Catalysts hydroamination/cyclization

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. 

Such lanthanide catalysts were also used in hydroamination/cyclization strategies for the synthesis of the alkaloid (+)-xenovenine. This reaction of enantiomerically pure 147 leading to 148 via two C-N bond formations was used in a late step of the synthesis after a hydrogenation, the natural product was isolated (Scheme 15.46) [100]. 

Ytterbium and lutetium ionic complexes, derived from enantiopure substituted (R)-binaphthylamine ligands of the general formula [Li(THF) ][Ln[(f )C2oHi2(NR)2]2], have been investigated as catalysts for hydroamination/cyclization of several unsatu- rated amines CH2=CH(CH2) C(R2)CH2NH2 (n = 1 or 2). Complexes with isopropyl or cyclohexyl substituents on nitrogen atoms were found to be efficient catalysts for the formation of N-containing heterocycles under mild conditions with enantiomeric excesses up to 78%.124... 

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]. 

Gribkov, D.V., Hultzsch, K.C., and Hampel, F. (2003) Synthesis and characterization of new biphenolate and binaphtholate rare-earth-metal amido complexes catalysts for asymmetric olefin hydroamination/cyclization. Chemistry - A European Journal, 9, 4796. 

A number of (R)- and (,S )-organolanthanide alkyl and amide complexes 1, bearing a homochi-ral substituent R on one cyclopentadienyl ring, were prepared and their catalytic activity in the enantioselective hydroamination-cyclization of 4-pentenylamines 3 was examined 11 113 These complexes are converted to the catalytically active species 2 in the presence of a large excess of the amine. Furthermore, catalyst epimerization (S)-2 to (/ )-2 or vice versa occurs and is complete in the early stages of preparative-scale reactions however, equilibrium homochiralities are frequently high, in some cases >95%. 

Pioneering experimental findings by Marks and coworkers [97,103,114] followed by theoretical analysis [109] allowed elucidation of the mechanism of aminoalkene hydroamination/cyclization (Fig. 13). The reaction is considered to proceed through a rare-earth metal amido species, which is formed upon protonolysis of a rare-earth metal amido or alkyl bond. As discussed in the previous section, the first step of the catalytic cycle involves insertion of the alkene into the rare-earth metal amido bond with a seven-membered chair-like transition state (for n = 1). The roughly thermoneutral [103,109] insertion step is considered to be rate-determining, giving rise of a zero-order rate dependence on substrate concentration and first-order rate dependence on catalyst concentration. 

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. 

Another interesting aspect is the metal size effect. In general, increasing ionic radii correlate with enhanced catalytic activity in hydroamination/cyclization of aminoalkenes [27,103,114], However, a different tiend is observed for phosphinoalkenes. Here, the mid-sized yttrium shows the highest reactivity, followed by lutetium and samarium, while the largest rare-earth metal, lanthanum, is the least active catalyst system [179],... 

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. 

Scheme 11.6 Proposed mechanism for the hydroamination/cyclization of aminoalkenes using alkali, alkaline earth, and rare earth metal based catalysts.

Scheme 11.8 Improved enantioselectivities in the hydroamination/cyclization of aminohexenes using a chiral octahydrofluorenyl yttrocene catalyst [38].

Scheme 11.9 Bisoxazolinato rare earth metal catalysts in the hydroamination/cyclization of aminoalkenes [49],...

More recently, the asymmetric hydroamination/cyclization of amino substituted stilbenes was studied utilizing chiral bisoxazoline lithium catalysts [73]. Enantios electivities reaching as high as 91% ee were achieved (Scheme 11.13). The reactions were performed in toluene at 60 °C to give the exo cyclization product 43 under... 

Tire first chiral group 4 metal catalyst system for asymmetric hydroamination/ cyclization of aminoalkenes was based on the cationic aminophenolate complex (S) 45 [85[. Secondary aminoalkenes reacted readily to yield hydroamination products with enantioselectivities of up to 82% ee (Scheme 11.14). For catalyst solubility reasons, reactions were commonly performed at 100 °G in bromobenzene using... 

Scheme 11.15 Hydroamination/cyclization of primary aminoalkenes using a neutral bis (phosphinic amido) zirconium catalyst system [88].

Scheme 77). The product 239 was converted to (+)-pyrrolidine-197B 240. The tandem hydroamination/ cyclization of the allenylalkenylamine 241 occurred in the presence of the samarium catalyst 201 to give the bicyclic pyrrolizidine 242 in a high yield (Scheme 78). Hydrogenation of 242 led to (+)-xenovenine 243. 

Qrganolanthanides such as metallocene or halfmetallocene andnomnetallocene lanthanide amides, alkylides, and hydrides are highly efficient catalysts for the intramolecular hydroamination/cyclization of a wide range of substrates such as aminoalkenes (Scheme 2), aminoalkynes, aminoal-lenes, and aminodienes. ... 

The aminoaUene hydroamination/cyclization reactions are highly diastereoselective and can provide concise routes to synthesize some natural products (Scheme 3). Using chiral organolanthanide complexes as catalysts, enantioselec-tive hydroamination/cychzation reactions are achieved, which provide a convenient route for the synthesis of chiral amines from simple, readily available prochiral substrates in a single step. 

Scheme 2 Several efficient catalysts for hydroamination/cyclization of aminoaUsenes...

The iridium complex 29, bearing a pincer ligand, was an efScient catalyst for the hydroamination/cyclization of secondary amines as shown in Equation (8.18). Remarkably, both Rh and Ir catalysts were found to be air and water stable, and no appreciable loss of catalytic activity was observed when carrying out the reaction in water as solvent. For example, the desired reaction product was observed in more than 98% yield (as observed by m NMR) using catalyst... 

Bauer EB, Andavan GTS, Hollis TK, et al. Air- and water-stable catalysts for hydroamination/cyclization. Synthesis and application of CCC-NHC pincer complexes of Rh and Ir. Org Lett. 2008 10 1175-1178. 

It has been proposed that Au-catalyzed asymmetric hydroamination/cyclization of amino-allenes proceeds through a catalytic cycle demonstrated in Scheme 39.3. The chiral Au-complex activates the allenes generating the complex A, which is attacked by nitrogen to form species B. Species B upon protonolysis releases the product and regenerates the catalyst. 

To meet the demand, the compound has been successfully synthesized by hydroamination/ cyclization of amino-allene 13" ° (Scheme 39.7). Enantio-selective addition of n-dibutyl zinc to allenyl aldehyde 10 using a chiral Ti catalyst (generated by heating the mixture of 11 and Ti(Ot-Pr)4 in dry toluene at 40-45 °C for 30 minutes) provides the corresponding hydroxyl... 

Zi G, Zhang F, Xiang L, Chen Y, Fang W, Song H. Synthesis and characterization of group 4 metal amides with new C2-symmetric binaphthyldiamine-based ligands and their use as catalysts for asymmetric hydroamination/cyclization. Dalton Tram. 2010 39 4048 061. 

---