Cobalt-catalyzed Redox Transformaiton of Aldehydes and Ketones

Author:Jiang Zuo Zuo

Supervisor:liu dian sheng xu bao hua


Degree Year:2019





The transition-metal-catalyzed C–H functionalization of organic substrates shows an important application value in the fields of pharmaceutical chemistry,natural products and organic intermediate synthesis.Up to now,the majority of catalyzed these transformations were achieved by using noble metals.However,the highly chemoselective C–H functionalition catalyzed by the earth aboundant non-noble transition-metals bear more eco-friendliness and sustainability than precious transition-metals in the viewpoint of green chemistry.In this regard,the non-noble transition-metal cobalt has shows great potential in the alternative of traditional precious metals catalyzed C–H functionalization and organic systhesis as it’s particular redox activity.This thesis focused on the cobalt-based catalysis,the homogeneous systems of cobalt-catalyzed aerobic oxidative esterification and amidation of aldehydes,α,β–unsaturated ketone mediates the cobalt-catalyzed direct esterification of aldehydes and the in situ generated low-valent cobalt species catalyzed chemoselective transfer hydrogenation of(non)conjugated ketenes or aldehydes were developed,respectively.Meanwhile,the mechanism of each transformation was studied by the means of kinetics monitor,isotopic tracing,UV analysis,etc.the relative contents are concluded as fellows.1.A system of Co(II)/N,N’,N’’–trihydroxyisocyanuric acid(THICA)catalyzed aerobic oxidative esterification and amidation of aldehydes has been developed.Under this protocol,oxidative esterification of aldehydes was attained in the presence of p-CH3C6H4SO3H(Ts OH)as co-catalyst and using orthoformates as alkoxyl sources to furnish the dersired esters efficiently.In contrast,coupling of more nucleophilic amines with aldehydes render a readily occurred cross-coupling in the absence of any co-catalyst,but puts forward a new challenge owing to the potential inhibition of THICA upon nucleophilic substitution by amines.Consequently,only steric hindered amines were found tolerate in this catalytic system,while further condensation leading to imines were detected in the case of primary amines.Preliminary insight of the mechanism indicates such an oxidative C–O/N cross-coupling proceeded through an acetal/hemiaminal as the intermediate,subsequently,the intermediate was oxidated to the ester/amide efficiently in the help of O2/Co(II)/THICA catalytic system.2.Esterification of aldehydes with alkanols/aldehydes catalyzed by an in situ generated low-valent cobalt system was developed using α,β–unsaturated ketone as the oxidant or promoter,respectively.Various of aldehydes and alkanols were compatible with this protocol.Mechanistic studies revealed that the esterification of aldehyde and alkanol was proceeds via a Co(I)-catalyzed hydrogen-transfer route,wherein α–vinyl moiety in the bidentate α,β–unsaturated ketone functions as a hydride acceptor.In the catalytic cycle,the transformation progress involves neither the oxidation state change on the Co(I)centre nor a coordinatively unsaturated transient.On the other hand,the Co(I)-catalyzed aldehyde dimerization through a formyl C–H activation pathway.The kinetically disfavored hydride transfer therein was significantly increased by the C=C moiety of α,β–unsaturated ketone which reacted as a hydride transfer initiator.3.An in-situ generated low-valent cobalt with commercially bidentate phosphine system catalyzed chemoselective transfer hydrogenation of C=C and C=O bonds with equvalents i Pr OH as H-donor under base-free conditions was developed.For the conjugation enones,the vinyl group is selectively reduced and generate the corresponding saturate ketone ptoduct,whereas with nonconjugation alkenones,the selectivity is changed to the carbonyl group which afford an alkanol product.Preliminary mechanism studies disclose both transfer hydrogenations underwent a monohydride pathway.The reduction of enones undergo a concerted strategy which through an eight-membered ring involving a Co(I)center and obviates the carbonyl unit as the hydride acceptor.However,the transfer hydrogenation of nonconjugation alkenones,intramolecular hydride transfer from Co(I)–H which generated from the β–H elimination of a Co(I)–OR interminate to the carbonyl/formyl C=O moiety is preferring to undergo.