Asymmetric α-C(sp<sup>3</sup>)-H allylic alkylation of primary alkylamines by synergistic Ir/ketone catalysis.
basic_science · Level V
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- Record sourced from PubMed, PMID 38296941.
- Also identified by DOI 10.1038/s41467-024-45131-3 and PMC identifier 10830461.
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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<sub>a</sub> ~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 10<sup>44</sup> 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 NH<sub>2</sub>-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.