Visible‐Light‐Mediated S−H Bond Insertion Reactions of Diazoalkanes with Cysteine Residues in Batch and Flow

Abstract

We describe the application of SÀ H bond insertion reactions of aryl diazoacetates with cysteine residues that enabled metal-free, SÀ H functionalization under visible-light conditions. Moreover, this process could be intensified by a continuous-flow photomicroreactor on the acceleration of the reaction (6.5 min residence time). The batch and flow protocols described were applied to obtain a wide range of functionalized cysteine derivatives and cysteine-containing dipeptides, thus providing a straightforward and general platform for their functionalizations in mild conditions.

Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry

“…More recently, a different approach to modify thiols, cysteine derivatives, and cysteine-containing dipeptides in flow was reported . In this case, diazoalkanes were used under visible light irradiation to perform a S–H bond insertion.…”

“…More recently, a different approach to modify thiols, cysteine derivatives, and cysteine-containing dipeptides in flow was reported. 737 In this case, diazoalkanes were used under visible light irradiation to perform a S−H bond insertion. In the flow setup (PFA coil 0.5 mm ID, 0.98 mL) irradiated with 50 W blue LEDs, a 110-fold increase in productivity was observed compared to batch, as the reaction time was reduced from 12 h in batch to 6.5 min in continuousflow.…”

Visible Light-Promoted Transformation of Diazo Compounds via the Formation of Free Carbene as Key Intermediate

“…对于氨基酸或者多肽的选择性修饰是生物化学以 及药物化学中需要解决的关键科学问题. 2020 年, 南京 工业大学邱江凯、郭凯等报道了可见光促进的芳基重氮 酯 1 对半胱氨酸骨架 48 中的 S-H 键的选择性插入反应 (Scheme 13) [29] . 机理验证实验表明, 反应可能是通过 自由基的途径进行的.…”

Solvent‐free, B(C6F5)3‐Catalyzed S−H Insertion of Thiophenols and Thiols with α‐Diazoesters

“…However, metal‐free approaches are still under developing (Scheme 1c) [14] . Quite recently, urea‐, visible light‐ and Brønsted acid‐catalyzed versions have been reported by the groups of Mattson (2014), [14a] Qiu and Guo (2020), [14b] Yang and Huo (2020), [14c] and Huang (2021) [14d] (Scheme 1c). Driven by the significant importance of the synthesis of these sulphur‐containing motifs and the meaningful organoborane catalysis research, we initiated the research project of the borane‐catalyzed S−H insertion with α‐diazoesters, which cultivated a solvent‐free protocol of this transformation presented herein (Scheme 1d).…”