Asymmetric Hydroboration And Isomerization Of Alkenyl Ethers/Alkenyl Alcohols

Alkenes are important synthetic building blocks in mode rn organic synthesis,which can be transformed into a series of high-value chemicals through various functionalizations of carbon-carbon double bonds.The asymmetric hydroboration of alkenes has become one of the hot topics in synthetic organic chemistry and attracted considerable attention in the past few decades.However,current methods are largely limited to carbon atom-substituted alkenes,and examples of asymmetric hydroboration of heteroatom-substituted alkenes are rarely reported,especially for hydroboration of the enol ethers.Given the wide applications of organoboron compounds in materials science,medicinal chemistry,and the synthesis of natural products and fine chemicals,it is of great significance to develop asymmetric hydroboration of O-substituted alkenes.In addition,the catalytic isomerization of alkenyl alcohols has provide a new approach to obtain high-value aldehyde/ketone compounds.Although the development of catalytic isomerization of allyl alcohols is well established,the development of isomerization s trategies for long-chain alkenyl alcohols has been very slow and still challenging.This thesis mainly focuses on the asymmetric hydroboration of silyl enol ethers and the remote isomerization of alkenyl alcohols.This dissertation is divided into five chapters:Chapter 1: we described recent research progress in transition metal catalyzed asymmetric hydroboration of alkenes and isomerization of allyl alcohol according to transition metal species and substrate types.Chapter 2: the asymmetric hydroboration of alkenes has proven to be among the most powerful methods for the synthesis of chiral boron compounds.However,the catalytic enantioselective hydroboration of O-substituted alkenes has remained unprecedented.In this chapter,the catalytic hydroboration of silyl enol ethers with high enantioselectivities was achieved by utilizing two new chiral phosphine ligands we designed and synthesized.Both alkyl-and aryl-substituted silyl enol ethers are competent substrates to deliver a series of β-hydroxy boronic esters and diols under mild reaction conditions.Both the Z-and E-silyl enol ethers afford the product with the same absolute configuration under standard conditions using the same chiral ligand.Control experiments and DFT calculations disclosed that the chiral ligand is responsible for the above phenomenon.The utility of this method is illustrated by the gram-scale reaction and the transformations of borylether products.Chapter 3: after realizing the asymmetric hydroboration of aldehy de-derived silyl enol ethers,we developed a cobalt-catalyzed asymmetric hydroboration of ketone-derived silyl enol ethers,providing a new approach to access valuable enantiopure β-hydroxy boronic esters,and further enriched the scope of alkene hydroboration.This protocol used earth-abundant cobalt metal as a catalyst,with mild reaction condition and excellent enantioselectivities(up to 99% ees).The synthetic utilities of this approach were demonstrated by the gram-scale reaction and the transformations of β-hydroxy boronic esters and the synthesis of salmeterol and albuterol.Mechanistic experiments ruled out the formation of higher order speci es in this reaction,and suggested the excellent regioselectivity in the irreversible migratory insertion of a Co-H species to the silyl enol ether.Chapter 4: we developed an efficient rhodium-catalyzed remote isomerization of aromatic and aliphatic alkenyl alcohols into ketones.This catalytic process,with a commercially available catalyst and ligand,features high efficiency,low catalyst loading,good functional group tolerance,a broad substrate scope,and no stoichiometric additive.Preliminary mechanistic studies provide support for the dissociative chain-walking mechanism.