Aromatic amines hydroamination

The formation of a bis(guanidinate)-supported titanium imido complex has been achieved in different ways, two of which are illustrated in Scheme 90. The product is an effective catalyst for the hydroamination of alkynes (cf. Section V.B). It also undergoes clean exchange reactions with other aromatic amines to afford new imide complexes such as [Me2NC(NPr )2]2Ti = NC6F5. ... 

The first example of acid catalysis appeared in a 1934 patent in which it is claimed that surface catalysts, particularly hydrosilicates of large surface area , known at that time under the trade name Tonsil, Franconit, Granisol, etc. lead to a smooth addition of the olefine to the molecule of the primary aromatic amine . Aniline and cyclohexene were reacted over Tonsil at 230-240°C to give, inter alia, the hydroamination product, N-cyclohexylaniline [47]. 

Under the same conditions, the hydroamination of acetylene with primary or secondary aromatic amines brings about the formation of dimerization-cyclization products since the generated imines or enamines, respectively, are not stable. 

Subshtuted 3-alken-l-ynes can be hydroaminated with primary or secondary aliphahc or aromatic amines at the alkynyl sites or at the alkynyl and at the alkenyl sites in the presence of Hg(ll) salts. However, the reachon is essentially stoichiometric in nature, even if the mercury compound can be recycled without apparent loss of achvity [262-264]. 

Very recently, Genet and Michelet developed a diastereoselective reaction that took place by hydroamination of an unactivated alkene followed by a cydization process under very mild conditions. This 1,6-enyne reaction was compatible with electron-poor aromatic amines, including amines bearing chloride atoms (Equation 8.73), which is very useful for further functionalization of the substituted aniline ring [164]. 

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

The diastereoselective addition of aniline to norbornene was accomplished using a catalytic amount of iridium(I). As the intermediate azametallacyclobutane 2 could be isolated its stereochemistry was determined by X-ray analysis both iridium and nitrogen occupy the exo position41. However, the scope of the amination method, with respect to the nature of the amine and the structure of the alkene, was not determined. Conversely, the analogous rhodium(I)-cat-alyzed reactions of norbornene and aromatic amines gave mixtures of hydroamination and hydroarylation products106. 

Che has reported the tandem hydroamination/hydroarylation of aromatic amines wirh terminal alkynes to form dihydroquinolines in which 1 equiv of aniline combines with 2 equiv of alkyne [23]. For example, reaction of 3-methoxyanilme with pheny-lacetylene (5 equiv) and a catalytic 1 1 mixture of the gold(I) N-heterocydic carbene complex (IPr)AuCl (IPr= l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine) and AgOTf at 150 °C under microwave irradiation led to isolation of dihydroquinoline 21 in 82 % yield (Eq. (11.15)). Alternatively, reaction of o-acetylaniline with pheny-lacetylene catalyzed by a mixture of (IPr)AuCl and AgOTf at 150 °C led to isolation of the quinoline derivative 22 in 93% yield via incorporation of a single equivalent of alkyne (Eq. (11.16)). Arcadi has reported the gold(IlI)-catalyzed hydroamination/ hydroarylation of 2-alkynylanilines with a,p-enones to form C3-alkyl indoles [24]. As an example of this transformation, treatment of 2-(phenylethynyl)aniline with 4-phenyl-3-buten-2-one and a catalytic amount of sodium tetrachloroaurate dihydrate in ethanol at 30°C formed 1,2,3-trisubstituted indole 23 in 88% yield (Eq. (11.17)). 

The hydroamination of phenylacetylene with primary or secondary aromatic amines is also catalyzed by Tl(OAc)3 to give imines or enamines, respectively, in low to good yields (10-89%) with TOE up to 6 h [261]. 

Gallium The hydroamination products ArCH(NArR )CH3 have now been obtained from the reaction of alkynes ArC=CH with aromatic amines ArNHR, catalysed by GaCl3, followed by reduction of the imine intermediates ArC(NArR )=CH2 with LiAlH4. DFT calculations suggest that the key step proceeds as a Markovnikov-type iyn-addition of GaCl3 and the amine across the C=C bond. ... 

The simple lithium amide LiHMDS catalyzes the addition of aliphatic and (notably) aromatic amines to vinyl arenes [40]. The catalytic activity is increased by addition of TMEDA and the reaction can be carried out in bulk without additional solvent. More reactive primary aliphatic amines also form a bis-hydroamination product, although the formatiOTi of the latter may be suppressed by using an excess of amine (21). Less reactive aromatic amines and a- and p-substituted styrenes give the monohydroamination adducts selectively [40]. Other readily available alkali metal-based catalysts include NaH [166], t-BuOK [164, 167, 168] and CsOH [169]. 

The inteimolecular hydroamination of allenes is readily catalyzed by early transition metal complexes to yield imines. An addition of aromatic and ahphatic amines to aUene requires high reaction temperatures (90-135°C) and long reaction times (1-6 days) when mediated by zirconocene- [41] and tantalum-imido [178] catalysts. The more efficient titanium half-sandwich imido-amide complex 42 operates under significantly milder reaction conditions (27) [179], Because the metal-imido species are prone to dimerization, sterically more hindered aliphatic and aromatic amines are more reactive. Simple, sterically unencumbered aliphatic amines add to aUenes in the presence of the bis(amidate) titanium complex 43 (28), although higher reaction temperatures are required [180]. 

A number of actinide complexes have been investigated with respect to their catalytic activity in the intermolecular hydroamination of terminal alkynes with primary ahphatic and aromatic amines [98, 206-209]. Secondary amines generally do not react and the reaction is believed to proceed via an metal-imido species similar to that of group 4 metal complexes. The reaction of Cp 2UMc2 with sterically less-demanding aliphatic amines leads exclusively to the anti-Markovnikov adduct in form of the -imine (31) [207] however, sterically more demanding amines, e.g., t-BuNH2, result in exclusive alkyne dimerization. The ferrocene-diamido uranium complex 12 (Fig. 4) catalyzes the addition of aromatic amines very efficiently (32) [98]. 

The hydroamination of alkynes with primary and secondary ahphatic amines necessitates the use of higher amounts of catalyst (17%) and higher temperatures, and TOFs are low (<1 h ) [260]. With ahphatic and aromatic terminal alkynes and a 5-fold excess of primary aliphahc amines, the products are the corresponding imines (40-78% yield, TOF up to 0.3 h ). In contrast to the CujClj-catalyzed reaction of phenylacetylene and secondary ahphatic amines (Scheme 4-12), the HgClj-catalyzed reachon is fully regioselechve for the Markovnikov hydroamination products which do not evolve under the reachon condihons (Eq. 4.66) [260]. 

The first example of anti-Markovnikoff hydroamination of aromatic alkenes has been demonstrated with cationic rhodium complexes.170 A combination of [Rh(COD)2]+/2PPh3 in THF under reflux yields the N-H addition product as the minor species alongside that resulting from oxidative amination (Scheme 37). Hydrogenation products are also detected. 

The scope of the lanthanide-mediated, intramolecular amination/cyclization reaction has been determined for the formation of substituted quinolizidines, indolizidines, and pyrrolizidines,1046 as well as tricyclic and tetracyclic aromatic nitrogen heterocycles.1047 The amide derivative OT ro-[ethylene-bis(indenyl)]ytterbium(m) bis(trimethyl-silyl)amide catalyzes the hydroamination of primary olefins in excellent yields.701 A facile intramolecular hydroamination process catalyzed by [(C5H4SiMe3)2Nd(/r-Me)]2 has also been reported. The lanthanide-catalyzed hydroamination enables a rapid access to 10,1 l-dihydro-5//-dibenzo[tf,rf]cyclohepten-5,10-imines (Scheme 283).1048... 

The organoactinide complexes Cp 2AnR2 (An = Th, U R = Me, NHR R = alkyl) and the bridge complexes 3-6 were found to be excellent precatalysts for the intermolecular hydroamination of terminal aliphatic and aromatic alkynes in the presence of primary aliphatic amines to yield the corresponding imido compounds [56, 99]. The reactivity exhibited for the thorium complexes was different, depending on the alkynes, from that for organouranium complexes. 

Schafer found that the bulky bis(amidate) complex is an effective catalyst for intermolecular hydroamination of terminal alkyl alkynes with alkylamines, giving exclusively the anti-Markovnikov aldimine product [309]. The same titanium complexes can also be utilized in the hydroamination of substituted allenes in good yields (Scheme 14.132). Under the catalysis of an imidotitanium complex, the highly strained methylenecyclopropane can undergo hydroamination reaction with either aromatic or aliphatic amines, to give ring-opened imine products in good to excellent yields and chemoselectivities [310]. 

Furthermore, this follow-up study also illustrated the broad applicability of DMCs for the hydroamination of various substrate molecules [37]. Zn-Co-DMCs could catalyze the hydroamination reaction of both aromatic and aliphatic alkynes with aromatic as well as aliphatic amines, a rare trait in heterogeneous hydroamination catalysts. 

Halland et al. showed that the same o-alkynylhaloarene substrates used successfully by others to access indoles (Scheme 24.1, disconnection D-3) could be used to access 2//-indazole products (Scheme 24.19) [90]. The reaction proceeded via an initial regioselective intermolecular palladium-catalyzed amination using a mono-substituted hydrazine to generate an N,N -disubstituted hydrazine. Intramolecular hydroamination then forms a dihydroindazole intermediate such as 42. Isomerization to the aromatic 2//-indazole products occurred spontaneously under the reaction conditions. A variety of examples were reported, and good functional group tolerance was observed. 

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