Olefin hydroamination latest

22 May 2015 - Organic chemicstry

Latest from the Baran laboratory: Olefin hydroamination. (Gui et al. DOI) Key ingredients: an alkene and a nitro arene together with triphenylsilane (2 eq.), ferric acetylacetonate (30 mole%), zinc, HCl and ethanol. The product: the alkylated amine. Product optimisation and substrate scope are all accounted for but where is the reaction mechanism? Relax, it is hidden in the supplementary info (350 pages!).

Any mechanism involving iron is insanely complex but here is this blog's attempt at some understanding. Phenyl silane transfers a proton to ferric acetylacetonate to form a ferric hydride species Fe-H. This species reduces the nitro arene to the Ar-NO nitroso compound and at the same time it reacts with the alkene to the alkyl radical. Both intermediates then react to form the hydroxylamine Ar-N(OH)-R or the N,O adduct Ar-N(R)-OR. The hydroxylamine is then converted to the amine by a another iron species and the N,O adduct is reduced by zinc. Replacing iron by cobalt or manganese killed the reaction by the way so iron is really key.

Drawbacks: the alkene is added in large excess. Side-products are the amine as direct reduction product and the N,O adduct. Typical yields are in the range of 50-60% which sounds like not a lot but the article notes that isolating amines from a reaction product in general is a challenge. Nitroalkanes perform badly. Ketone, alcohol, boronic acid and amine functional groups are tolerated.

And how about that 350 page supplimentary information? It also includes a photographic guide with lots of experimental-setup close-ups. Those Baran people really dislike keeping the lab tidy!. Also included is a handy Q&A: how exactly do you monitor a reaction?

new CRD entry:
Gui et al 2015.PNG