Catalytic intermolecular hydroaminations of unactivated olefins with secondary alkyl amines

Abstract

The intermolecular hydroamination of unactivated alkenes with simple dialkyl amines remains an unsolved problem in organic synthesis. We report a catalytic protocol for efficient additions of cyclic and acyclic secondary alkyl amines to a wide range of alkyl olefins with complete anti-Markovnikov regioselectivity. In this process, carbon-nitrogen bond formation proceeds through a key aminium radical cation intermediate that is generated via electron transfer between an excited-state iridium photocatalyst and an amine substrate. These reactions are redox-neutral and completely atom-economical, exhibit broad functional group tolerance, and occur readily at room temperature under visible light irradiation. Certain tertiary amine products generated through this method are formally endergonic relative to their constituent olefin and amine starting materials and thus are not accessible via direct coupling with conventional ground-state catalysts.

Figure 1

Reaction development A. Intermolecular anti-Markovnikov hydroaminations of simple alkenes with 2° alkyl amines are currently unknown. B. Thermodynamic challenges associated with hydroaminations of substituted alkenes. C. Kinetically facile C-N bond formation between aminium radical cations and unactivated alkenes. D. ARC-based protocol for intermolecular hydroamination of unactivated alkenes.

Figure 2

Proposed catalytic cycle for hydroamination.

Figure 3

Reaction scope. Reactions run on 0.5 mmol scale unless otherwise noted. Yields are for isolated material following purification unless otherwise noted and are the average of two experiments. All chiral products in this study are formed as racemates. Irradiation from two 34 W Kessel LED lamps. rt, room temperature. *Reaction run at 45 °C. ^†5.0 equivalents of olefin. ^‡3.0 equivalents of olefin. ^§1.5 equivalents of olefin. ^||Substrate is a trimethylsilyl enol ether. ^¶Isolated yield following acylative workup with Boc₂O to facilitate purification. ^#Reactions run on 0.2 mmol scale. **2-methylnon-1-ene as the olefin partner. ^††NMR yield.