Photoredox Catalytic Installation of an Alkyl/Aryl Side Chain and Deuterium into (S)-Methyleneoxazolidinone: Synthesis of Enantioenriched α-Deuterated α-Amino Acid Derivatives

Abstract

A photoredox catalytic asymmetric method has been established for the installation of both aliphatic and aromatic side chains and the introduction of deuterium into the chiral methyleneoxazolidinone simultaneously. Efficient coupling of readily available boronic acids with the chiral auxiliary delivers structurally diverse α-deuterated α-amino acid derivatives with a high level of diastereoselectivity and deuteration.

Photocatalytic Radical Coupling of Organoborates with α-Halogenated Electron-Poor Olefins

“…As expected, the outcome of the reaction highly depends on the electronic nature of the aryl radical: the best results were obtained when the reaction involved arylboronic acids featuring radical-stabilizing electron-donating groups ( 3–16 ), with a consistent decline in isolated yield when using poorly activated arylboronic acids ( 17 and 18 ) and no reaction when the latter were engaged with methyl 2-bromoacrylate. Attempts at improving yields by adding CsF as a cocatalyst, as recently reported, unfortunately did not result in any amelioration. Representative heterocycles were also employed, albeit delivering the corresponding Giese adduct ( 19–22 ) in low yields.…”

Site-Selective Deuteration of α-Amino Esters with 2-Hydroxynicotinaldehyde as a Catalyst

“…Song et al developed the organocatalytic dynamic kinetic resolution (DKR) reaction of racemic azlactones with EtOD as a nucleophile as well as a deuterium source for the synthesis of α-deuterium-labeled amino acids . However, these methods often require prefunctionalization of substrates, − harsh conditions, , and poor tolerance of functional groups. − Takeda developed an approach for the preparation of α-deuterated amino acids by the DKR of racemates with the formation of Ni­(II) complexes derived from amino acids. The reaction can yield up to 96% α-deuteration but requires CD 3 OD as a deuterium source and an equimolar amount of NiCl 2.…”

“… 18 However, these methods often require prefunctionalization of substrates, 19 − 21 harsh conditions, 22 , 23 and poor tolerance of functional groups. 24 − 27 Takeda developed an approach for the preparation of α-deuterated amino acids by the DKR of racemates with the formation of Ni(II) complexes derived from amino acids. The reaction can yield up to 96% α-deuteration but requires CD 3 OD as a deuterium source and an equimolar amount of NiCl 2.…”

Cooperative Photoredox and N-Heterocyclic Carbene Catalysis Suzuki–Miyaura-Type Reaction: Radical Coupling of Aroyl Fluorides and Alkyl Boronic Acids

“…While the development of organic boronic acids in traditional organic synthesis is booming, it is still relatively lagging in the field of visible light catalysis, which may be due to the higher oxidation potential of organic boric acid. To overcome the above difficulties, some elegant strategies have been developed, including methods for reaction substrates, oxidizers, base, or solvent-assisted activation (Figure , A1). Despite the mentioned methods unfolding with some rationality and efficiency, the subsequent bonding methods for free radicals produced by organic boronic acids are rare.…”