Synthesis Of Carbonyl Compounds From Organoboron Compounds

Organoboron compounds have various reaction pathways,and their diverse reactivity profile makes them one of the most important starting materials in synthetic chemistry.Among organoboron compounds,organoboronic esters exhibit extensive applications in pharmaceutical chemistry,material chemistry and chemical biology due to their ready availability,low toxicity and high stability.It is known that C-C（sp³,sp²,sp）bonds and various C-X（H,O,N,S,etc.）bonds can be constructed from C-B bonds.Among these transformations,the synthesis of carbonyl compounds from organoboronic est ers has become a research hotspot in the synthesis methodology in recent years.It provides an efficient,economical and green approach to the construction of carbonyl compounds.However,carbonyl compounds synthesized from organoboron compounds are largely limited to aryl ketones or aryl carboxylic acid derivatives.The construction of aliphatic ketones and complex carbonyl compounds such as lactones is still relatively limited.In addition,there are only a few examples of building chiral carbonyl compounds by this method.It is of great importance to develop new methods for constructing aliphatic ketones and complex,chiral carbonyl compounds from organoboronic esters because these carbonyl structures widely exist in drugs and natural molecules.This research work mainly focuses on constructing carbonyl compounds from organoboronic esters.In this research,lactones with two adjacent chiral centers have been constructed through the oxidation of enynyl boronates,and the asymmetric variant reaction of this oxidation has also been successfully achieved.In addition,in this study,allylic boronic esters can be smoothly converted to alkyl-alkyl ketones that are previously difficult to be synthesized from organoboron compounds.This research represented novel transformations of organoboron compounds and opened up new approaches for synthesizing drug and natural molecules.This thesis is divided into four chapters as follows:（1）The methods for constructing carbonyl compounds from organoboron compounds in recent years are summarized.The research progress is described according to the classification of alkyl,aromatic（alkenyl）and alkynyl boronic compounds.（2）A simple and mild oxidative lactonization of enynyl boronates has been developed.In this method,potassium monopersulfate triple salt（Oxone）and m-chloro-peroxybenzoic acid（m-CPBA）are used as oxidants and both of them are commercially available,cheap and stable.Manyβ-hydroxy-γ-lactones with various functional groups and spiro-,fused-cyclic skeletons have been constructed by this method.The control experiments revealed that the boron atom is critical to the success of the reaction.The oxidation pathways of the two oxidants were explored,and the reasons for the different diastereoselectivities（dr values）caused by different oxidants were explained.（3）An asymmetric oxidative lactonization of enynyl boronates has been established,and multiple chiralβ-hydroxy-γ-lactones and chiral spirocyclicγ-lactones have been constructed in this way.Products with high yield s and high enantioselectivities（ee value）were synthesized by controlling the p H of the system.In addition,gram-scale reaction has been successfully achieved,and the diverse transformations ofγ-lactones led to the formation of chiral unsaturated lactones,carboxylic acids,amide s and alcohols.Furthermore,natural product（R）-boivinianin A has been synthesized.The concise synthesis to the intermediate of natural product（-）-5-epi-eupomatilone-6 was successfully implemented,which effectively shortens its synthetic steps.（4）Rhodium-catalyzed one-step synthesis of ketones from allylic boronates and aldehydes has been developed.This reaction involves the subsequent processes of coupling and the isomerization.This method provides a new synthetic method for the synthesis of aliphatic ketones,and many alkyl-alkyl,aryl-alkyl ketones have been very efficiently constructed.This method exhibits a wide range of functional group compatibility,and it can be successfully conducted in gram-scale with reduced the amount of catalyst.The mechanistic study showed that the protodeboronation of homoallylic borylether intermediate in the presence of KHF ₂ and Me OH is the key to the success of the reaction.