Alkynes, activation hydroamination

The guanidinate-supported titanium imido complex [Me2NC(NPr02l2Ti = NAr (Ar = 2,6-Me2C6H3) (cf. Section IILB.2) was reported to be an effective catalyst for the hydroamination of alkynes. The catalytic activity of bulky amidinato bis(alkyl) complexes of scandium and yttrium (cf. Section III.B.l) in the intramolecular hydroamination/cyclization of 2,2-dimethyl-4-pentenylamine has been investigated and compared to the activity of the corresponding cationic mono(alkyl) derivatives. 

A catalytic system comprising TiCNMe ), LiNCSilVIej) and IMes has been developed for the intermolecular hydroamination of terminal aliphatic alkynes (1-hexyne, 1-octyne, etc.) with anilines [toluene, 100°C, 10 mol% TiCNMe ) ]. Markovnikov products were dominant. Substituted anilines reacted similarly. High conversions (85-95%) were observed with specific anilines. The optimum Ti/IMes/ LiN(SiMe3)2 ratio was 1 2 1. However, the nature of the active species and especially the role of LiN(SiMe3)2 are unclear [74]. 

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. 

K. Tani and Y. Kataoka, begin their discussion with an overview about the synthesis and isolation of such species. Many of them contain Ru, Os, Rh, Ir, Pd, or Pt and complexes with these metals appear also to be the most active catalysts. Their stoichiometric reactions, as well as the progress made in catalytic hydrations, hydroal-coxylations, and hydrocarboxylations of triple bond systems, i.e. nitriles and alkynes, is reviewed. However, as in catalytic hydroaminations the holy grail", the addition of O-H bonds across non-activated C=C double bonds under mild conditions has not been achieved yet. 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

The amide [Sm(45a) N(SiMe3)2 ] was a catalyst for an aUene-based hydroamination/ cyclisation. As an illustration, one such product upon hydrogenation yielded a naturally occurring alkaloid. Scheme 4.8. " " The same samarium(lll) amide was also active for the intramolecular hydrophosphination/cyclisation of phosphino-alkenes or -alkynes e.g., H2P(CH2)3C=CPh was transformed into 76. " ... 

The latter transformation requires the use of a small amount of an acid or its ammonium salt. By using [Cp2TiMe2] as the catalyst, primary anilines as well as steri-cally hindered tert-alkyl- and sec-alkylamines can be reacted.596 Hydroamination with sterically less hindered amines are very slow. This was explained by a mechanism in which equlibrium between the catalytically active [L1L2Ti=NR] imido complex and ist dimer for sterically hindered amines favors a fast reaction. Lantha-nade metallocenes catalyze the regiospecific addition of primary amines to alkenes, dienes, and alkynes.598 The rates, however, are several orders of magnitude lower than those of the corresponding intramolecular additions. 

Iridium(ni) hydrides, such as (98), proved to be air-stable active catalysts for intramolecular hydroalkoxylation and hydroamination of internal alkynes with proximate nucleophiles (e.g. 96). The cyclization follows the 6-endo-dig pathway with high preference (when regioselectivity is an issue).125... 

Although this mechanism is based on known activation of the N-H bond of aniline by Ru3(CO)i2, a mechanism involving the activation of the carbon-carbon triple bond followed by a nucleophilic attack of the amine carmot be discarded. Indeed, typical Lewis acids such as Zn(II) or Cu(I) salts have been shown to be efficient catalysts for the intramolecular hydroamination of alkyne [93], However, contrary to ruthenium(II) complexes, mthenium(O) catalysts are not expected to electrophili-cally activate alkynes. 

Whereas the catalytic hydrosilylation of alkynes was one of the first methods of controlled reduction and functionalization of alkynes, the ruthenium-catalyzed hydroamination of alkynes has emerged only recently, but represents a potential for the selective access to amines and nitrogen-containing heterocydes. It is also noteworthy that, in parallel, the ruthenium activation of inert C-H bonds allowing alkyne insertion and C-C bond formation also represents innovative aspects that warrant future development. Among catalytic additions to alkynes for the production of useful products, the next decade will clearly witness an increasing role for ruthenium-vinylidenes in activation processes, and also for the development of ruthenium-catalyzed hydroamination and C-H bond activation. 

Organolanthanide-catalyzed intermolecular hydrophosphination is a more facile process than intermolecular hydroamination. The reaction of alkynes, dienes, and activated alkenes with diphenylphosphine was achieved utilizing the ytterbium imine complex 9 (Fig. 8) as catalyst [185-188]. Unsymmetric internal alkynes react regioselectively, presumably due to an aryl-directing effect (48) [186]. 

Group 4 metal based catalysts have been studied intensively in hydroamination reactions involving alkynes and allenes [77 81], but (achiral) hydroamination reac tions involving aminoalkenes were only recently reported [82 84]. The reactivity of these catalysts is significantly lower than that of rare earth, alkali, and alkaline earth metal based catalysts. In most instances, gem dialkyl activation [37] of the aminoalk ene substrate is required for catalytic turnover. 

Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

Other examples of microwave-assisted catalysis include allylic alkylation, both palladium catalyzed and molybdenum catalyzed. In the latter case, air stable precursor complexes could be used under non-inert conditions. Microwave-enhanced Pauson-Khand reactions have also been reported, as have hydroamination of alkynes, and metathesis of functionalized alkynes. " Recently, microwave enhancement has been applied to C-H activation reactions, for example, for the formation of functionalized heterocycles, allowing the reaction to be performed with no solvent purification and minimal precautions to exclude air. A solvent-free chelation-assisted hydroacylation... 

The formation of alkyne oligomers that are concomitantly formed in the hydroamination reactions catalyzed by the thorium complexes indicates that two possible different complexes can be considered as active, conceivably with inter-conversion causing the occurrence of the two parallel processes. The discernment between these two most probable mechanistic pathways to find the key organometallic intermediate, responsible for the hydroamination process, was achieved by kinetic and thermodynamic studies (Scheme 5). The first pathway proposed the insertion of an alkyne into a metal-imido (M=N) bond, as observed for early transition metal complexes [101]. The second pathway suggested the insertion of an alkyne into a metal-amido bond, as found in some lanthanide compounds [39, 58, 84, 85]... 

The different modes of activation for the different organoactinides are indeed very unusual. For both organoactinide-imido complexes, a selective metathesis with the alkyne 7i-bond is operative (yielding the hydroamination products), whereas for the thorium complex a competing protonolysis reaction also takes... 

Scheme 8 presents a plausible mechanism for the intermolecular hydroamination of terminal alkynes promoted by the organothorium complex 1. The first step in the catalytic cycle involves the N-H a-bond activation of the primary amine by the organothorium complex yielding the bisamido-amine complex Cp2 Th(NHR )2 (H2NR ) (28) and two equivalents of methane (step 1). Complex 22 was found to be in rapid equilibrium with the corresponding bis(amido) complex 18 (step 2) [57, 60]. An additional starting point involved a similar C-H activation of the terminal alkyne with complex 1 yielding methane and the bis(acetylide) complex 17 (step 3). 

The synthesis of benzo[f ][l,4]diazepines 66 by a tandem hydroamination-cychzation sequence was carried out using a gold(I)-N-hetereocyclic car-bene catalyst (14JOM438). The authors utilized readily available N-alkyl o-phenylenediamines 63 and arylacetylenes 64 as starting materials. They proposed that the reaction proceeds by amination of a gold-activated alkyne with subsequent cyclization of intermediate 65. 

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