The Application Of Organozinc Reagents In Organic Synthesis

Organozinc reagent is one of the earliest prepared organometallics in organic synthesis.Organozinc reagents have already represented many advantages,such as excellent functionality compatibility,high chemoselectivity,regioselectivity and stereoselectivity etc,in organic synthetic chemistry because of their low reactivity. Additionally,they also can undergo transmetalation with a variety of transition metal salts or complex leading to new transition metal compounds,and the resulting organometallics can react with many organic electrophiles.The main work presented in this dissertation is focused on the application of organozinc reagents in the chain-extension reaction ofβ-diketones and C-C bond[1,2] migration.Additionally,Ring-opening reactions of 1,2-disubstituted cyclopropanols was also researched under different conditions.This dissertation includes five chapters.Chapter one:Preparation and application of organozinc reagents in organic synthesis.In the section,a brief introduction of the development of organozinc reagents in organic synthesis was given,and then reviewed in detail on the preparation and application of functional organozinc reagents in organic synthesis.Chapter two:Investigated the application of organozinc reagent in the ring-expansion and chain-extension reaction ofβ-diketones.In this chapter,we reported a simple and efficient ring-expansion and chain-extension reaction ofβ-diketones in the presence of organozinc reagent F₃CCO₂ZnCH₂I to form the corresponding productsγ-diketones in moderate to good yields.Under the excess amounts of mixture organozinc reagents,β-diketones would undergo chain-extension/cycloropanation reaction to afford trans-1,2-disubstituted cyclopropanols with good yields and high diastereoselectivity.At the same time,we have also investigated the influence of the electric effect and steric hindrance effect of the substituents to the yields and regioselectivity.Chapter three:Reported the application of organozinc reagent EtZnCH₂I in the aldol self-condensation and C-C bond[1,2]migration ofα-bromo ketones.In this chapter,we have developed a novel methodology for the synthesis ofβ-diketones from aromaticα-bromo ketones in the presence of Furukawa reagent under mild conditions.The present transformation is proposed to proceed via a Reformatsky-type reaction ofα-bromo ketones,followed by C-C bond[1,2]migration of the aldolate intermediate to giveβ-diketones in moderate to good yields.When extended the synthetic procedure to aliphaticα-bromomethyl ketones,the desiredβ-diketones were not obtained,at the same time,2,4-disubstituted furans or 1,2-disubstituted cyclopropanols were formed in moderate yields.And the relative stereochemistry of the substituents on the corresponding cyclopropanols was absolutely cis.And a plausible mechanism was proposed according to our experimental results.Chapter four:Described the application of Et₂Zn in the semipinacol rearrangement ofβ-bromohydrins.In this chapter,we studied the semipinacol rearrangement ofβ-bromohydrins promoted by Et₂Zn to obtain carbonyl compounds.A variety of ring-expansive and contractive carbonyl compounds were obtained in good to excellent yields according to the feature of the startingβ-bromohydrins.The advantage of this reaction includes as follows:mild reaction conditions,high efficiency and good yield,functionality tolerance and substoichiometric amount of organozinc reagent etc.Chapter five:Researched the ring-opening reactions of 1,2-disubstituted cyclopropanols in the presence of copper(â…¡)salt,acid and base.In this chapter,the ring-opening reactions of 1,2-disubstituted cyclopropanols, prepared fromβ-diketones,mediated by Cu(NO₃)₂,p-TsOH,and NaOH were investigated in detail.Ring-opening of 1,2-substituted cyclopropanols promoted by Cu(NO₃)₂ gaveα-methylene-β-diketones in good yields with high regieoselective cleavage of the cyclopropane at the bond "a".The reactions induced by p-TsOH in CH₂Cl₂ affordedα-methyl-β-diketones as the major products with minor amounts ofδ-diketones.The 2,3,5-trisubstituted furans were obtained in high yields when the ring-opening reactions were mediated by p-TsOH in methanol under reflux conditions. In the presence of sodium hydroxide the reaction proceeded smoothly in preference to the cleavage of the cyclopropane at the bond "b" to form major productδ-diketones.Through investigating the organozinc reagents mediated chain-extension rections ofβ-diketones,aldol self-condensation and C-C bond[1,2]migration ofα-bromo ketones and semipinacol rearrangement ofβ-bromohydrins,we have developed the new methodologies and extended the scope of the organozinc reagents in organic synthesis.More importantly,these new methodologies might be applied in some special fields,such as in the pharmaceutics and total synthesis of natural products et al and bring the unpredictable results.