Hydroamination/cyclization

B. Hydroamination/cyclization reactions catalyzed by amidinate and guanidinate complexes... 

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. 

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 aUcenes, as exemplified by the reaction of n-PrNH2 with 1-pentene catalyzed by a neodymium complex (Eq. 4.17) [127]. 

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]. 

Scheme 6.4 The proposed mechanism for the intramolecular alkane hydroamination/cyclization reaction (Equation 6.10)...

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... 

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... 

Most extensively, as well as most impressively, studied is the organolantha-nide-catalyzed hydroamination/cyclization of N-unprotected aminoolefins by... 

Scheme 17. Organolanthanide-catalyzed hydroamination/cyclization of N-unprotected aminoolefins...

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. 

The chiral organolanthanides have been especially designed for asymmetric catalysis. Thus far several enantioselective olefin transformations (hydrogenation, hydroamination/cyclization, hydrosilylation) as well as the polymerization of methyl methacrylate mediated by these chiral organolanthanide metallocenes have been investigated. 

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... 

Scheme 7. Hydroamination/cyclization of unsaturated amines catalyzed by (C5Me5)2Sm (Cp = C5Me5)...

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

D. Chiral organolanthanoid complexes for olefin hydrogenation, hydroamination/cyclization, and hydrosilylation... 

Figure 50. Proposed mechanism for catalytic asymmetric hydroamination/cyclization.

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

The catalytic activity of the Cp LnR complexes in hydroamination/cyclization of aminoolefins has been documented in terms of lanthanide size and other factors [186]. 

The C2-symmetric bisoxazolinate 175 formed complexes with lanthanides for the catalysis of enantioselective intramolecular hydroamination /cyclization <03JA14768>. 

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]. 

Figure 837 The proposed catalytic cycle of hydroamination/cyclization of aminoalkene.

The carbon-carbon unsaturated substrates have now expanded from aminoalkenes to aminoalkynes, aminoallenes, and aminodienes, and the hydroamination/cyclization reactions of these substrates have produced functionalized nitrogen-containing heterocycles. It is worth noting that the aminoallene hydroamination/cyclization reactions are highly diastereoselective, and can provide concise routes to the synthesis of some natural products (Figure 8.38) [126]. 

Ge, S.Z., Meetsma, A., and Hessen, B. (2008) Neutral and cationic rare earth metal alkyl and benzyl compounds with the l,4,6-trimethyl-6-pyrrolidin-l-yl-l,4-diazepane Ugand and their performance in the catalytic hydroamination cyclization of aminoalkenes. Organometallics, 27, 5339. 

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%. 

Type 4 metallocene complexes catalyze the regioselective mtermolecular addition of primary amines to acetylenic, olefinic, and diene substrates at rates which are = 1/1000 those of the most rapid intramolecular analogues [165]. Variants such as the intramolecular hydroamination/cyclization of aminoallenes [166] and the intra- and intermolecular tandem C-N and C-C bond-forming processes of aminodialkenes, aminodialkynes, aminoallenynes, and aminoalkynes [167] were applied as new regio- and stereoselective approaches to naturally occurring alkaloids. For example, bicyclic pyrrolizidine intermediate E... 

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