Modular Synthesis of Polar Spirocyclic Scaffolds Enabled by Radical Chemistry

Abstract

Herein, we report a highly modular strategy to access spirocyclic scaffolds from abundant starting materials, i.e., cyclic ketones and α-amino or oxamic acids. The sequence proceeds through a straightforward Knoevenagel condensation, followed by a domino Giese-type reaction/base-mediated cyclization process, to deliver a broad scope of polar spirocyclic scaffolds in good to excellent yields. The products can be readily diversified, thus increasing the versatility of our method to gain rapid access to libraries of potential druglike molecules.

Modular synthesis of congested β2,2-amino acids via the merger of photocatalysis and oxidative functionalisations

“…Attempts to scale up the reaction were frustrated by the competitive formation of spirocyclic compound D1 (Scheme 2A). 21 We hypothesised that due to poor solubility of oxygen in organic solvents, the formation of ester 14 was hampered, thus favouring the pathway leading to D1 . We reasoned that the selective formation of the targeted β 2 -amino ester should be achieved by increasing the O 2 content in solution.…”

Photoredox-Enabled Deconstructive [5 + 1] Annulation Approach to Isoquinolones from Indanones in Water

“…Subsequently, radical substitution on ArSSAr with the acyl radical II provides thioester 3, which is further converted to amide V with benzylamine in the presence of KOH. The anionic intermediate VI formed by deprotonation 16 of V initiates an intramolecular cyclization to generate 54, which reacts with ArSSAr to provide the final product 5. Lastly, selected isoquinolones were tested against three plant pathogenic fungi in vitro, including Botrytis cinerea, Colletotrichum gloeosporioides, and Phytophthora infestans (Table S1).…”

“…Subsequently, radical substitution on ArSSAr with the acyl radical II provides thioester 3 , which is further converted to amide V with benzylamine in the presence of KOH. The anionic intermediate VI formed by deprotonation of V initiates an intramolecular cyclization to generate 54 , which reacts with ArSSAr to provide the final product 5 .…”