Hydroamination of styrenes

The first example of hydroamination of styrene in the presence of an alkali metal appeared in a patent in 1948, albeit with a low catalytic activity (Eq. 4.30) [149]. The anti-Markovnikov addition product was obtained. 

The n-BuLi-catalyzed hydroamination of styrene has been extended to 4-aryl-piperazines [157, 158]. For example, N-(4-fluorophenyl)piperazine reacts with styrene to afford the hydroamination product in 99% yield (Eq. 4.33). 

Figure 10 13C KIEs for catalysed hydroamination of styrene with aniline in benzene at 80°C.

Significant progress is being made in catalytic N-C bond formation. Thus, the stereoselective hydroamination of styrene derivatives [119] and norbomene [120] was achieved with BINAP catalysts (Pd and Ir, respectively) (cf. eq. (18)). 

Preparation of aliphatic amines by direct hydroamination of alkenes with amines is a highly desirable reaction. However, except for the well-established hydroamination of 1,3-dienes via 7r-allylpalladiums, no smooth hydroamination of simple alkenes is known. As a breakthrough, Kawatsura and Hartwig reported that the hydroamination of styrene derivatives with aniline is catalyzed by Pd(TFA)2 and DPPF in the presence of trifluoroacetic acid (TFA) or triflic acid as a cocatalyst to afford the branched amine 24 regioselectively in 99 % yield. Formation of the branched amine 24 offers an opportunity of asymmetric amination. They obtained the (5)-amine 25 in 80 % yield with 81 % ee using (/ )-BINAP as a chiral ligand [14]. The reaction is explained by insertion of styrene to the H-Pd bond and nucleophilic attack of amine on an fj -benzylpalladium complex [15]. Hii and coworkers obtained the amine 24 with 70 % ee in 75 % yield using the dicationic Pd complex, [Pd(MeCN)(H20)(/ -BINAP)](0Tf)2 [16]. 

Scheme 15.17 Ruthenium-catalyzed anti-Markovnikov hydroamination of styrene.

To get a better insight into this reactivity trend and to eventually determine the real abilities of large Ae elements, our group has developed three families of heteroleptic complexes supported by various monoanionic ancillary ligands—anilido-imino, LN (30—32), phenolate-amino-alkoxy (LO (33—36), and 8-diketiminate BDI (37—39)—and used them for the intermolecular hydroamination of styrene derivatives and isoprene (Scheme 28.8, Table 28.5) [27]. 

Scheme 28.8 Intennolecular hydroamination of styrene derivatives and isoprene with amines catalyzed by heteroleptic Ae complexes 30-39 [27],...

TABLE 28.5 Intermolecular Hydroamination of Styrene and Isoprene with Amines Catalyzed by Heteroleptic Ae Complexes [27] ... 

Kinetic studies of the hydroamination of styrene with pyrrolidine catalyzed by 32 revealed an empirical rate law V = [styrene] [pyrrolidine] °[32] °. A strong kinetic isotope effect was observed in the reaction of styrene with A-deuterated pyrrolidine catalyzed by 32 = 6.8 and 7.3 at 40 and 60 °C respectively). These results were conciliated... 

SCHEME 3.20 Iron-catalyzed Markovnikov hydroamination of styrenes [21]. 

As previously mentioned [155], PhNHj does not react with styrene under the above conditions. However, Beller et aL discovered that the hydroamination of styrene could be achieved in excellent yield by using either a n-BuLi-K2C03 mixture or, better, LBuOKas catalysts [159]. Using FBuOK (10%) in THF at 120°C (pressure tube), styrene is hydroaminated with aniline (5 equiv.) to give the anti-Markovnikov product in 96% yield (Eq. 4.34), R = = R = = H, TOF = 0.5 h ]. The scope of... 

Ruthenium A hydroamination of styrenes ArC(Me)=CH2 with amines, such as piperidine or morpholine, can be catalysed by cationic Ru complexes in combination with chiral diphosphines, for example, [(C6H6)RuCl2]2 and xylylBINAP. The reaction has been reported to be -selective and the products ArC H(Me)CH2NR2 were obtained with <76% ee. ... 

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]. 

Regioselective transformation was observed leading to the ) -adduct as a sole product. Involvement of the rr-allylic intermediate (similar to Pd-catalyzed hydroamination of styrene) in the catalytic cycle was excluded, since the a-adduct was not formed in Ph2P-H addition to styrene and vinyl pyridine [126]. The plausible catalytic cycle of alkenes hydrophosphination involves oxidative addition of the phosphine to Ni(0) leading to the formation of H-Ni-P complex, followed by alkene insertion into the Ni-H bond and reductive elimination (Scheme 8.45). 

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