Precatalysts hydroamination

Ackermann and Bergman developed a highly reactive titanium precatalyst for the intramolecular hydroamination of allenes 149 [101]. The products 150 and in one... 

Highly regioselective intramolecular hydroamination of a y-aminoallenes has been achieved using a titanium bis (sulfonamide) as a precatalyst (Scheme 16.102) [107]. 

The complete catalytic reaction course for the intramolecular hydroamination/ cyclization of hepta-4,5-dien-l-ylamine in the presence of a prototypical [(/ -MesCsb LuCH(SiMe3)2] precatalyst has been critically scrutinized by employing a reliable... 

The same type of precatalysts catalyze the regiospecific hydroamination/ cyclization of aliphatic and aromatic aminoalkynes RC=(CH2) NH2 [295]. The mechanistic scenario parallels that of the corresponding aminoolefin cyclization. However, the cyclization of the aminoalkynes is 10-100 times more rapid, and a rather contrary effect of the cyclopentadienyl substitution on N, was observed. 

More recently chiral organolanthanide precatalysts of the type [Me2SiCp"(R Cp)]LnCH(SiMe3)2 and [Me2SiCp"(R Cp)]LnN(SiMe3)2 (R = ( + )-neomenthyl, (— )-menthyl Ln = Y, La, Sm, Lu) have been used for efficient regio- and enantioselective olefin hydroamination/cyclization processes. For example, a > 95% diasteroselectivity at 15 °C was achieved with... 

Intramolecular hydroamination/cyclization, the addition of an N-H bond across an intramolecular carbon-carbon unsaturated bond, offers an efficient, atom economical route to nitrogen-containing heterocyclic molecules (Equation 8.37). Numerous organolanthanide complexes were found to be efficient catalysts for this transformation [124, 125]. The real active intermediates are organolanthanide amides, which are formed by the rapid protonolysis reactions of precatalysts with amine substrates. The proposed catalytic cycle of hydroamination/cyclization of aminoalkenes is presented in Figure 8.37 [124]. 

A variety of bisoxazolinato rare-earth metal complexes such as 30 have been studied with regard to their hydroamination/cyclization catalytic activity [149]. The precatalysts show similar enantioselectivity and only slightly reduced catalytic activity when prepared in situ from [La N(SiMe3)2 3] and the bisoxazoline ligand. In this ligand accelerated catalyst system the highest rates were observed for a 1 1 metal to ligand ratio. 

Interestingly, although phosphines are slightly stronger Brpnsted acids than amines [182], protonolysis of the precatalyst Ln-N or Ln-C bond with a phosphine proceeds much slower than in case of hydroamination, which is attributed to the softer nature of phosphorous versus nitrogen [179] and a weaker Ln-P bond compared to the Ln-N bond [181,183]. Thus, in contrast to hydroamination, hydrophosphination is a protonation-controlled process, as shown by calculations [181],... 

The catalytic activity of the chiral complexes [Ln(L)Z2] shown in Scheme 70 was investigated in NMR-scale intramolecular hydroamination/cyclization reactions [135]. The rate dependence on the ionic radii of the center metal was studied by using 5 mol% bisoxazoline L32 and [Ln N(SiMe3)2 3] as precatalysts and 2,2-dimethyl-4-penten-l-amine as substrate (Scheme 71). The reaction rate as well as the enantioselectivities increased with increasing radius of the center metal. Therefore, the lanthanum compound 184 was the most active catalyst among the investigated complexes. 

Figure 11.1 Chiral lanthanocene precatalysts for asymmetric hydroamination [35, 36].

Unfortunately, the complexes underwent facile epimerization under the condi tions of catalytic hydroamination via reversible protolytic cleavage of the metal cyclopentadienyl bond (Scheme 11.7) [36, 38 40]. Thus, the product enantioselec tivity was limited by the catalyst s epimeric ratio in solution and the absolute configuration of the hydroamination product was independent of the diastereomeric purity of the precatalyst. Complexes with a (+) neomenthyl substituent on the cyclopentadienyl ligand generally produced the R) ( ) pyrrolidines, whereas ( ) menthyl and ( ) phenylmenthyl substituted complexes yielded the (S) (+) pyrrolidines, which is in agreement with the proposed stereomodel and solution studies on the equilibrium epimer ratios in the presence of simple aliphatic amines. 

The chemistry of organometallic group 4 metal compounds is well developed, thanks to their importance in polyolefin synthesis. Hence, their application in catalytic asymmetric hydroamination reactions is highly desirable. Group 4 metal complexes are commonly less sensitive and easier to prepare than rare earth metal complexes. Most important of all, many potential precatalysts or catalyst precursors are com mercially available. 

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. 

Scheme 9 Regioselective hydroamination of terminal alkynes promoted by precatalyst 13...

Group 4 bis(amidate)bis(amido) complexes have also been identified as precatalysts for the more challenging hydroamination of alkenes. The majority of investigations in this field focus on the intramolecular cychzation of aminoalkenes with zirconium-based catalysts. [64e] Neutral group 4 bis(amidate) zirconium amido or imido complexes are efficient precatalysts for the intramolecular cychzation of primary amines to form pyrrolidine and piperidine products (Scheme 12). The monomeric imido complex can be generated by reaction of the bis(amido) complex with 2,6-dimethylaniline and trapped with triphenylphosphine oxide. [64e] The bis(amido) and imido complexes... 

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. 

Scheme 14 Proposed catalytic cycle for hydroamination using zirconium precatalyst 10 in which the key step is a proton-assisted C—N bond formation...

Bis(pyridonate) zirconium complex 14, bearing sterically demanding pyridonate ligands, can be synthesized via protonolysis (Scheme 15), and is an active precatalyst for the intramolecular hydroamination of aminoalkenes to generate pyrrolidine and... 

Doye s group [81] showed that a dinuclear titanium-sulfonamidate complex (Scheme 21), with a tetrahedral sulfur in the ligand backbone, can be used for intermo-lecular hydroaminoalkylation as well. This system gives mixtures of branched and linear products, although to date there has been no mechanistic rationale provided for the reduced regioselectivity of group 4 metal complexes in this transformation. There has been one report by Zi s group [44] that describes axially chiral bis(sulfonamidate) tantalum and niobium complexes for application as precatalysts for hydroamination and hydroaminoalkylation. Unfortunately, these complexes did not show any reactivity for either of these reactions. 

Hydroamination. On exchanging two of the Et2N groups of the title reagent to A-(2,6-diisopropylphenyl)benzamido residues, a precatalyst for anti-Markovnikov hydro-amination of 1-alkynes to form aldimines is readily obtained. 

---