Arylation of imines

So far, there is only one report describing the use of chiral NHC-metal complexes in catalytic asymmetric arylation of imines. This was achieved by using C -symmetric cationic NHC-Pd diaquo complex 20 (Scheme 7.6) [38]. The arylation of a variety of A-tosylimines with different arylboronic acids was carried out under mild conditions. The presence of electron-withdrawing or electron-donating substituents on both partners did not seem to affect the reaction and the corresponding chiral diarylamines were obtained in good to excellent yields and high enantiomeric excess. 

Figure 85 Examples of chiral ligands used for the alkylation and arylation of imines by diorganozinc reagents.

Synthesis of diarylmethylamine derivatives, Ar1 -CH( Ar2 )-NHS02-C(dl4-p-N02, has been achieved enantioselectively using rhodium-catalysed arylation of imines with arylboroxines.56... 

Table 2. Synthesis of fluorenones via 1,4-palladium migration and subsequent arylation of imines.

Rhodium Phosphine-Catalyzed Arylation of Imines The asymmetric rho... 

The mechanism of the rhodium catalyzed arylation of imines presumably occurs via an initial transmetallation to produce the arylrhodium species 59 (Figure 1.10). Aryl transfer followed by a second rhodium boron transmetallation (or protonation by water) completes the catalytic cycle. 

Rhodium Diene-Catalyzed Arylation of Imines Hayashi has shown that the asymmetric synthesis of diarylmethylamines could be realized with high enantio control by the rhodium catalyzed arylboronic acid addition to N tosyl imines [119]. Ihe rhodium catalyst bears the C2 symmetrical bicyclo 2.2.1]heptadicne ligand 54. 

This protocol also proved applicable to directed arylations of imines [73], imidazolines, oxazolines (Scheme 19) [74, 75], as well as further arylazoles [76] as pronucleophilic starting materials. The use of 2-oxazolinyl moieties as DG is particularly noteworthy, since they can be easily converted into a variety of valuable functionalities [77],... 

Scheme 32 Proposed catalytic cycle for the directed C-H arylation of imines with NaBPh4 [123]...

Arylation reactions of aromatic ketimines were developed, and in many cases the products of the reaction were isolated after subsequent hydrolysis. Therefore, these arylations constitute an indirect method for the preparation of arylated aromatic ketones, the direct functionalizations of which are often more difficult. Thus, direct arylation of imine 42 with sodium tetraphenylborate catalyzed by [RhCl(cod)]2 afforded a mixture of mono- and diarylated benzophenone imines (44 and 45) (Scheme 9.16) [53]. The formation of the corresponding amine 46 clearly indicated that 42 also acted as a hydride acceptor in this transformation. Most likely, the reaction occurs via initial coordination by the benzophenone imine to a phenylrho-dium intermediate followed by orfho-rhodation to afford the five-membered rhoda-cyde intermediate 47 (Scheme 9.16). Subsequent reductive elimination generates the monophenylated product 44 and a rhodium hydride, which then reduces imine 42 in the presence of ammonium chloride as proton donor to regenerate the catalytically active speties. 

The arylation of imines can be applied to indole synthesis. The Fischer indole synthesis was carried out by Pd-catalyzed arylation of benzophenone hydrazone (69) to give A-arylbenzophenone hydrazone 70. The subsequent exchange reaction... 

Pioneering studies of the catalytic, enantioselective arylation of imines date back to 2000, when Hayashi disclosed a rhodium/phosphine-catalyzed addition of arylstannanes to N-tosylarylimines (31). Whereas, the method gave rise to highly enantioenriched diarylmethylamines, five equivalents of the stannane were required to obtain high yields. 

Scheme 8.14 Rhodium-catalyzed enantioselective arylation of imines 42.

Figure 8.4 Examined ligands in the rhodium-catalyzed arylation of imines.

Scheme 8.15 Rhodium-catalyzed diastereoselective arylation of imines 57.

Scheme 9.4 Rhodium-catalyzed direct arylation of imine 5 with boronate 6.

During studies on rhodium-catalyzed Suzuki-Miyaura cross-coupling reactions, Miura and coworkers reported more recently on the use of less-toxic tetraphenyl-borate 6 for the direct arylation of imines (Scheme 9.4) [16]. Unfortunately, rather low yields of mono- and di-arylated products were obtained, this being due to a reduction of the starting material via a sequence consisting of a rhodium hydride addition and subsequent protonation. The reduction of the imine is mandatory for the regeneration of a rhodium chloride species, and thereby for catalytic turnover. 

The same protocol proved appHcable to directed arylations of imines, imidazolines and oxazolines as pronucleophilic starting materials (Scheme 9.24) [33]. Transformations of the latter substrates should prove useful, since 2-oxazolinyl substituents can easily be converted into a variety of valuable functionaHties [34]. 

In this chapter that highlights the synthesis of arylamines, we will discuss the most recent and relevant developments in the catalytic arylations of imine substrates, which incidentally are mostly enantioselective. The application of organomet2Jlic cat2dysts bearing Pd, Rh, Ru, and other metal catalysts will be considered, as well as the recent multicomponent Petasis reaction. 

Direct additions of aryl groups to the C=N bond has been a popular method in the past [2a], although the poor electrophilicity of the azomethine carbon severely complicated this transformation, due to a tendency for the imine substrates and derivatives to undergo enolization. To circumscribe this problem, several arylating agents were studied, and it was in fact the pioneering studies of the catalytic enantioselective arylation of imines reported by Hayashi and coworkers that have led to the application of rhodium catalysts in this particular catalytic transformation. Their work dates back... 

Scheme 6.3 Proposed mechanism for the catalytic asymmetric arylation of imines catalyzed by a rhodium complex with a phenyltitanium reagent [6],...

Many reports concerning Rh-catalyzed asymmetric arylation of imine substrates were found [28], but as far as we are aware, there are very few reports on the application of other metals, notably, Pd for instance [29]. The reason behind poor application of this catalyst may rely on the fact that palladium(II) catalysts have a slight tendency to promote p-hydride elimination, giving a Heck-type... 

As far as we are aware, there have been no other reports on the arylation of imine substrates with ruthenium catalysts, besides our own work. In 2012, we published our efforts at developing a Ru-catalyzed asymmetric catalytic imine arylation with organoboron reagents and with chiral phosphane and new NHC-type ligands (Scheme 6.33) [44]. 

The addition of aryl groups to C=N bonds can be achieved using cooper-catalyzed asymmetric reactions with organometallic reagents. The addition of alkylzinc and related reactions is quite common in literature [47] whereas copper-catalyzed asymmetric arylation of imines is somewhat harder to find. We wish to report some successful examples of this type of catalysts. 

The Pd(0)-mediated a-arylation of esters is an efficient and versatile tool for the preparation of a-aryl carboxylic acids and a-aryl amino acids. Using areadily available catalyst system, e.g., Pd2(dba)3 dba and carbene precursor or t-Bu3P, many aryl halides and esters, in the presence of a strong base, react to form a series of ester-protected a-aryl carboxylic acids, e.g., 6a and 7a react to give 8a. A similar protocol facilitates the a-arylation of imine-protected glycinates with aryl halides to form ester-protected a-aryl amino acids. A useful example is the reaction of 6c and 7c to give 8c (eqs 9-11). 

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