Catalytic Intramolecular Hydroamination of Hindered Alkenes Using Organolanthanide Complexes

Abstract

The intramolecular hydroamination of hindered alkenes has been developed as a versatile route to heterocyclic systems. The current process utilizes the unhindered catalyst system [CpTMS 2LnMe]2 (Ln = Sm, Nd) to effect the cyclization of hindered amino olefins, providing products containing quaternary centers. The process tolerates a wide variety of substitution patterns, allowing the construction of monocyclic as well as fused and bridged bicyclic heterocycles. Two experimental procedures were employed in this study: one without solvent, minimizing waste streams, the other in deuterated solvents, allowing NMR monitoring of the reaction. The yield of each reaction was high, with NMR analysis of the reactions in progress showing clean conversion from starting material to a single product in most cases.

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“…Of the variety of metal‐based catalysts for this transformation, complexes of the lanthanides appear uniquely well suited for effecting chemoselective alkene hydroaminations under mild reaction conditions 2. 3 The vast majority of the complexes that have found utility for this purpose are comparatively air‐ and moisture‐sensitive metallocene derivatives. We recently disclosed that simple amido derivatives of the Group 3 metals corresponding to the formula [Ln{N(TMS) 2 } 3 ] ( 1 ; Ln=lanthanide, TMS=trimethylsilyl) are competent catalysts for intramolecular alkene hydroamination 4.…”

Asymmetric Hydroamination

“…Internal 1,1-or 1,2-disubstituted olefins 26 and 28 are much less reactive for hydroamination and require significantly harsher reaction conditions [39,[41][42][43][44]. The formation of pyrrolidines and piperidines often proceeds at comparable rates (Eq.…”

Transition Metal‐Catalyzed Asymmetric Hydroamination of Alkenes (AHA)

“…The hydroamination of 1,1-or 1,2-disubstituted olefins requires significantly harsher reaction conditions. [20] Internal alkenes 13 and 15 react only sluggishly at 80 -100 8C (Table 5).…”