Hydroamination scope

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... 

Although the hydroamination of Michael systems is beyond the scope of this review, it is interesting to note the high yield (98%, TOE = 2 h ) obtained using the above cationic rhodium complexes for the hydroamination of 2-vinylpyridine with morpholine. Indeed, without catalyst, the hydroamination yield is only 5% [167]. 

Organometallic complexes of the /-elements have been reported that will perform both intra-and intermolecular hydroamination reactions of alkenes and alkynes, although these lie outside of the scope of this review.149-155 Early transition metal catalysts are not very common, although a number of organometallic systems exist.156-158 In these and other cases, the intermediacy of a metal imido complex LnM=NR was proposed.159,160 Such a species has recently been isolated (53) and used as a direct catalyst precursor for N-H addition to alkynes and allenes (Scheme 35).161,162... 

Iridium-Catalyzed Olefin Hydroamination (OHA) 151 Table 6.2 Widening the synthetic scope of the CMM system. 

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. 

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 mechanism and scope of rare-earth metal-catalyzed intramolecular hydrophosphination has been studied in detail by Marks and coworkers [147,178-181]. The hydrophosphination of phosphinoalkenes is believed to proceed through a mechanism analogous to that of hydroamination. The rate-determining alkene insertion into the Ln-P bond is nearly thermoneutral, while the faster protolytic o-bond metathesis step is exothermic (Fig. 22) [179,181]. The experimental observation of a first-order rate dependence on catalyst concentration and zero-order rate dependence on substrate concentration are supportive of this mechanism. A notable feature is a significant product inhibition observed after the first half-life of the reaction. This is apparently caused by a competitive binding of a cyclic phosphine to the metal center that impedes coordination of the phosphinoalkene substrate and, therefore, diminishes catalytic performance [179]. 

The catalytic activity of the ytterbium complex 170 was investigated in the hydroamination/cyclization reactions of aminoalkenes. Various nonactivated aminoalkenes were used as substrates (Scheme 43). The reaction scope is limited to five-membered ring formation. The aminoalkenes bearing bulky geminal substituents in P-position to the amino group are more reactive and could be... 

Transition metal catalysts from across the periodic table have been investigated for this transformation. [56b, 57] Early transition metal catalysts [58] are of particular interest due to their high reactivities, with reduced air and moisture sensitivity compared with the rare earth metal systems, and lower cost and toxicity compared with the late transition metal catalysts. The A,0-ligands generating tight four-membered metallacycles described above have been studied as precatalysts for hydroamination methodologies that display promising substrate scope and reactivity. 

Interestingly, by switching from bis(amidate) to bis(ureate) bis(amido) complexes, a broader scope of reactivity can be realized in intramolecular alkene hydroamination. [28] Reactivity studies indicate that the tethered zirconium bis(ureate) precatalysts are more reactive for intramolecular alkene hydroamination than the titanium analogs. 

A novel one-pot domino process was developed to synthesize substituted 1,2-dihydroquinoline derivatives 102 with high regioselectivity using a silver catalyst <05OL2675>. Scheme 29 shows the proposed pathway, which starts with the hydroamination of alkyne 103 and aniline 104. This is followed by C-H addition with another alkyne 103 and C-H addition cyclization to give intermediate 105. The final step is another C-H addition with alkyne 103 yielding the desired product 102. The scope and mechanism of this one-pot process is still under investigation. 

Recently, the scope of gold-catalyzed intramolecular exo-selective hydroaminations was expanded to allenic hydrazines and hydroxylaminesJ The former substrates afforded pyrazolidines in the presence of DTBM-SEGPHOS-Au complex J, whereas [Au2 (R)-xylyl-BINAP (OPNB)2] gave the best results in the cyclization of hydroxylamine derivatives to isoxazolidines. Excellent chemical yields and enantioselectivities were obtained in most cases, and the method was also applied to the synthesis of chiral tetrahydrooxazines. 

The most obvious chemistries to try next are chemistries closely related to hydroformylation, for example, the hydroaminations, hydrosUations, hydrocyanations, etc., using the metals noted throughout this chapter. The extension of CBER mechanisms to regio-, chemo- and stereoselective hydroformylation systems as well as the aforementioned chemistries should produce an incredibly rich variety of new results and go a long way towards classifying the scope of non-linear CBER mechanisms. 

This section focuses on hydroamination catalyzed by transition metal complexes, but many studies on hydroamination catalyzed by acid, base, - main group metals such as mercury and copper, and heterogeneous catalysts have been reported. Because the elementary steps of the mechanisms of these reactions lie outside the scope of this text, this chapter does not present details of the hydroaminations conducted with these t5q>es of catalysts. This material has been presented in many reviews. - ... 

The scope of hydroamination now includes many types of compounds containing N-H bonds and many types of alkenes and alkynes. Because the scope of these reactions is rapidly changing and many reviews of these processes have been published elsewhere, this section of the chapter provides a broad overview of the scope of these reactions. It then... 

The scope of hydroamination can be subdivided into the types of compounds containing N-H bonds that add to olefin or alkyne, or it can be divided into types of reagents containing carbon-carbon ir-bonds, such as alkenes, vinylarenes, dienes, allenes, and alkynes. Because the limitations of the catalysts and the rates of the reactions largely depend on the type of carbon-carbon Ti-bond involved in the reaction, this section of this chapter is divided into the reactions of alkenes, vinylarenes, allenes, dienes, and alkynes. 

Lanthanide complexes also catalyze the hydroamination of 13-dienes. The lanthanide catalysts originally developed for the intramolecular hydroamination of aminoalkenes are particularly active for the intramolecular additions of alkyl amines to dienes. The scope of this process is broad an illustrative example showing the high diastereoselectiv-ity of the cyclization of a chiral amine is shown in Equation 16.82. These reactions occur by insertion of the diene into a lanthanide-amide intermediate to form an allyl-metal intermediate. 

Among the first hydroaminations of alkynes to be published were cyclizations catalyzed by palladium complexes to form indoles. Hydroaminations of alkynes catalyzed by low-valent, late transition metal complexes occur with a narrower scope than the reactions catalyzed by lanathanide complexes. More recently, examples of the hydroaminations of alkynes catalyzed by rhodium complexes have been reported. 

Utimoto has also shown that simple gold(III) salts catalyze the intramolecular hydroamination of alkynes with arylamines [4]. For example, treatment of 2-(3,3-dimethyl-l.butynyl)aniline with a catalytic amount of sodium tetrachloroaurate in refluxing TH F for 30 min led to isolation of 2-f-butylindole in 90% yield (Eq. (11.3)). Marinelli has modified and expanded the scope of Utimoto s procedure through employment of ethanol, ethanol/water [5], or ionic liquids 6] solvents. As an example of this modified protocol, treatment of 2-alkynylaniline 2 with a catalytic amount of NaAuCU dihydrate in ethanol at room temperature for 6h led to isolation of 2-(4-chlorophenyl)indole 3 in 92% yield (Eq. (11.4)). A similar hydroamination protocol employing AUCI3 as a catalyst has been recently reported by Majumdar [7]. 

Widenhoefer and Bender have recently reported the gold(I)-catalyzed intramolecular hydroamination of unadivated C=C bonds with alkyl ammonium salts [56]. As an example, treatment of the HBF4 salt of 2,2-diphenyl-4-pentenyl amine (80 HBF4) with a catalytic 1 1 mixture of the gold(I) o-biphenyl phosphine complex (81)AuCl (81 = 2-dicyclohexylphosphino-2, 6 -dimethoxy-l,l -biphenyl) and AgOTf in toluene at 80 ° C for 24 h followed by basification with NaO H led to isolation of pyrrolidine 82 in 94% yield (Eq. (11.46)). Although the transformation was oflimited scope, gold(I)-catalyzed intramolecular hydroamination was also effective for primary 5-hexenyl ammonium salts and secondary 4-pentenyl ammonium salts. 

Table 15.7 Group 4 hydroamination on an expanded scope of aminoalkene substrates.

Previously reported bis(amidate)- and tethered-amidate-supported zirconium complexes can be used for alkene hydroamination catalysis, and all substrate scope and mechanistic investigations of these systems are consistent with the [2+2] cycloaddition mechanistic profile [61, 62). However, more recent catalyst systems that can be used with secondary amines show broader substrate scope, similar to that attained by rare earth elements and suggest a mechanistic similarity to that observed for previously intensely investigated rare earth hydroamination catalyst systems [7j. Such complexes are proposed to achieve ring closure via o-bond insertion, and thus, consideration of such a mechanistic profile in this case demanded further investigation. 

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