As ynthetic protocol for the preparation of 5-(aryl)dibenzothiophenium salts starting from inexpensive dibenzothiophene S-oxide and simple arenes is reported. The scope of the method regarding the nature of the arene is evaluated, intermediates along the reaction sequence have been trapped, and side-reactions identified. In addition, the X-ray structures of acomplete set of these salts are reported and their reactivities studied. Specifically,c hemoselective Suzuki coupling is observed at the dibenzothiophenium in the presence of iodides.
5-(Alkynyl)dibenzothiophenium
triflates are introduced as new reagents
to prepare different protein conjugates through site-selective cysteine
alkynylation. The protocol developed allows a highly efficient label
of free cysteine-containing proteins with relevant biological roles,
such as ubiquitin, the C2A domain of Synaptotagmin-I, or HER2 targeting
nanobodies. An electrophilic bis-alkynylating reagent was also designed.
The second alkynylating handle thus introduced in the desired protein
enables access to protein–thiol, protein–peptide, and
protein–protein conjugates, and even diubiquitin dimers can
be prepared through this approach. The low excess of reagent needed,
mild reaction conditions used, short reaction times, and stability
of the S–C(alkyne) bonds at physiological conditions make this
approach an interesting addition to the toolbox of classical, site-selective
cysteine-conjugation methods.
The reactivity of 5‐(alkynyl)dibenzothiophenium salts 1 is explored in the presence of different nucleophiles, dienes, and under photochemical conditions. Reaction with lithium acetylides affords diynes in moderate yields; while depending on the substitution pattern, the reaction with sulfinates delivers either the alkyne transfer products, alkynyl sulfones, or β‐(sulfonium) vinyl sulfones through addition to the C−C triple bond. Similar behavior is observed when tosylamines are used as nucleophiles. Salts of general formula 1 also react with dienes to render the corresponding Diels‐Alder cycloadducts. The vinyl sulfonium salts obtained by these routes further react with nucleophiles through a Michael addition, dibenzothiophene elimination sequence. Alternatively, they also engage in photoinduced radical cyclizations to produce substituted phenanthrenes. Attempts to use this specific addition/radical cyclization sequence for the construction of the 6a,7‐dehydroaporphine skeleton present in several families of alkaloids are also described.
A synthetic protocol for the preparation of 5‐(aryl)dibenzothiophenium salts starting from inexpensive dibenzothiophene S‐oxide and simple arenes is reported. The scope of the method regarding the nature of the arene is evaluated, intermediates along the reaction sequence have been trapped, and side‐reactions identified. In addition, the X‐ray structures of a complete set of these salts are reported and their reactivities studied. Specifically, chemoselective Suzuki coupling is observed at the dibenzothiophenium in the presence of iodides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.