Construction Of Sm/TMSBr Reduction System And Its Application In Pinacol Coupling Reaction

Divalent samarium（II）reagents such as Sm I₂,as single electron transfer reagent and a reducing agent,have been widely used in the field of organic synthesis.The study found that Sm Br₂ has showed more powerful reactivity than Sm I₂.However,the preparation of Sm Br₂ is not as convenient as Sm I₂,which limits its popularity in organic synthesis to certain extent.Our group is committed to the development of new bromine-containing divalent samarium（II）reagents.This article mainly studies the new Sm/TMSBr reaction system and its application in the aldehyde/ketone Pinacol coupling reaction.This dissertation consists of three parts:The first part is the literature review,which reviews the application of samarium（II）reagents in organic synthesis.It mainly includes the following contents:（1）Organic reactions promoted by divalent samarium reagents;（2）Organic reactions promoted by trivalent samarium reagents;（3）Organic reactions directly promoted by samarium metal.In the second part,the Pinacol coupling reaction of aldehydes and ketones promoted by the Sm/TMSBr system was studied.The influencing factors of the reaction were discussed,and the effects of other additives on Sm such as TMSCl,TMSI and BBr₃ et al were compared.Through experimental research,we found that in the presence of samarium powder（1 equiv.）,TMSBr（1 equiv.）,reaction time 0.5 hours,the aliphatic aldehydes and ketones in the Sm/TMSBr/THF system can proceed the Pinacol coupling reaction smoothly at room temperature and the expected 1,2-diols were synthesized in a good yields（46%-78%）.The reductive coupling of aromatic aldehyde/ketone compounds is relatively slower.The above experimental results are inconsistent with the literature reports where aromatic aldehydes and ketones undergo Pinacol reaction more readily than aliphatic aldehydes and ketones.Probe on the reaction mechanism was carried out by measuring the reduction potential of TMSX（X=Cl,Br,I）by cyclic voltammetry,determination of the by-products and comparison of the reductive potentials of aliphatic and aromatic ketones reported in literature.It is probable the reaction was first initiated by a key new organosilicon samarium species Me₃Si Sm（II）Br,which undergoes nucleophilic addition on the carbonyl of the aldehyde or ketone,followed by a Brook rearrangement to form a carbanion intermediate.The carbanion attacks another aldehyde or ketone finishes the coupling process and the cation exchange between Sm（II）and Me₃Si cation produces the disilylether of the Pinacol and Sm Br₂.Under the synergistic effect of metal samarium,Sm Br₂ reduces TMSBr into Me₃Si Sm（III）Br₂.Then the nucleohphilic silyl anion would undergo the similar reaction as Me₃Si Sm（II）Br to participate the coupling.In the third part,we studied the feasibility of the Pinacol coupling reaction of aldehydes and ketones catalyzed by Sm metal with TMSBr as the additive and magnesium as the terminal reducing agent.We found that in the presence of samarium powder（0.2 equiv.）,magnesium powder（1 equiv.）and TMSBr（1 equiv.）,reaction time 12 hours,the cycle of divalent samarium species can be realized efficiently,and the Pinacol reaction can still proceed.The reaction yields are moderate（33%-73%）,and the diastereoselectivity is close to the reaction promoted by equivalent samarium.This part of the research aims to reduce the amount of samarium powder and save rare earth metal resources,but the reaction results are still not very satisfactory.The unconsumed substrates and the alcohols produced by simple reduction are the main reasons for the low yield.In summary,the research in this dissertation is to develop a new type of samarium-based reductive-coupling system,achieved the Pinacol coupling reaction of aliphatic aldehydes and ketones under mild and simple conditions,broaden the application range of samarium reagent,and lay a good foundation for the further development of organosilicon samarium reagent.