Photoredox-Catalyzed Alkylation Of Carbonyl Compounds

The tertiary alcohol structure is widely present in natural products and drugs,but traditional methods of preparing tertiary alcohols by alkylation of carbonyl compounds require the use of stoichiometric reducing metals with poor selectivity.Although much progress has been made in follow-up research,many problems remain.Therefore,how to achieve this challenging goal efficiently and selectively under mild reaction conditions is of great research significance.Today,rapidly developing photocatalysis uses green,traceless photons as the driving force to efficiently achieve various chemical conversions by producing relatively controllable radical intermediates.In this context,we established a strategy of cross-coupling organic trifluoroborate and alkyl bromide and carbonyl compounds by visible photocatalysis based on the research concept of green,efficient and highly selective,respectively,to enrich and supplement the preparation methods of tertiary alcohol compounds.In the introduction part,this paper first briefly introduces photocatalysis,and then discusses some representative works involving carbonyl radicals in the reaction process,the main direction of which is visible photocatalysis.Finally,in Chapters 2 and 3,this article details the two parts of the research we have completed,which are as follows:1.Based on persistent radical effect,we developed a strategy for cross-coupling of carbonyl compounds and organic potassium trifluoroborate to obtain steric hindered alcohols.Using potassium benzyl trifluoroborate and methyl benzoylformate as model reactions,the optimal reaction conditions were determined by screening photocatalysts,solvents,additives,and reactant equivalents.Electron-deficient and electron-rich benzyl potassium trifluoroborate,aldehydes,ketones and ketone esters can be successfully applied to the system,and the highest yield can reach 90%.In the mechanism study,control experiments,ultraviolet absorption,fluorescence quenching,radical capture experiments and electron paramagnetic resonance experiments proved that the corresponding benzyl radicals and carbonyl radicals were generated during the reaction.The strategy was performed under mild reaction conditions,using the green organic dye4Cz-IPN as a photocatalyst and without the need for any additional oxidants or reducing agents.Potassium benzyltrifluoroborate plays a dual role in this reaction,first as a reactant,and secondly,the boron trifluoride released after its oxidation can also be used as a Lewis acid to activate carbonyl compounds,making the compound easier to be reduced.2.Based on halogen atom transfer,we further propose a strategy for cross-coupling of visible photocatalyzed carbonyl compounds and alkyl bromides.Using benzyl bromide and methyl benzoylformate as model reactions,we determined the optimal reaction conditions through screening of photocatalysts,solvents,additives,reactant equivalents,and silanes.Aldehydes,ketones,ketone esters,reactive alkyl bromide and inactive alkyl bromide can be adapted for this reaction.Possible reaction mechanisms were identified by control experiments,radical capture experiments,fluorescence quenching,cyclic voltammetry,and electron paramagnetic resonance experiments.The reaction combines halogen atom transfer with visible photocatalysis,allowing inexpensive and readily available alkyl bromides with high reduction potential to be directly applied to the system without any pre-activation.This avoids the pre-functional grouping process and has step economy.In addition,the reaction uses commercially available photocatalysts to obtain corresponding alcohol compounds with high selectivity under mild reaction conditions.