摘要：Guang-Sheng Lu, Zhong-Lei Ruan,‡ Yan Wang,‡Jin-Fang Lü,Jian-Liang Ye, and Pei-Qiang Huang*

转自：康龙化成

Catalytic Reductive Amination andTandem Amination–Alkylation of Esters Enabled by a Cationic Iridium Complex

Guang-Sheng Lu, Zhong-Lei Ruan,‡ Yan Wang,‡Jin-Fang Lü,Jian-Liang Ye, and Pei-Qiang Huang*

Department of Chemistry and FujianProvincial Key Laboratory of Chemical Biology, College of Chemistry andChemical Engineering,Xiamen University, Xiamen, Fujian 361005,P. R. China

—Angew. Chem. Int. Ed. 2024,e202422742

Recommended by Murong Xu_MC3

KEYWORDS: Ircatalysis, Reductive Amination, Tandem Amination–Alkylation, N-monomethylation (反应类型), Esters(原料), secondaryand tertiary amines (产物),C(sp3)-N (成键类型)

ABSTRACT: Reportedherein is a convenient and efficient method for one-pot, catalytic reductiveamination, as well as the first multicomponent tandem reductive amination -functionalization of bench stable and readily available common carboxylicesters. This method is based on the cationic [Ir(COD)2]BArF-catalyzed chemoselective hydrosilylation ofesters, followed by one-pot acid-mediated amination and nucleophilic addition.The reaction was conducted under mild conditions at a very low catalyst loading(0.1 mol% of Ir),which could be further reduced to 0.001 mol%, as demonstrated by a reaction at a 15g scale. The method is highly versatile, allowing the use of esters with orwithout α-protons for the N-mono-alkylation of primary and secondary amines toproduce diverse secondary and tertiary amines, as well as α-branched/functionalizedamines. The method is highly chemoselective andtolerates a variety of functional groups such as bromo, trifluoromethyl,ester, and cyano groups. The value of the method was demonstrated by the one-step catalyticsynthesis of two bio-relevant N-mono-methyl α-amino esters and theantiparkinsonian agent piribedil, aswell as bythe use of twoshorter chain triglycerides as alkylating feedstock.

A.Methods for the N-alkylation and reductive N-alkylation of amines.

B.Reaction design for a divergent catalytic reductive amination and tandemreductive amination - functionalization of esters.

Reactionoptimization for the catalytic reductive ethyl benzoate to benzaldehyde

Reactionoptimization for the catalytic reductive amination of esters

Scope and chemoselectivity/functional group tolerance of the reductive N-alkylation reactions of secondary(A) and primary amines (B) with esters

Scope and chemoselectivity/functional group tolerance of the tandem reductive amination

Proposed reaction mechanisms of thecatalytic reductive amination and tandem reductive amination -functionalization of esters

Prof.Pei-Qiang Huang et al havedeveloped the first general methodology for the one-pot, divergent, catalyticreductive amination and tandem reductive amination - functionalization ofesters to produce secondary and tertiary amines, as well as α-functionalized secondary andtertiary amines. Utilizing the cationic iridium complex as a highly efficientand robust hydrosilylation catalyst, this method features: (1) very low catalyst loading (0.1 mol% of Ir andup to 0.001 mol% ata 15 g scale); (2) mild reaction conditions (room temperature to 50 °C, underambient atmosphere); (3) moisture and air insensitivity, allowing the reactionto be easily conducted in common synthetic organic and medicinal chemistrylaboratories without the need for Schlenk, high-vacuum, glovebox techniques, orautoclave apparatus; (4) excellent versatility for a wide range of commonesters, including triglycerides, and diverse amines, enabling direct access toboth secondary and tertiary amines, as well as α-functionalized amines via anovel reductive three-component reaction; (5) good chemoselectivity forN-mono-alkylation of primary amines and good functional group tolerance forsensitive functional groups such as bromo, iodo, fluoro, trifluoromethyl,olefin, esters, and cyano groups. The synthetic utility of this method was demonstrated by the one-stepcatalytic synthesis of medically important N-mono-methyl α-amino esters and theantiparkinsonian drug piribedil.Further extension of this novel synthetic methodology and exploration of itssynthetic utility are currently underway and will be reported in due course.

来源：新浪财经