Studies On Rhodium-Catalyzed Deoxygenative Functionalization Of Ketones

Ketones play an important role in organic synthesis because carbonyl groups can be effectively converted into other valuable functional groups,and have been widely used in agriculture,medicine and advanced materials.The conversion of carbonyl group to boronates via deoxygenative boration of ketones is one of the effective strategies for the conversion of carbonyl functional group.The most conventional method to construct the alkylboronates motif generally resorted to the hydroboration of alkenes.Compared to alkenes,ketones are abundant,inexpensive and readily available.In addition,ketones are also important raw materials for olefin synthesis.Therefore,the deoxygenative boration of ketones is an ideal strategy,and an important complement to the existing protocols for the synthesis of alkylboronates.The deoxygenative reduction of ketones has been considered an essential strategy,in which the conversion of carbonyl groups to methylene groups could be accessed.At present,the deoxygenative reduction of monocarbonyl ketones has been well developed,but the selective reduction of 1,3-diketones is rarely focused on.Therefore,it is of great significance to develop an effective strategy for selective deoxygenative reduction of 1,3-diketones.This thesis mainly focuses on the conversion of carbonyl functional groups using rhodium as catalyst,B2pin2 as a deoxygenative reagent,and the deoxygenative hydroboration of ketones and the selective deoxygenative reduction of 1,3-diketones were developed.The regiodivergent deoxygenative borylation of ketones could synthesize linear and branched alkylboronates as well as triboronates,in which the regioselectivity can be switched by the choice of ligand.In addition,we have achieved selective deoxygenative reduction of alkyl carbonyl groups in 1,3-diketones,providing a new method for selective reduction of 1,3-diketones.This dissertation is divided into four chapters as followed:Chapter 1 commenced with review on the deoxygenative boration of ketones and synthesis of alkylboronates in recent years,including the transition-metal-catalyzed or metal-free direct deoxygenative borylation of ketones and regiodivergent synthesis of linear and branched alkylboronates as well as the synthesis of 1,1,2-triboronates.Subsequently,the deoxygenative reduction of ketones was summarized,mainly from the aspect of deoxygenative reduction of monocarbonyl ketones and the current situation of selective reduction of 1,3-diketones.Chapter 2 developed the Rhodium-catalyzed regiodivergent synthesis of alkylboronates via deoxygenative hydroboration of ketones.This protocol represents the first example of regiodivergently preparing anti-Markovnikov and Markovnikov alkylboronates from readily available starting materials other than alkenes,and offering a new method to constitute alkylboronates.The great utility of this methodology has been demonstrated by the gram-sc ale reaction and further diversification of products.Mechanistic studies and DFT calculations revealed that the ketones first undergo the deoxygenation to give alkenes,which then go through ligand-controlled hydroboration to furnish linear and branched alkylboronates,respectively.The very different steric effects of PPh2Me and P(nBu)3 were found to be responsible for product selectivity.Chapter 3 developed the Rhodium-catalyzed deoxygenative boration of aryl ketones to synthesis 1,1,2-triboronates.This protocol exhibited good functional group tolerance,broad substrate scope and mild reaction conditions,and it would be an important complement and extension to the existing protocols for the synthesis of 1,1,2-triboronates.Mechanistic studies revealed that the alkene intermediate can alternatively undergo sequential dehydrogenative borylation and hydroboration to deliver the triboronates.Chapter 4 developed the Rhodium-catalyzed regioselective deoxygenative reduction of 1,3-diketones.This approach exhibited exceptionally high regioselectivity toward the aliphatic carbonyl reduction over aromatic carbonyl reduction,and high che mo selectivity toward the reduction of ketone over the olefin and ester.Moreover,this protocol exhibited good functional group tolerance,broad substrate scope,mild reaction conditions as well as application in the synthesis of biologically active molecules and later modification of natural products.Preliminary mechanistic studies revealed that this reduction went through the deoxygention of 1,3-diketones to α,β-unsaturated ketones and the subsequent 1,4-reduction to afford the desired reduction product.DFT calculations indicated that the lower energy barrier of the aliphatic C=O insertion into[Rh(I)]-Bpin versus the aromatic C=O insertion was responsible for the high selectivity.