-phenylpropenyl)pyrrole (60) was obtained from l-phenyl-7-amino-l-hexyne 59 [16,16a]. Similarly Pd/benzoic acid-catalyzed hydroalkoxylation of 55 with (—)-menthol (61) afforded the allylic ether 62 [17]. 

Following early studies of the nickel-catalyzed coupling of dienes with amines to generate mixtures of 1 1 and 2 1 adducts a high-throughput colorimetric assay discovered that the catalyst derived from Ni(cod)2 and dppf efficiently catalyzes the 1 1 hydroamination of 1,3-dienes with primary or secondary amines to produce allylic amine products (Scheme 3-107). A catalytic quantity of trifluoroacetic acid was a key component in the optimized procedure. 

A catalytic tethering that employs a simple aldehyde as catalyst has been reported to facilitate hydroamination of allylic amines (116) at room temperature to produce vicinal aminohydroxyamines (118). The reaction proceeds via formation of the mixed aminal (117) from the amine, aldehyde, and hydroxylamine, resulting in a facile intramolecular hydroamination event. With chiral aldehydes, enantioselectivities up to 87% ee were attained. ... 

The hydroamination of 1,3-dienes has been known for many years, but these reactions have often generated mixtures of products. More recently, the intermolecular and intramolecular hydroamination of dienes has been reported with lanthanide and palladium catalysts to generate allylic amines in high yields. These reactions have also occurred with high enantioselectivity in some cases. 

Yamamoto has also demonstrated the intermolecular hydroamination of mono-substituted arylallenes with morpholine [40]. For example, treatment of l-p-tolyl-1,2-propadiene with morpholine and a catalytic 1 1 mixture of [PPh2(o-tolyl)]AuCl and AgOTf in toluene at 80 °C for 24h led to isolation of the allylic amine 56 in 83% yield as a single regio- and stereo-isomer (Eq. (11.31)). 1-Alkylallenes, 1,1-, and 1,3-disubstituted allenes also underwent gold(I)hydroamination with morpholine, albeit with diminished efficiency and/or regioselectivity. 

Oxidative addition of allylic amines to Ni(0) precursors in the presence of acid has been shown to lead to cationic (allyl)Ni complexes. Thus, Ni(cod)(dppf) reacts with a range of cyclic allylic amines in the presence of trifluoroacetic acid (TFA) to generate complexes 74, as shown in Scheme 22. " This process can proceed by protonation of the amine and the oxidative addition of the resulting ammonium salts, as above. The same system or a mixture of Ni(cod)2 and dppf catalyzes the hydroamination of dienes. In this case, the catalysis is thought to proceed via the initial protonation of Ni(0) precursor to give an Ni-H species that undergoes insertion of the diene to generate an allyl... 

Mild and selective 1 1 reactions of amines with 1,3-dienes without telomer-ization are still limited. The recently reported bismuth-catalyzed intermolecular hydroamination with various amides (carbamates, sulfonamides, and carboxamides) to produce allylic amines in good yields is a good example of such a reaction (Equation 56 and Scheme 11.4) [80]. Some additives are necessary to optimize the reaction conditions. Cyclic and acyclic dienes were tested. The isomer ratio (1,2-adduct versus 1,4-adduct) depended on the nature of the dienes. 

Dienes were also subjected to the hydroamination reaction in the presence of Pd catalysts such as the 1. A colorimetric assay showed that among various catalysts, complex formed from [Pd( j -allyl)Cl]2 and PPh3 is the most active. The pyridyl derivative is obtained in 88% yield (eq 94). The enantioselective addition was also optimized for allylic amine formation in good yield and 95% enantiomeric excess. Furthermore a range of arylamines could react with cyclohexadiene in 86-95% ee and 59-83% yield (eq95). 

The allylpalladium chloride dimer (1) has served as an excellent precursor of active catalyst for hydroamination of various substrates such as methylenecyclopropanes, enynes, and dienes. The reaction of (4-phenylbutylidene)cyclopropane with amines in the presence of 5 mol % of dimer (1) and dppp, (l,3-bis(diphenylphos-phino)propane), gave the corresponding allylic amine in 31-91% yield (eq 92). It is noteworthy that Pd precursors such as Pd2(dba)3 CHCl3, Pd(PPh3)4, or PdCl2(PPh3)2 were less efficient Pd(OAc)2 did not promote the reaction. 

A kinetic study of intermolecular hydroamination of allylic amines by N-alkylhydroxylamines has revealed a first-order dependence on aldehyde catalyst. 

Chen K (2011) Application of palladacycles in asymmetric hydrophosphinations, asymmetric hydroamination and tandem allylic aminations/aza-Cope rearrangements. PhD Dissertation, Nanayang Technological University... 

Ruthenium complexes mediate the hydroamination of ethylene with pyridine.589 The reaction, however, is not catalytic, because of strong complexation of the amine to metal sites. Iridium complexes with chiral diphosphine ligands and a small amount of fluoride cocatalyst are effective in inducing asymmetric alkene hydroamination reaction of norbomene with aniline [the best enantiomeric excess (ee) values exceed 90%].590 Strained methylenecyclopropanes react with ring opening to yield isomeric allylic enamines 591... 

Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

Transition metal-benzyl complexes also react readily with nucleophiles, but the origin of this enhanced reactivity results from effects other than the typical rapid rate of nucleophilic attack at an electrophilic benzyUc carbon. As shown in Equation 11.17, benzyl groups can be bound in an fashion, much like an aUyl group. As presented later in this chapter, cationic iq -allyl complexes react with a variety of nucleophiles. iq -Benzyl groups are common in the chemistry of palladium(II), - and these ti -benzyl and phen-ethyl complexes react with a variety of nucleophiles. For example, these complexes react with malonate anions, and they have been shown to react with amines " during some recently developed hydroamination processes. These reactions occur with predominant inversion of configuration. ... 

Lanthanide complexes also catalyze the hydroamination of 13-dienes. The lanthanide catalysts originally developed for the intramolecular hydroamination of aminoalkenes are particularly active for the intramolecular additions of alkyl amines to dienes. The scope of this process is broad an illustrative example showing the high diastereoselectiv-ity of the cyclization of a chiral amine is shown in Equation 16.82. These reactions occur by insertion of the diene into a lanthanide-amide intermediate to form an allyl-metal intermediate. 

The hydroamination of olefins has been shown to occur by the sequence of oxidative addition, migratory insertion, and reductive elimination in only one case. Because amines are nucleophilic, pathways are available for the additions of amines to olefins and alkynes that are unavailable for the additions of HCN, silanes, and boranes. For example, hydroaminations catalyzed by late transition metals are thought to occur in many cases by nucleophilic attack on coordinated alkenes and alkynes or by nucleophilic attack on ir-allyl, iT-benzyl, or TT-arene complexes. Hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of an olefin into a metal-amide bond. Finally, hydroamination catalyzed by dP group 4 metals have been shown to occur through imido complexes. In this case, a [2+2] cycloaddition forms the C-N bond, and protonolysis of the resulting metallacycle releases the organic product. 

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