Iron-catalyzed Oxidation Of Tertiary Alcohols CC Bond Cleavage To Alkylation Of Quinones

Quinones are a class of important organic compounds,which are widely used in chemistry,materials,medicine and biology.Methyl-substituted quinones display unique biological activity.For example,vitamin K₁ and vitamin K₃ have good coagulation properties;Coenzyme Q₁₀ can drive ATP production,and plumbagin has good anti-cancer properties.Allyl-substituted quinones are also a very important class of bioactive compounds and important components of the cell membrane,which play important roles in cell metabolism and photosynthesis.Benzyl-substituted quinones are important intermediates for the synthesis of bioactive substances,and have been widely applied in medicinal chemistry.Therefore,new synthetic reactions that readily install methyl,allyl,and benzyl groups onto quinones are of great value to organic and pharmaceutical chemistry.This paper mainly includes three parts:(1)development of an iron-catalyzed oxidative methylation of quinones through unstrained tert-alcohol C-C bond cleavage;(2)development of an iron-catalyzed oxidative allylation of quinones through unstrained tert-alcohol C-C bond cleavage;(3)development of an iron-catalyzed oxidative benzylation of quinones through unstrained tert-alcohol C-C bond cleavage.Our primary research results are shown as follows:1.Iron-catalyzed oxidative methylation of quinones through unstrained tert-alcohol C-C bond cleavage has been developed.1,4-Naphthoquinone and 2-phenylpropan-2-ol were used as the model substrates to optimize the catalyst,oxidant,solvent,and temperature,respectively,and the methylation reagent was further optimized.The optimum conditions were obtained:Fe(NO₃)₃·9H₂O as the catalyst,K₂S₂O₈ as the oxidant,CH₃CN and H₂O as the solvent,2-phenylpropan-2-ol as methylation reagent and the reaction temperature of 80?.With the optimized conditions in hand,we examined the scope of the substrates.It was found that the method had good compatibility with various functional groups and gave the desired products in moderate to good yields.Notably,the protocol was successfully applied to the synthesis of drug molecules and modifed complex molecules.A preliminarily study of the reaction mechanism was conducted and indicated a free radical process in the transformation.2.Iron-catalyzed oxidative allylation of quinones through tert-alcohol C-C bond cleavage has been developed.1,4-Naphthoquinone and 2-phenylpent-4-en-2-ol were used as the model substrates to optimize the catalyst,oxidant,solvent,and temperature respectively,and then the allylation reagent was optimized.The optimum conditions were obtained:Fe(acac)₂ as the catalyst,(NH₄)₂S₂O₈ as the oxidant,CH₃CN and H₂O as the solvent,2-phenylpent-4-en-2-ol as the allylation reagent and the reaction temperature of80?.Under the optimal conditions,we explored the substrate scope.Various substrates worked well and high active groups can be tolerated.In addition,mechanism research indicated that the reaction proceeded in a free radical pathway.3.Iron-catalyzed oxidative benzylation of quinones through tert-alcohol C-C bond cleavage has been developed.1,4-Naphthoquinone and 2-methyl-1-phenyl-2-propanol were used as the model substrates to optimize the catalyst,oxidant,solvent,and temperature respectively.The optimum conditions were obtained:Fe Cl₃ as the catalyst,Na₂S₂O₈ as the oxidant,CH₃CN and H₂O as the solvent and the reaction temperature of80?.With the optimized conditions in hand,we first examined the scope of quinones for this transformation.Various substrates were well tolerated and the desired products were obtained over 80%yields.In addition,mechanism research found that the transformation was involved in a free radical process.