Hydroamination zirconium catalyst

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

Zirconium Intermolecular hydroamination of both terminal and internal alkynes R C=CR with primary amines R NH2 to produce (after subsequent reduction) saturated secondary amines RiCH2-CH(NHR )R can be attained with the in situ generated zirconium catalysts (Me2N)4Zr (5 mol%) and sulfonamide (10 mol%). " Zirconium-catalysed intramolecular hydroamination (225) (226) has been studied theoretically " as for the analogous iridium-catalysed cyclization of (177) discussed (g) earlier " and similar conclusions have been reached regarding the hydrogen bonding, and so on. 

Diastereoselective cycUzations of chiral aminoalkenes were also achieved for zirconium catalysts (Table 6). Interestingly, the cyclization of primary aminoalkenes gave predominately tran -disubstituted pyrrolidines in accordance to observations for rare earth metal-based hydroamination catalysts [17, 67, 74, 80-82,99,121,122], while the c -diastereomer was favored in case of the secondary aminoalkene. Plausible transition states are shown in Fig. 9. The chair-like transition state leading to the traws-isomer of the primary aminoalkene is less encumbered due to reduced 1,3-diaxial interactions, whereas gauche interactions of the (V-substituent make the c -pyrrolidine the preferred product in case of secondary aminoalkenes. 

The development of group-4-metal-based catalysts for intramolecular hydro-amination of aUcenes has also led to several advanced systems for asymmetric hydroamination (Fig. 19). Most group 4 metal catalyst systems exhibit inferior reactivity and substrate scope (Table 19) in comparison to most rare earth metaland alkaline earth metal-based catalyst systems. They typically require high catalyst loadings and elevated reaction temperatures. However, the recent development of zwitterionic zirconium catalysts with significantly improved reactivities and selectivities [60, 118] promises to close this gap. 

Although zirconium bisamides Cp2Zr(NHAr)2 do not catalyze the hydroamination of alkenes (see above), they are catalyst precursors for the hydroamination of the more reactive double bond of allenes to give the anti-Markovnikov addition product (Eq. 4.96) [126]. 

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... 

Of more practical value zirconium bisamides can serve as catalysts for reaction of primary amines with alkynes to form cnamines. This reaction cannot be extended to alkenes, but allenes undergo this hydroamination to form imincs. 

Zirconium The new chiral zirconium complex (98) has been shown to catalyse intramolecular hydroamination of aminopentenes CH2=CHCH2CR2CH2NH2 [R2 = Mc2, Ph2, (012)4-, -(012)5-] to afford 2-methylpyrrolidines (89-98% ee). The rate law supports the mechanism involving a reversible substrate-catalyst interaction that precedes the RLS. A new mechanism for zirconium-catalysed hydroamination has been proposed, based on kinetic isotope effects and the significant effect of isotopic substitution on enantioselectivity. ... 

Previously reported bis(amidate)- and tethered-amidate-supported zirconium complexes can be used for alkene hydroamination catalysis, and all substrate scope and mechanistic investigations of these systems are consistent with the [2+2] cycloaddition mechanistic profile [61, 62). However, more recent catalyst systems that can be used with secondary amines show broader substrate scope, similar to that attained by rare earth elements and suggest a mechanistic similarity to that observed for previously intensely investigated rare earth hydroamination catalyst systems [7j. Such complexes are proposed to achieve ring closure via o-bond insertion, and thus, consideration of such a mechanistic profile in this case demanded further investigation. 

Several metal complexes with CCC pincer-type dicarbene ligands have been investigated over the years by the group of Hollis as catalysts for the intramolecular hydroamination/cychzation of unactivated alkenylamines. Initial studies concerned rhodium(III) and iridium(III) complexes of type 75, but later investigations were extended to complexes of the same ligands with group 4 metals such as zirconium, hafnium, and tita-... 

Watson DA, Chiu M, Bergman RG. Zirconium bis(amido) catalysts for asymmetric intramolecular alkene hydroamination. Organometallics 2006 25(20) 4731 733. 

More recently, neutral zirconium-based catalysts capable of performing reactions with both primary and secondary amines in intra- [55-57] and intermolecular [57, 58] reactions were reported. The imido mechanism is obviously impossible, and an insertion mechanism, similar to the lanthanide-like mechanism shown in Scheme 2 was proposed [55]. The isolation of an insertion intermediate in an intermolecular alkyne hydroamination reaction is compelling evidence in favor of the insertion mechanism [58]. 

A dramatic increase in reactivity was observed for the zwitterionic zirconium cyclopentadienyl-bis(oxazolidinyl)borate complex 33 [118]. The hydroamination reactions proceeded readily at room temperature, thus significantly exceeding the reactivity of most zirconium analogs. Despite the high reactivity, cyclization of the unsubstituted aminopentene did not proceed to high conversion even at high catalyst loading (Table 5, entry 10) possibly due to an autoinhibition [118]. 

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