Hydroamination of vinyl arenes

Table 6 Optimization of reaction conditions for hydroamination of vinyl arene 4a...

Table 7 Bi(OTf)3/Cu(CH3CN)4PF6-catalyzed intermolecular hydroamination of vinyl arenes...

Hydroamination of vinyl arenes is a more facile process, proceeding exclusively via 2,1 insertion (Fig. 21) [100] obviously resulting from an aryl-directing effect as discussed in Sect. 3.1. 

Scheme 11.2 Proposed mechanism for the palladium catalyzed hydroamination of vinyl arenes. 

The palladium catalyzed asymmetric hydroamination of cyclohexadiene with arylamines utilizing a variant of Trost s ligand R,R) 61 proceeds with high enantio selectivities under mild conditions (Scheme 11.19) [21]. The mechanism is believed to follow a similar pathway as proposed for palladium catalyzed hydroamination of vinyl arenes (Scheme 11.2) [17]. 

The intermolecular hydroamination is significantly less feasible than the intramolecular process as the C-C unsaturated moiety is not tethered in the vicinity of the catalytic center. The mechanism is believed to be analogous to the intramolecular case, with insertion being less favorable [20]. The insertion step was identified to be rate limiting in the intermolecular lithium-amide-catalyzed hydroamination of vinyl arenes by detailed DFT-analysis [40]. 

Fig. 12 Rare earth metal-catalyzed anti-Markovnikov hydroamination of vinyl arenes [20]...

Due to the high reactivity of vinyl arenes, a broader range of catalysts is available, including very robust and readily accessible compounds. Sodium metal readily catalyzes the hydroamination of styrene with secondary [156-160] or primary [161, 162] aliphatic amines at ambient or slightly elevated temperatures. The a/iri-Markovnikov addition of the amine moiety is favored (19) [160]. 

The well-defined copper complexes 94 and 95 (Fig. 2.16) have been used as catalysts for the intermolecular hydroamination of electron-deficient alkenes [Michael acceptors, X=CN, C(=0)Me, C(=0)(0Me)] and vinyl arenes substituted... 

The intramolecular anti-Markovnikov hydroamination of l-(3-aminopropyl)vinyl-arenes (71 R = H, Me, CH2OMe, CH2OTBS) in the presence of a rhodium catalyst to form 3-arylpiperidines (72) has been reported. In contrast to intermolecular hydroamination of vinylarenes, which occurs in high yields in the presence of rhodium catalysts... 

Two mechanistically plausible scenarios for nucleophilic attack on the q benzyl palladium species seem feasible. Formation of the C N bond could occur either via external attack of the amine through inversion of configuration at the carbon stereocenter, or alternatively the amine could coordinate to palladium followed by an internal attack on the q benzyl ligand. Mechanistic investigations [15] using stoi chiometric amounts ofthe enantio and diastereomerically pure q benzyl palladium complex [ (R) Tol BINAP [q 1 (2 naphthyl)ethyl Pd](OTf) (8) revealed that the re action with aniline produced predominantly (R) N1 (2 naphthyl)ethylaniline R) 9), consistent with external nucleophilic attack (Scheme 11.3) [15]. However, it was noted that the catalytic reaction of [ (1 ) Tol BINAP Pd(OTf)2] with vinyl arenes and amines produced preferentially the opposite enantiomeric (S) amine hydroamination... 

The range of amines involved may be expanded to more basic alkylamines (Eq. 11.5) [16]. Compound 10 was obtained in moderate yield and enantioselectivity utilizing the R,R) Et FerroTANE ligand. Note that almost stoichiometric amounts of a strong Bronsted acid are required to afford the Markovnikov hydroamination product of the vinyl arene. 

Multiple efficient catalysts were reported for the intramolecular process, while the intermolecular process has been studied predominantly for alkynes. The reactivity of the unsaturated fragment decreases in the order alkyne > allene diene > vinyl arene unactivated alkene with the intermolecular hydroamination of simple alkenes representing the most difficult transformation. The hydroamination of all types of carbon-carbon unsaturated fragments will be covered in this chapter. 

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]. 

A totally different approach for hydroamination of vinylarene is realized by intermediacy of Ti -arene metal complex, facilitating nucleophilic attack of amines at the vinyl linkage due to the electron-withdrawing effect of metal. This type of activation might be brought by the use of d metals, such as Cr°, Fe , and Ru which are relatively easy to form T] -arene complexes [51]. 

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