Hydroamination anti-Markovnikov

It was thought that propionitrile came from dehydrogenation of the anti-Markovnikov hydroamination product, w-PrNHj. Propionitrile can break down to ethylene and HCN, the former reacting with NH3 to generate acetonitrile via ethyl-amine, the latter adding to propene to form the butyronitriles [26, 37]. 

Although N-(2-phenylethyl)morpholine is formed in only 14% yield (TOE = 0.3 h ), this is the first example of a transition metal-catalyzed anti-Markovnikov hydroamination of a non-activated olefin. Concerning the reaction mechanism, labeling experiments led the authors to favor activation of the N-H bond over olefin activation [166]. 

Hydroamination of olefins under most catalytic conditions proceed with Markovnikov addition of the N-H bond across the olefin. Shown below is a rhodium-catalyzed intramolecular, anti-Markovnikov, hydroamination developed for the synthesis of 3-arylpiperidines 167 <06JA6042>. Further evaluation of this reaction as a synthesis of multisubstituted piperidines revealed that substrates with substituents a or y to the amino group did not produce the expected piperidine, however, substrates with a substituent (1 to the amino group produce piperidines in high yield. 

Chatani and coworkers published an efficient method for the Rh(I)-catalyzed anti-Markovnikov hydroamination of terminal alkynes using either primary or secondary amines [58]. This reactivity had been observed earlier in the course of their studies on hydrative alkyne dimerization (Equation 9.8). 

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... 

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... 

Ruthenium complexes also catalyze the anti-Markovnikov hydroamination of vinylarenes. In this case, the combination of l,5-bis(diphenylphosphino)pentane (DPPPent), triflic acid, and a ruthenium(II) precursor generates a catalyst for the additions of secondary amines to vinylarenes (Equation 16.72). This mixture of catalyst components has been shown to generate a cationic Ti -arene complex of a PCP pincer ligand generated from the DPPPent ligand. The mechanism of this reaction involves nucleophilic attack of the amine on an Ti -vinylarene complex, as described in more detail in the section on the mechanisms of hydroamination. 

Finally, a much different catalyst, a lanthanocene, generates (3-phenethylamines from the anti-Markovnikov hydroamination of vinylarenes and primary alkylamines (Equation 16.73). These reactions occur with vinylarenes containing a range of electronic properties. The reaction is thought to occur by insertion of styrene into a lanthanum-amido complex. 

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

Alkyne hydroamination has been extensively reviewed [3, 4, 10] and important contributions using late transition metals have been realized to give the Markovnikov-type products most typically. Interestingly, in 2007, Fukumoto reported a tris(pyrazolyl borate)rhodium(l) complex for the anti-Markovnikov hydroamination of terminal aUcynes with both primary and secondary amine substrates, although yields with primary amines are always reduced compared to those with secondary amines (Scheme 15.26). Desirable functional group tolerance is also noteworthy for this regioselective hydroamination catalyst [187]. 

By changing to Rh as the catalyticaUy active metal in combination with the large-bite-angle chelating phosphine Hgand DPEphos, anti-Markovnikov hydroamination of vinylarenes with nucleophihc secondary amines can be realized (Table 15.20)... 

Related carbodiphosphoranes of Cu(I)- and Au(I)-t-butoxide complexes (47) have been prepared and rigorously characterized. Both complexes were explored for the anti-Markovnikov hydroamination of acrylonitrile with aniline (Scheme 15.59). The Cu(I) system provided higher conversions to product over the Au(I) complex, and under the reaction conditions explored, only the Cu catalyst yielded high conversions under an argon atmosphere [257]. 

Cationic Ni(II)-pincer complexes have also been exploited for the hydroamination of acrylonitrile with anihne [258]. Stoichiometric reactions in this case suggest that a Lewis acid mechanism promoting the anti-Markovnikov hydroamination is active (Figure 15.7) [258]. 

Scheme 15.59 The anti-Markovnikov hydroamination of acylonitrile with aniline using Cu-and Au-t-butoxide complexes.

Need a good system for the anti-Markovnikov hydroamination of an unactivated cdkene... 

SCHEME 3.128 Z-selective anti-Markovnikov hydroamination using ruthenium catalysts [140]. 

SCHEME 3.132 Base-assisted anti-Markovnikov hydroamination of phenylacetylene [142]. 

Need to carry out an anti-Markovnikov hydroamination reaction (E-selective) between an aniline and a terminal alkyne... 

A-Alkylation of amides and amines and dehydrative -alkylation of secondary alcohols and a-alkylation of methyl ketones " have been carried out by an activation of alcohols by aerobic oxidation to aldehydes, with copper(II) acetate as the only catalyst. A relay race process rather than the conventional borrowing hydrogen-type mechanisms has been proposed for the aerobic C-alkylation reactions, based on results of mechanistic studies. A Winterfeldt oxidation of substituted 1,2,3,4-tetrahydro-y-carboline derivatives provides a convenient and efiflcient method for the synthesis of the corresponding dihydropyrrolo[3,2-fc]quinolone derivatives in moderate to excellent yields. The generality and substrate scope of this aerobic oxidation have been explored and a possible reaction mechanism has been proposed. Direct oxidative synthesis of amides from acetylenes and secondary amines by using oxygen as an oxidant has been developed in which l,8-diazabicyclo[5.4.0]undec-7-ene was used as the key additive and copper(I) bromide as the catalyst. It has been postulated that initially formed copper(I) acetylide plays an important role in the oxidative process. Furthermore, it has been postulated that an ct-aminovinylcopper(I) complex, the anti-Markovnikov hydroamination product of copper acetylide, is involved in the reported reaction system. Copper(I) bromide... 

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

Munro-Leighton C, Delp SA, Alsop NM, Blue ED, Gunnoe TB (2008) Anti-Markovnikov hydroamination and hydrothiolation of electron-deficient vinylarenes catalyzed by well-defined monomeric copper(I) amido and thiolate complexes. Chem Commun 2008 111-113... 

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