Rapid synthesis of spirodienones via electrochemical dearomative spirocyclization in flow

Abstract

Preparation of the biologically relevant spirodienones from arenol derivatives is typically performed in batch using superstoichiometric oxidants. Herein, we have developed an electrochemical dearomative spirocyclization in flow, featuring the use...

Electrochemical Oxidative Dearomatization Strategy for Accessing Spiro[4.5]dienones and Derivatives

“…Although the potential of these substrates lies in a similar range as that of 1a, presumably, we anticipate the slower kinetics may be responsible for these poor outcomes. Based on the results from our experiments and relevant literature precedence, 5,36,37 To evaluate the synthetic potential, we conducted experiments for the applicability of the designed strategy and the molecule. Delightfully, a gram-scale reaction was accomplished to evaluate the scalability of this methodology (Scheme 5a).…”

Electrochemical Dearomative Amination of Phenol Derivatives: Access to Spirooxazolidinones

“…Based on the above results, a plausible mechanism was proposed in Scheme 5. First, anodic oxidation of 1 a gives radical cation A , followed by the intramolecular spirocyclization to afford radical B [10c,d] . Intermediate B is further oxidized at the anode to produce oxygenium cation intermediate C , which undergoes the nucleophilic addition of water and then eliminate a molecule of MeOH, [9f] or directly takes place the demethylation [9b,d] to obtain the product 2 a .…”

“…Very recently, Lei [10c] reported an electrochemical oxidative dearomatization of anisol derivatives to produce spiropyrrolidines. Ye [10d] developed an electrochemical dearomative spirocyclization in flow to afford spirolactams. Herein, we reported an electrochemical dearomative amination reaction to synthesize spirooxazolidinones (Scheme 1).…”

Electrochemical Dearomative Spirocyclization

“…Taking the advantages of continuous-flow electrolysis, including the requirement of low or no electrolyte dosage, short reaction time, and ease of scale-up reaction, Ye and coworkers have fulfilled the rapid, gram-scale preparation of structurally diverse spirodienones (Scheme 17). [46] They also established a base-dependent mechanistic proposal regarding the initial oxidation of the substrate. In the presence of acetate ion (path a), an electrochemical proton-coupled electron transfer process [47] via the single-electron oxidation of the complex of acetate and acylsulfonamide 75, was likely to deliver the amidyl radical [48] 76 for the follow-up radical spirocyclization (77).…”