Studies Of Nickel And Cobalt Catalyzed C-H Bond Functionalization Via Bidentate-Chelation Assistance

The transition metal-catalyzed functionalization of C-H bonds has been developed as an important organic synthesis method because of its advantages of simple steps and atomic economy.Over the past decades,significant advances have been made in the formation of new C-C or C-X bonds through the metal-catalyzed activation of C(sp2)-H bonds of arenes.However,the functionalization of unactivated C(sp3)-H bonds is still a particularly difficult challenge owing to its inertness.Meantime,although important results have been achieved through the C-H bond functionalization catalyzed by precious metals such as palladium,rhodium,ruthenium,and iridium.However,it is of great significance to develop more environmentally friendly and cheaper transition metal catalysts.This dissertation mainly focused on the studies of nickel and cobalt catalyzed C-H bond functionalization via bidentate-chelation assistance,especially on the nickel catalyzed sp3 C-H bond functionalization.The contents are as follows:1.Nickel-catalyzed direct thioetherification of β-C(sp3)-H bonds of aliphatic amidesThe sulfur-containing molecules are of considerable importance as versatile intermediates in organic synthesis and possess particular pharmaceutical relevancies.Catalytic methods for C-S bond formation represent a fundamentally important transformation and occupy a prominent position in modern synthetic organic chemistry.Herein,we reported a novel nickel-catalyzed β-thioetherification of unactivated C(sp3)-H bond of propionamides with the assistance of 8-aminoquinoline auxiliary,leading to the β-thio carboxylic acid derivatives.A broad range of functional groups is compatible with this thioetherfication reaction.The deuterium-labeling experiment illustrates that the C-H cleavage step occurs and is reversible.The process represents the first successful example of metal-catalyzed C-S bond formation from unactivated C(sp3)-H bonds.2.Direct ortho-thiolation of arenes and alkenes by nickel catalysisIn recent years,significant progress has been made in the use of arenes as substrates in the transition-metal-catalyzed C-H activation.In contrast,direct fuctionalization reactions rarely employ alkene substrates.After slight modification of the above reaction conditions,the nickel catalyzed thiolation of C(sp3)-H bond can be successfully extended to the thiolation C(sp2)-H bond.Herein,we have developed a highly efficient method for the direct thiolation of arenes and alkenes.By using the nickel catalytic system,not only the direct thiolation of aromatic C(sp2)-H bond could be smoothly approached to give the diarylsulfides in high yields(up to 98%),but also the vinylic C(sp2)-H bond participated in the transformation successfully to give the corresponding alkenyl sulfides in good yields,which provide an efficient alternative for the synthesis of alkenyl sulfides.3.An approach to five-membered lactams from aliphatic amides and terminal acety-lenes by nickel catalysisAmong various useful heterocyclic compounds,the lactam moiety is the privileged structural motif in terms of many complex natural products and pharmaceutical compounds with a broad range of biological activities.Over the past few years,many pioneering works for the efficient synthesis of lactam derivatives have been well explored,and the strategy for facile preparation of lactams though direct C(sp2)-H bond functionalization has been well applied in organic synthesis.In contrast,protocols involving the direct functionalization of sp3 C-H bonds are limited.In this paper,we investigated a new approach to the five-membered lactams through nickel-catalyzed alkynylation of C(sp3)-H bonds and consecutive annulation from aliphatic amides and terminal alkynes.A broad range of terminal acetylenes and aliphatic amides proved to be the efficient coupling partners,furnishing the corresponding lactams in moderate to good yields.The transformation is proven to undergo an oxidative alkynylation followed by the intramolecular annulation process.The methodology can be extended to aromatic amides and acrylamides,which provides the efficient and straightforward protocol for the construction of a variety of isoindolinone derivatives.4.Nickel-catalyzed stereoselective alkenylation of C(sp3)-H bonds with terminal al-kynesThe pivotal role of terminal alkynes as outstanding building blocks has attracted considerable attention of both industrial and academic laboratories for decades because of their prominent reactivity and vast number that are commercially available.A number of new transformations for applying terminal alkynes in the alkenylation of sp2 C-H bond as the reaction partners have been reported.However,the use of terminal alkynes in the alkenylation of unactivated sp3 C-H bond is still not achieved yet.In this paper,we discovered a nickel-catalyzed stereoselective alkenylation of unactivated β-C(sp3)-H bond in aliphatic amide with terminal alkynes using 8-aminoquinoline auxiliary for the first time.This reaction displays excellent functional group tolerance with respect to both aliphatic amides and terminal alkynes and features cheap nickel catalytic system.The 8-aminoquinolyl directing group could be smoothly removed and the resultant β-styrylcarboxylic acid derivatives could serve as versatile building blocks for further transformation.5.Direct ortho-acyloxylation of arenes and alkenes by cobalt catalysisWith target-oriented synthesis,C-O bonds could be traditionally forged through the condensation between carboxylic acids and alcohols or two molecule of alcohols.Over the past few decades,the acyloxylation of C(sp2)-H bond has attracted considerable interest owing to the huge value of the corresponding ester products in both academic research and industry.However,the involvement of precious metal was indispensable in these transformations.In this paper,we discolsed an efficient protocol of cobalt-catalyzed acyloxylation of arenes and alkenes with the assistance of 8-aminoquinolyl auxiliary.In this transformation,benzoic acids,alkenyl acids,and aliphatic acids could be readily involved to afford structurally diverse esters.It is worth noting that the Ag2SO4 oxidant is renewable and the directing group could be removed and recycled.The strategy represents the first successful example of transition-metal-catalyzed acyloxylation of alkenyl carboxamides C(sp2)-H bonds with carboxylic acids.