Site-selective and versatile aromatic C−H functionalization by thianthrenation

• Published in: Nature (London) Vol. 567; no. 7747; pp. 223 - 228
• Main Authors: Berger, Florian, Plutschack, Matthew B., Riegger, Julian, Yu, Wanwan, Speicher, Samira, Ho, Matthew, Frank, Nils, Ritter, Tobias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2019; Nature Publishing Group
• Subjects: 140/131; 639/638/403/933; 639/638/549/933; 639/638/77; Acids; Alcohol; Aromatic compounds; Backup software; Carbon; Catalysis; Chemical bonds; Chemical plants; Chemical properties; Derivatives; Functional groups; Humanities and Social Sciences; Hydrogen; Letter; Meclofenamate; multidisciplinary; Photoredox catalysis; Salts; Science; Science (multidisciplinary); Selectivity; Structure-function relationships; Substitution reactions; Sulfur; Sulfur compounds; Transition metals
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-0982-0

Direct C–H functionalization can quickly increase useful structural and functional molecular complexity
1
–
3
. Site selectivity can sometimes be achieved through appropriate directing groups or substitution patterns
1
–
4
—in the absence of such functionality, most aromatic C–H functionalization reactions provide more than one product isomer for most substrates
1
,
4
,
5
. Development of a C–H functionalization reaction that proceeds with high positional selectivity and installs a functional group that can serve as a synthetic linchpin for further functionalization would provide access to a large variety of well-defined arene derivatives. Here we report a highly selective aromatic C–H functionalization reaction that does not require a particular directing group or substitution pattern to achieve selectivity, and provides functionalized arenes that can participate in various transformations. We introduce a persistent sulfur-based radical to functionalize complex arenes with high selectivity and obtain thianthrenium salts that are ready to engage in different transformations, via both transition-metal and photoredox catalysis. This transformation differs fundamentally from all previous aromatic C–H functionalization reactions in that it provides direct access to a large number of derivatives of complex small molecules, quickly generating functional diversity with selectivity that is not achievable by other methods.
A highly site-selective aromatic C–H functionalization reaction that does not require a particular directing group or arene substitution pattern provides functionalized arenes that can participate in various transformations.