Asymmetric α-C(sp3)-H allylic alkylation of primary alkylamines by synergistic Ir/ketone catalysis

Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their alpha-C-H bonds are unreactive towards electrophiles due to their extremely low acidity (pK(a)similar to 57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary alkyl amines by increasing the acidity of the alpha-amino C-H bonds by up to 10(44) times. This makes the alpha-amino C-H bonds acidic enough to be deprotonated under mild conditions. By combining DFO with an iridium catalyst, direct asymmetric alpha-C-H alkylation of NH2-unprotected primary alkyl amines with allylic carbonates has been achieved. This reaction produces a wide range of chiral homoallylic amines with high enantiopurities. The approach has successfully switched the reactivity between primary alkyl amines and allylic carbonates from intrinsic allylic amination to the alpha-C-H alkylation, enabling the construction of pharmaceutically significant chiral homoallylic amines from readily available primary alkyl amines in a single step.