CO2と可視光でβ-アミノ酸を合成する新反応を開発〜計算科学のサポートに基づく環境調和型合成法を実現〜

2025-07-10

2025-07-10 北海道大学,静岡大学

北海道大学と静岡大学の研究グループは、CO₂とアミノアルケンを用いた新しいβ-アミノ酸合成法を開発しました。量子化学計算により、電子移動とCO₂の反応が同時に進行するメカニズムを解明。青色LEDと光電子移動触媒のみで高収率を達成し、環境調和型反応を実現しました。さらに、ウルトラファインバブルを活用した気液フロー法により、3分で高収率な連続合成が可能となり、持続可能な化学プロセスへの応用が期待されます。

<関連情報>

CO2を用いたアルケンのアミノカルボキシル化の計算化学的サポートによる開発:β-アミノ酸誘導体の合成 Computationally Guided Development of an Alkene Aminocarboxylation with CO2: Synthesis of a β-Amino Acid Derivative

Wataru Kanna,Yu Harabuchi,Kosaku Tanaka III,Hiroki Hayashi,Hideaki Takano,Tomoki Kozuka,Hiroto Sakurai,Nobuyuki Mase,Satoshi Maeda,and Tsuyoshi Mita
ACS Catalysis Published: July 4, 2025
DOI:https://doi.org/10.1021/acscatal.5c03580

Abstract

β-Amino acids are important structural motifs in synthetic organic chemistry owing to their applications as components in artificial peptides, which are intensively studied in pharmaceutical science. While various strategies exist for synthesizing α- and γ-amino acids from CO₂ via α-amino carbanion or α-aminoalkyl radical intermediates, direct and concise routes to β-amino acids remain rare. Herein, we report the computationally guided development of a photoredox-catalyzed aminocarboxylation of an aminoalkene with CO₂, affording a β-amino acid derivative under mild conditions. Although the demonstrated scope is currently limited, this transformation showcases a mechanistically distinct reactivity pattern enabled by photoredox catalysis. The reaction was inspired by our previous multistate reaction path network explored for Knowles’ hydroamination, where we found that a seam of crossing (SX) point for the potential energy surface involving a CH₃OH molecule facilitates product formation via proton-coupled electron transfer. Upon substituting CH₃OH with CO₂, the corresponding SX calculations indicated that the energetically concerted reduction–carboxylation mechanism is feasible. Indeed, cyclic β-amino acids were obtained from amino alkenes using [Ir(ppy)₂(dtbbpy)]PF₆ as a photoredox catalyst under irradiation with blue LEDs (440 nm). The developed photoreaction was successfully applied to a gas–liquid flow system under CO₂ pressure (1.0 MPa), in which the blue LEDs irradiated the tube line (total volume: 4.6 mL) for merely 3.2 min to afford the desired β-amino acids in good yield.