Hydroaminoalkylation intramolecular

Scheme 16 Inter- and intramolecular hydroaminoalkylation reactions for the atom-economic synthesis of selectively substituted amines...

Scheme 19 intramolecular hydroaminoalkylation of unactivated olefins with secondary amines catalyzed by mono- and bis(amidate) tantalum ami do complexes... 

An interesting observation in these investigations is the fact that intermolecular hydroaminoalkylation catalysts are not viable for application in intramolecular reactions. Furthermore, there are no catalysts that are effective for the intramolecular hydroaminoalkylation of secondary aminoalkenes and all high yielding examples of intramolecular hydroaminoalkylation are restricted to primary aminoalkenes. Meanwhile, intermolecular hydroaminoalkylation with primary amines has not yet been reported. 

Early examples of intramolecular hydroaminoalkylation were reported as side-products accessed unexpectedly during hydroamination investigations using group 4... 

Scheme 25 Intramolecular hydroaminoalkylation catalyst with excellent chemoselectivity...

Another limitation of the cyclopentadienyl-derived catalysts is their illustrated propensity for forming unwanted side products (Scheme 15.7) that result from unexpected C-C bond formation in an intramolecular direct a-aUcylation reaction, otherwise known as the hydroaminoalkylation reaUion [50]. The formation of this side product is problematic when targeting the heterocyclic products however, such reactivity is highly intriguing for the efficient preparation of amine-substituted carbocycles [51]. 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular hydroamination of alkynes [2], allenes [3], and alkenes [4] as well as the inter-molecular hydroaminations of alkynes [5] and allenes [6]. Primary aryl- and alkylamines readily react, but secondary amines have posed a greater challenge for this type of transformation with neutral catalysts [7]. For the reactions of the latter, cationic Zr and Ti complexes have been employed in intramolecular cyclizations of aminoalkenes [8]. Very recent work suggests that substrates that are difficult to hydroaminate may favor hydroaminoalkylations instead (Scheme 13.2) [9]. 

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