Aminoalkenes, hydroamination cyclization

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. 

Fig. 13 Simplified catalytic cycle for aminoalkene hydroamination/cyclization [103,109]...

Hydroamination of Simple, Nonactivated Alkenes 349 Table 11.1 Lanthanocene catalyzed aminoalkene hydroamination/cyclization [35, 36]. 

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]. 

Aminoalkenes, oxidative cyclization, 10, 710-711 Aminoalkoxides, on zinc compounds, 2, 371 a-Aminoalkylallenes, cycloisomerizations, 10, 720 a-Aminoalkylcuprates, preparation, 9, 519-520 -Aminoalkylidynes, diiron carbonyl complexes with cyclopentadienyl ligands, 6, 248 Aminoalkynes, hydroamination, 10, 717 a-Aminoallenes, activation by gold, 9, 574 Amino r]5-amides, in Ru and Os half-sandwich rf3-arenes,... 

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]. 

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. 

Scheme 4 Catalytic hydroamination/cyclization of an aminoalkene with an internal double bond [104,125]...

The rare-earth metal-catalyzed hydroamination/cyclization of internal and terminal aminoalkynes is a facile process, as shown by experimental [105,106] and theoretical [110] studies. In general, the reaction proceeds via the same mechanism as aminoalkene hydroamination (Fig. 13) with some notable difference arising from a different insertive reactivity of the triple bond. The insertion of the C-C triple bond proceeds much faster than that of a double bond due to the exothermic nature of the step (Fig. 12). Overall, the cyclization of an aminoalkyne is commonly 1-2 orders of magnitude faster than that of an analogous terminal aminoalkene. However, the insertion step is still considered to be the rate-determining step, based on aforementioned DFT calculations and experimental observations. 

Interestingly, the reactivity pattern in rare-earth metal-catalyzed hydroamination/cyclization reactions of aminoalkynes with respect to ionic radius size and steric demand of the ancillary ligand follows the opposite trend to that observed for aminoalkenes, namely decreasing rates of cyclization with increasing ionic radius of the rare-earth metal and more open coordination sphere around the metal. This phenomenon can be explained by a negligible sterical sensitivity of a sterically less encumbered triple bond, as sterically less open complexes and smaller metal ions provide more efficient reagent approach distances and charge buildup patterns in the transition state [110]. 

The rare-earth metal-catalyzed cyclization of aminoalkenes, aminoalkynes and aminodienes generally produces exclusively the exocyclic hydroamination products. The only exception was found in the cyclization of homopropargylamines leading to the formation of the endocyclic enamine product via a 5-endo-dig hydroamination/cyclization (32) [142], most likely due to steric strain in a potential four-membered ring exocyclic hydroamination product. Interestingly, the 5-endo-dig cyclization is still preferred even in the presence of an alkene group that would lead to a 6-exo hydroamination product [142]. 

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 ytterbium complex 170 was investigated in the hydroamination/cyclization reactions of aminoalkenes. Various nonactivated aminoalkenes were used as substrates (Scheme 43). The reaction scope is limited to five-membered ring formation. The aminoalkenes bearing bulky geminal substituents in P-position to the amino group are more reactive and could be... 

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

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

Scheme 11.10 Catalytic hydroamination/cyclization of aminoalkenes using chiral amino thiophenolate yttrium complexes [61].

Scheme 11.11 Catalytic hydroamination/cyclization of aminoalkenes using 3,3 bisftrisarylsih substituted binaphtholate rare earth metal complexes [52].

Scheme 11.12 Lithium catalyzed asymmetric hydroamination/cyclization of aminoalkenes [72, 76],...

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 11.14 Hydroamination/cyclization of secondary aminoalkenes using a cationic chiral...

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

Equation 11.8. Organocatalytic asymmetric hydroamination/cyclization ofa sec ondary aminoalkene [111]. 

Scheme 11 Proposed mechanism for the organoactinide-catalyzed intramolecular hydroamination/cyclization of terminal and disubstituted aminoalkenes, aminoalkynes, aminoallenes, and aminodienes...

The insertion approach is very successful in the hydroamination of alkynes and alkenes catalyzed by lanthanide complexes developed by Marks et al. [220]. Thorough mechanistic studies have been undertaken for the intramolecular reaction (hydroamination-cyclization of aminoalkenes), although the intermolecular version of the process is also efficient [222]. The mechanism of the reaction can be represented in a simplified way by Scheme 6.68. The insertion step is almost thermoneutral, but the protonolysis of the M-aminoalkyl bond that follows is exothermic and provides the necessary driving force. The insertion of the alkene into the Ln-N bond is irreversible and rate determining and it goes through a... 

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