Hydrogen radical-shuttle (HRS)-enabled photoredox synthesis of indanones via decarboxylative annulation

• Published in: Nature communications Vol. 12; no. 1; p. 5257
• Main Authors: Yang, Bo, Li, Shi-Jun, Wang, Yongdong, Lan, Yu, Zhu, Shifa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.09.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/77/890; Carbonyl compounds; Carbonyls; Catalysis; Chemical reactions; Chemical synthesis; Density functional theory; Functional groups; Humanities and Social Sciences; Hydrogen; Hydrogen atoms; multidisciplinary; Organic chemistry; Outerwear; Photoredox catalysis; Protons; Radicals; Science; Science (multidisciplinary); Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25594-4

Hydrogen atom transfer (HAT) process is a powerful and effective strategy for activating C-H bonds followed by further functionalization. Intramolecular 1,n (n = 5 or 6)-HATs are common and frequently encountered in organic synthesis. However, intramolecular 1,n (n = 2 or 3)-HAT is very challenging due to slow kinetics. Compared to proton-shuttle process, which is well established for organic synthesis, hydrogen radical-shuttle (HRS) is unexplored. In this work, a HRS-enabled decarboxylative annulation of carbonyl compounds via photoredox catalysis for the synthesis of indanones is developed. This protocol features broad substrate scope, excellent functional group tolerance, internal hydrogen radical transfer, atom- and step-economy. Critical to the success of this process is the introduction of water, acting as both HRS and hydrogen source, which was demonstrated by mechanistic experiments and density functional theory (DFT) calculations. Importantly, this mechanistically distinctive HAT provides a complement to that of typical proton-shuttle-promoted, representing a breakthrough in hydrogen radical transfer, especially in the inherently challenging 1,2- or 1,3-HAT. Although hydrogen atom transfer is widely observed in synthetic organic chemistry, intramolecular hydrogen atom transfer between atoms separated by fewer than four bonds is kinetically slow. Here the authors show a method to form indanones, with hydrogen atoms shuttled across short distances by water.