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

ABSTRACT: Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C-H bonds are unreactive towards electrophiles due to their extremely low acidity (pK_a ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary alkyl amines by increasing the acidity of the α-amino C-H bonds by up to 10⁴⁴ times. This makes the α-amino C-H bonds acidic enough to be deprotonated under mild conditions. By combining DFO with an iridium catalyst, direct asymmetric α-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 α-C-H alkylation, enabling the construction of pharmaceutically significant chiral homoallylic amines from readily available primary alkyl amines in a single step.

SUBMITTER: Li J 

PROVIDER: S-EPMC10830461 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature