Theoretical Investigations On The Transition-metal-catalyzed Radical-mediated Organic Reactions

Transition-metal-catalyzed radical-mediated organic reactions have received attention in recent years.Comparing with traditional ionic reactions,this type of reactions has many advantages,such as relatively mild reaction conditions and shorter reaction time;broader functional group compatibility;easily oxidized or reduced adical intermediates and the wide range of applications of substrates;high atom utilization efficiency;having the advantage of activating or forming inert chemical bonds(such as C(sp3)-C(sp3))comparing with ionic reactions,etc.Therefore,transition metalcatalyzed radical-mediated organic reactions are expected to have broad research and application prospects.However,due to the high reactivity of radical inrtermediates and many undesirable side reactions,it is extremely challenging to achieve specific chemoselectivity,regioselectivity,especially stereoselectivity,which greatly restricts the progesses and applications of transition-metal-catalyzed radical-mediated organic reactions.Therefore,it is necessary to carry out systematic theoretical exploration in this field.The transition-metal-catalyzed radical-mediated organic reactions are initiated by single electron transfer(SET)between catalysts and organic substrates,we will conduct a systematic theoretical investigation on this type of reaction by means of quantum chemical methods.The main scientific concerns are as follows.First,we disclose how various types of organic substrates that may generate metal-bound radical intermediates but previously been proposed to generate free radical intermediates are activated by SET from metal catalysts to produce radical intermediates and the nature of bonding within the as-formed metal-bound radical intermediates,and elucidate the origin of the(chemo-,region-or/and even stereo-)selectivity of the reactions concerned.Second,for those reactions exhibiting seemingly dichotomous mechanistic behavior,we shall figure out which type of electron transfer is responsible for their redox process by exploring and comparing the energetics of their SET-and DET-type pathways,and,furthermore,elucidate the origin of their reaction mechanisms.Third,we will explor the substrates that are activated by SET from substrates to metal catalysts to produce metal-bound radical intermediates The reactions involving such substrates are rarely reported in transition-metal-catalyzed radical-mediated reactions.The theoretical and experimental exploration in this field is expected to offer a new way for the development of transition-metal-catalyzed radical-mediated organic reactions.Through in-depth research on the above problems,we shall try to design some new radicalmediated organic reactions that are catalyzed by inexpensive metals and,meanwhile,of high efficiency and industrial importance,and a systematic theory can be established for the transition-metal-catalyzed radical-mediated reactions.The details research of this thesis are as follows.1.From the perspective of substrates,we have discussed the mechanisms of Fe(Ⅱ)-catalyzed C-H cyanoalkylation of quinoxalin-2(1H)-ones using cyclobutanone oxime ester,Cu(Ⅰ)-catalyzed cyanoalkylation/cyclization of olefin with oxime ester,Cu(Ⅰ)-catalyzed dehydrogenative cyclization with oxime esters,Rh2-catalyzed transformation of hydroxy lamines and Mn(acac)3-catalyzed cyclization of vinyl azides and cyclopropanol,and we found that oxime esters,hydroxylamines and cyclopropanols can generate metal-bound radical intermediates,and the specific intermediates are Fe(Ⅲ)-iminyl radical(Stotal=2,SFe=5/2 and Siminyl=-1/2),Cu(Ⅱ)iminyl radical(Stotal=0,SCu=1/2 and Siminyl=-1/2),Rh2(Ⅱ,Ⅲ)-NH2 radical(Stotal=0,SRh2=1/2 and SNH2=-1/2),Mn(Ⅱ)-O-CH2radical(Stotal=2,SMn=5/2 and SCH2=-1/2)and the whole process follows a metal-bound radical mechanism for above reactions.These findings are expected to provide guidance for the experiment on the participation of these three types of compounds,so as to achieve efficient and controllable transitionmetal-catalyzed radical-mediated organic reactions.2.Due to the existence of metal-bound radicals,whether in some reactions the single electron transfer(SET)mechanism is incorrectly assumed as double electron transfer(DET)mechanism.In Chapter 3,we explored the mechanism of Cu(Ⅰ)catalyzed cyclization reaction of oxime ester with pyridine,and clarified the previously proposed DET mechanism is unreasonable,namely the Cu(Ⅰ)-Cu(Ⅲ)-Cu(Ⅰ)catalytic cycle.While further theoretical investigations show that the SET mechanism is feasible in the Cu(Ⅰ)-catalyzed cyclization of oxime esters with pyridines.The investigation on DET mechanism and SET mechanism not only illustrates that the metal-bound radical mechanism is general in the first-row transition-metal-catalyzed transformation of oxime esters,but clarifies that it’s easily to identify the original SET reaction as DET reaction in this type of reaction and misunderstand the overall reaction mechanism,and this issue deserves careful handling.3.The majority of transition metal-catalyzed radical reactions are initiated in the manner of SET from metal catalysts to organic substrates,namely the catalyst changes from a low oxidation state to a high oxidation state,including the reactions involving strained-ring substrates,azides and diazos mentioned above,as well as the Fe(Ⅱ)/Cu(Ⅰ)-catalyzed oxime ester reaction and the Rh2-catalyzed hydroxylamine reaction.In Chapter 5,we investigated the reaction involving cyclopropanol,which is the first substrate that initiated by SET from organic substrate to metal catalyst and forming the metal-bound radical.The work not only proves once again that the metalbound radical mechanism is universal in radical reactions,but also offer a new way for the development of transition-metal-catalyzed radical-mediated organic reactions.4.Rh2-catalyzed preparing aziridine reaction by using hydroxylamines have invoked intensive interest in recent years,but the nitrene intermediates[Rh2=NH]have been firmly deemed to be involved in these reactions,due to the misleading in early work.Our investigation indicates that this type of reaction is a metal-bound radical mechanism with[Rh2-NH2]radical as the key intermediate,rather than the previously proposed nitrene intermediates[Rh2=NH].Our work redresses the common mechanism of a series of works in this area,and is expected to provide theoretical guidance for the deep development of this reaction.