Alkenes, activated, intermolecular hydroamination

Rare-earth metal complexes have proven to be very efficient catalysts for intramolecular hydroamination reactions involving aminoalkenes, aminoalkynes, aminoallenes, and conjugated aminodienes [88, 97]. They are significantly less efficient in intermolecular hydroamination reactions and only a limited number of examples are known [98-102]. The difficulties in intermolecular hydroamination reactions originate primarily from inefficient competition between strongly binding amines and weakly binding alkenes for vacant coordination sites at the catalytically active metal center. 

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]. 

INTERMOLECULAR HYDROAMINATION OF ACTIVATED ALKENES CATALYZED BY CHARGE-NEUTRAL HETEROLEPTIC COMPLEXES OF LARGE ALKALINE EARTHS... 

The catalytic activity of 4 in intermolecular hydroamination of alkynes by anilines as well as in the intramolecular alkene and alkyne hydroamination has been reported [40]. The results show that in the presence of ]PhNMe2H+][B(CgF5) ], 4 could catalyze these reactions very efficiently (2.5 mol% catalyst, 20 - 80 °C). It was su ested that the Cp moiety was protonolyzed to give Cp H, which was identified by NMR. In most cases, excellent yields were achieved, indicating a possible high potential of Zn-Zn-bonded complexes for catalytic organic transformations. As the presumed mechanism is not discussed further, it is hitherto unclear whether a Zn species is prevalent in the catalytic cycle. 

Although efficient for the intramolecular hydroamination/cyclization (abbreviated IH below) of aminoalkenes (see below), organolanthanides exhibit a much lower catalytic activity for the intermolecular hydroamination of alkenes, as exemplified by the reaction of n-PrNH2 with 1-pentene catalyzed by a neodymium complex (Eq. 4.17) [127]. 

Although alkali metal amides cannot catalyze intermolecular hydroamination of higher unactivated alkenes, allylbenzene derivatives react smoothly via base-catalyzed isomerization into p-methyl styrene derivatives, which are active enough to form hydroamination products (22) [170]. 

Due to its marked atom economy, the intramolecular hydroamination of alkenes represents an attractive process for the catalytic synthesis of nitrogen-containing organic compounds. Moreover, the nitrogen heterocycles obtained by hydroamination/cyclisation processes are frequently found in numerous pharmacologically active products. The pioneering work in this area was reported by Marks et al. who have used lanthanocenes to perform hydroamination/cyclisation reactions in 1992. These reactions can be performed in an intermolecular fashion and transition metals are by far the more efficient catalysts for promotion of these transformations via activation of the... 

Addition of ammonia and amines to alkenes (hydroamination) is thermodynamically feasible, but kinetically hindered, hence it requires activation of either of the reactants1,2,51. The intramolecular reaction is generally more easily accomplished than the intermolecular reaction and allows the stereochemistry to be controlled to a certain degree. 

As already mentioned, there has been significant progress in the development of chiral catalysts for asymmetric hydroamination reactions over the last decade. However, significant challenges remain, such as asymmetric intermolecular hydro aminations of simple nonactivated alkenes and the development of a chiral catalyst, which is applicable to a wide variety of substrates with consistent high stereochemical induction and tolerance of a multitude of functional groups as well as air and moisture. Certainly, late transition metal based catalysts show promising leads that could fill this void, but to date, early transition metal based catalysts (in particular, rare earth metals) remain the most active and most versatile catalyst systems. 

Stereochemical and kinetic analyses of the Brpnsted acid-catalysed intramolecular hydroamination/deuterioamination of the electronically non-activated cyclic alkene (13) with a neighbouring sulfonamide nucleophile have been found to proceed as an anh-addition (>90%) across the C=C bond to produce (15). No loss of the label was observed by and NMR (nuclear magnetic resonance) spectroscopies and mass spectrometry (MS). The reaction follows the second-order kinetic law rate = 2 [TfOH] [13] with the activation parameters being = 9.1 0.5 kcal moP and = -35 5 cal moP An inverse a-secondary kinetic isotope effect of d/ h = (1-15 0.03), observed for (13) deuteration at C(2), indicates a partial CN bond formation in the transition state (14). The results are consistent with a mechanism involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C(3) position coupled with an intramolecular anti-addition by the sulfonamide group. ... 

Some of the most active catalysts for the hydroamination of alkynes are based on lanthanides and actinides. The turnover frequencies for the additions are higher than those for lanthanide-catalyzed additions to alkenes by one or two orders of magnitude. Thus, intermolecular addition occurs with acceptable rates. Examples of both intermolecular and intramolecular reactions have been reported (Equations 16.87 and 16.88). Tandem processes initiated by hydroamination have also been reported. As shown in Equation 16.89, intramolecular hydroamination of an alk5me, followed by cyclization with the remaining olefin, generates a pyrrolizidine skeleton. Hydroaminations of aminoalkynes have also been conducted with the metallocenes of the actinides uranium and thorium. - These hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of the alkyne into a metal-amido intermediate. 

Magnesium A chiral magnesium complex has been shown to catalyse the intramolecular hydroamination/cyclizafion of amino alkenes R CH=CH(CH2) C(R R )CH2NHR at -20 C with <93% ee. The high activity of this system also allows for the catalytic intermolecular addition of pyrrolidine and benzylamine to styrenes, giving rise to the anti-Markovnikov products ArCH2CH2NR R. ... 

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