Styrenes hydroamination

Hydroaminomethylahon of alkenes [path (c)j wiU not be considered [12]. This review deals exclusively with the hydroaminahon reaction [path (d)], i.e. the direct addition of the N-H bond of NH3 or amines across unsaturated carbon-carbon bonds. It is devoted to the state of the art for the catalytic hydroamination of alkenes and styrenes but also of alkynes, 1,3-dienes and allenes, with no mention of activated substrates (such as Michael acceptors) for which the hydroamination occurs without catalysts. Similarly, the reachon of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

Gaseous mixtures of styrene and NH3 have been claimed to give hydroaminated products over a ternary K/graphite/Al203 catalyst [45]. 

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. 

Lithium alkylamides (in situ generated from the amine and either n-BuLi or sec-BuLi) generally give higher yields under milder conditions. Thus, n-BuLi (5%) catalyzes the addition of primary and secondary amines to styrene to afford (-phenethy-lamines in moderate to good yields (e.g., Bq. 4.32) [155]. NH, and PhNHj, however, do not add to styrene under these conditions. a-Methylstyrene and 1,1-diphenyleth-ylene can also be hydroaminated. 

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). 

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

The only reported example of such hydroaminations concerns the IH of a-(aminoalkyl)styrenes (5-Exo-Trig process) (Eq. 4.36) [134]. 

Interestingly, significant progress has been made for the hydroamination of more reactive substrates such as styrenes, alkynes, dienes, and allenes. Specifically, highly selective catalysts have been discovered for the synthesis of fine chemicals (pharmaceuticals, natural products, chemical intermediates). In this area however, the problem of catalyst stabiUty can also be questioned in several cases. 

Some of the hydroarylation product is also observed substituted anilines afford the two products to varying degrees (Equation (15)). The closely related rhodium complexes [Rh(PCy3)2Cl]2, [Rh(dmpe)Cl]2 (where dmpe= l,2-bis(dimethylphosphino)ethane), and [Rh(C8H14)Cl]2 show essentially no catalytic activity.166 Application of [Rh(PEt3)2Cl]2 to the reaction of aniline with styrene gives a mixture of hydroamination and oxidative amination products, the latter predominating.167 Other related rhodium-catalyzed amination reactions (oxidative amination) have been reported.168 169... 

If the more activated alkene 2-vinylpyridine is used in place of styrene with the same catalysts and the same range of substrates, anti-Markovnikoff hydroamination is also found. Thus, N-[2-(2 -pyridyl)ethyl]piperidine was isolated in 53% yield from reaction of 2-vinylpyridine with piperidine in the presence of [Rh(COD)2]+/2PPh3 under reflux. N H addition was observed with other amines, the remaining product in all cases being primarily that from oxidative amination (Table 12). When the catalytic reaction was run in the absence of phosphine, the yield of hydroamination product increased dramatically.171... 

In order to account for the high regioselectivities observed in the rhodium-catalyzed hydroboration of styrenes, Hayashi proposed a modified mechanism which proceeds through 73-benzyl-rhodium complex 22 as a key intermediate (Scheme 7). Reductive elimination from this 73-benzyl-rhodium complex 22 produces the secondary alkylborane regioselectively.12 A related 73-benzyl-palladium complex was recently isolated by Hartwig in studies of hydroamination.75... 

In addition to C-alkylation reactions, hydroaminations are of great interest in organic synthesis [85, 86]. Recently, Shibasaki and coworkers developed a Bi(OTf)3-catalyzed intermolecular hydroamination using styrenes [87] and... 

Alkene hydroamination has been known for many years, but has been little used as a method in organic synthesis. Tobin Marks of Northwestern recently published a series of three papers that will make this transformation much mote readily accessible. In the first (J. Am. Chem. Soc. 125 12584,2003) he describes the use of a family of lanthanide-derived catalysts for intermolecular hydroamination of alkynes (to make imines, not illustrated) and alkenes. With aliphatic amines, the branched (Markownikov) product is observed, 1 — 2. With styrenes, the linear product is formed. When two alkenes are present, the reaction can proceed (3 —> 4) to form a ring, with impressive regioselectivity. 

Summaries of results of hydroamination mediated with Rh(I) amide complexes584 and comprehensive reviews giving detailed information of the field are available.585-587 Therefore, only the more important relatively new findings are presented here. In most of the transformations reported transition metals are applied as catalysts. The feasibility of the use of tcrt-BuOK was demonstrated in the base-catalyzed amination of styrenes with aniline.588... 

Keywords styrene, aniline, potassium tert-butoxide, hydroamination, microwave irradiation, /J-phcnylcthylamine... 

Iron salts (e.g. FeCls) have been identified as new catalysts for intramolecular hydroamination. A number of olefinic tosylamides underwent the reaction at 80 °C to form the corresponding the N-tosylpyrrolidine derivatives in good yield.63 The same salt can also catalyse Markovnikov addition of electron-rich arenes and heteroarenes to styrenes, giving rise to 1,1-diarylalkanes at 80 °C.64... 

The Brpnsted acidic anilinium salt [PhNH3+][ B(C6F5)4] has been developed as a catalyst for the hydroamination and hydroarylation of alkenes, such as styrenes, nor-bomene, cyclic alkenes, and cyclohexadiene, with anilines. The weakly coordinating... 

Electron-rich, electron-poor, and hindered styrenes (ArCH=CH2) undergo hydroamination with carboxamides (e.g. PhCONH2) in the presence of a 1 2 mixture of [PtCl2(H2C=CH2)]2 and (4-CF3CeH4)3P (5 mol%) in mesitylene at 140 °C for 24 h, to produce (PhCONH)CH(Me)Ar in moderate to good yields with excellent Markovnikov selectivity.90... 

A detailed mechanistic investigation revealed the steps of the anti-Markovnikov hydroamination of vinylarenes (81) with alkylamines catalysed by (COD)Ru(2-methyl-allyl)2, bis(diphenylphosphino)pentane, and TfOH. Treatment of the catalyst components with an excess of styrene under the catalytic conditions afforded a new... 

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)). 

Addition and cycloaddition. Styrenes are transformed into benzylatnine derivatives by hydroamination with TsNH2/" More unusual is the regioselective addition of arenes across the triple bond of an alkynylarene, as catalyzed by FeCls. ... 

Hydroamination. The addition of arylamines to styrenes to afford 7V-arylbenzylamines is promoted by Pd(OTf)2-BINAP, although catalytic systems constituting other Pd(II) salts with TfOH are also effective. Faster reactions are observed with styrenes that are relatively electron poor, and those bearing an ortho-substituent furnish products in high yields. 

Aromatic ketimines are formed by hydroamination of 1-alkynes with arylamines. Interestingly, styrenes afford adducts from o-aminoarylation. ... 

By building up the indole ring, A(-tert-prenylindole is also accessible. Willis and co-workers synthesised demethylasterriquinone A, isolated from the Congo fungus Pseudomassaria sp., from A-tert-prenyl indole which had been constmcted via Pd-catalysed condensation of 1,1-dimethylpropargylamine and a dihalogenated styrene derivative [62]. (9rt/jo-chlorinated alkynylbenzenes have been employed by Ackermann and co-workers in a Pd-catalysed N-arylation-hydroamination... 

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]. 

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