In Situ Reduction and Functionalization of Polycyclic Quinones

Abstract

Attempts to functionalize polycyclic quinones using lithium diisopropylamide as a base led to the unexpected formation of acenes. This reaction proceeds by electron transfer from the base to the electron deficient quinone, whose radical anion can react with a variety of electrophiles. Siloxy derivatives synthesized by this method could be easily isolated but showed poor photostability. In situ reduced intermediate generation is a convenient approach to functionalization of oxidatively unstable hydroquinones.

1H-1,2,3-Triazol-5-ylidenes as Catalytic Organic Single-Electron Reductants

“…First a single-electron transfer (SET) leads to the radical cation B Ph , followed by a H atom transfer (HAT) likely from tetrahydrofuran (BDE = 92 kcal·mol –1 ) as stated by previous reports on carbene radical cations. − Note that even under harsher conditions (excess A Ph and higher temperature), the second reduction of 1a was still not observed. Similar results have been reported by Thorley et al for the stochiometric reduction of quinones by lithium diisopropylamide (LDA, Scheme , blue pathway). , Indeed, calculations showed that the first reduction of the quinone is exothermic by 23.76 kcal·mol –1 , while the second reduction is endothermic by 14.32 kcal·mol –1 . However, it was demonstrated that the addition of an electrophile transforms the anionic semiquinone radical 2a into neutral radical 3a which can be readily reduced by LDA into the doubly reduced hydroquinone (Δ H = −28.9 kcal·mol –1 ).…”

“…Indeed, monitoring the catalytic reaction leading to 4a , we first recognized the EPR and UV signatures of the radical anion 2a , specifically, with a wide absorption band centered at λ max = 550 nm for the latter (Scheme ). After the addition of Me 2 SO 4 at room temperature, we observed a new EPR signal that we assigned to 3a . Then, by refluxing the solution without adding additional catalysts, Me 2 SO 4 or Cs 2 CO 3 , we observed the formation of 4a in an 83% yield.…”

“…Similar results have been reported by Thorley et al for the stochiometric reduction of quinones by lithium diisopropylamide (LDA, Scheme 3, blue pathway). 17,18 Indeed, calculations showed that the first reduction of the quinone is exothermic by 23.76 kcal• mol −1 , while the second reduction is endothermic by 14.32 kcal•mol −1 . However, it was demonstrated that the addition of an electrophile transforms the anionic semiquinone radical 2a into neutral radical 3a which can be readily reduced by LDA into the doubly reduced hydroquinone (ΔH = −28.9 kcal• mol −1 ).…”

“…Due to difficulties associated with quantifying the amount of radical anion formed, we chose to optimize the bis(reduction)/bis-(alkylation) process leading to bis(methylated)hydroquinone 4a, as Thorley et al did. 17 Usually, the deprotonation of triazolium salts C is performed with t BuOK. 19 However, after screening different parameters, including the base, solvent, and temperature (see SI for details), we obtained the best result using the procedure hereafter: (i) Anthraquinone 1a was mixed with 2.5 equiv of cesium carbonate and 20 mol % of triazolium C in degassed DMF.…”

“…Having shown that A Ph was able to act as a stoichiometric one-electron donor, the next step was to demonstrate that it could also act as a catalytic reducing agent following our hypothesis illustrated in Scheme b. Due to difficulties associated with quantifying the amount of radical anion formed, we chose to optimize the bis­(reduction)/bis­(alkylation) process leading to bis­(methylated)­hydroquinone 4a , as Thorley et al did …”