Asymmetric α-C(sp)-H Allylic Alkylation of Primary Alkylamines by Synergistic Ir/ketone Catalysis

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jan 31

PMID 38296941

Authors

Jianyu Li

Sheng Gong

Shaolun Gao

Jianfeng Chen

Wen-Wen Chen

Baoguo Zhao

Affiliations

Soon will be listed here.

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 ~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 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-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.

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