Diels–Alder reactions for the rational design of benzo[b]thiophenes: DFT-based guidelines for synthetic chemists

In this work we studied the capability of several diene/dienophile pairs to undergo Diels–Alder (DA) reactions leading to benzo[b]thiophenes. A variety of synthetically and commercially available nitrothiophenes were chosen as dienophiles. Methyl 5-nitro-3-thiophenecarboxylate was selected as a potential strong electrophilic candidate based on some DFT-based properties and the substitution pattern of the expected product. The mechanistic details concerning the participation of this dienophile in polar DA reactions were investigated through a theoretical point of view. The results were compared with the experimental outcomes. This methodology should allow synthetic chemists to analyze DA reactions in detail in a stage prior to the synthetic job.

► Electrophile/nucleophile pairs in polar DA reactions leading to benzo[b]thiophenes.
► Methyl 5-nitro-3-thiophenecarboxylate is a potential strong electrophilic candidate.
► The mechanistic details were investigated through a theoretical point of view.
► The results were compared with the experimental outcomes.
► DA reactions can be analyzed in detail in a stage prior to the synthetic job.