Cobalt‐Catalyzed Cross‐Dehydrogenative C(sp²)−C(sp³) Coupling of Oxazole/Thiazole with Ether or Cycloalkane

Abstract

Direct C5-alkylation of oxazole/thiazole with ether or cycloalkane has been achieved through a cobalt-catalyzed cross-dehydrogenative coupling (CDC) process in moderate to good yields. This transformation represents the first C(sp )-C(sp ) cross-coupling at the C5-position of the oxazole/thiazole via double C-H bond cleavages. Various functional groups on oxazole/thiazole substrates, as well as water and air, are well-tolerated with this concise and practical protocol, constituting straightforward access to heterocycles with great medicinal significance. A preliminary mechanism involving a radical process has also been proposed.

The Chemistry of Peresters

“…However, in contrast to the Cu‐promoted reaction, the resulting radicals have sufficient lifetime to be trapped by arenes or heteroarene co‐reactants. Moreover, while preferential reaction is observed at C‐H bonds activated by neighboring unsaturation or heteroatoms, even unactivated cycloalkanes are substrates for this reaction, although yields are somewhat lower than in activated systems …”

Recent Developments in Transition Metal‐Catalyzed Cross‐Dehydrogenative Coupling Reactions of Ethers and Thioethers

“…Ma, Z. Li and co‐workers expanded the scope of the cobalt‐catalyzed CDC reactions of oxazoles to obtain these heterocycles, as well as the analogous thiazoles, functionalized at the C‐5 carbon . This was the first example of this type of reactivity, which is of interest because there are many synthetic compounds containing this structural unit which are biologically active .…”

Palladium-Catalyzed Q-Tube-Assisted Protocol for Synthesizing Diaza-dibenzo[a,e]azulene and Diaza-benzo[a]fluorene Derivatives via O2 Acid-Promoted Cross-Dehydrogenative Coupling

“…The CDC approach has been used to develop new techniques for creating a set of bonds as part of sequences for the development of advanced complex organic compounds. An essential example is the formation of C–C bonds, which can be achieved through intermolecular − or intramolecular − CDC reactions between two C–H bonds in two different moieties or two neighboring C–H bonds in the same moiety, respectively. Furthermore, cross-coupling reactions were also developed for the formation of C-heteroatom bonds such as C–S, C–N, − C–O, and C–P, , in addition to, S–P and S–N bond formation.…”