Research In The Synthesis Of α-Halo-α, β-Unsaturated Esters And O-H Insertion Of α-Diazo Carbonyl Compounds

α-Halo-α, β-unsaturated esters and α-diazo carbonyl compounds are two sorts of important compounds and have widely been applied in synthesis of medical and chemical products. New methods for the synthesis of α-halo-α, β-unsaturated and α-diazo carbonyl compounds have been investigated in this paper. In addition, the O-H insertion reaction of the α-diazo carbonyl compounds has been exploited. The main results are summarized as follows.1. The one-pot sequential oxidation-HWE reaction of alcohols in the presence of PCC and halo phosphonoacetates using DBU as base generated the corresponding α-halo-α,β-unsaturated esters, which were predominantly cis-isomers as expected. Various alcohols, such as arylic, vinylic and alkynic alcohols, were examined. α-Fluoro and α-chloro phosphonoacetates were used as substrates. It avoids the use of intermediate aldehydes because of volatility, toxicity, liability to oligomerisation, facile hydration, acerial oxidation, polymerization or isomerization. Therefore, the new method possesses obvious advantages, compared with HWE reaction using directly aldehyde as substrate. In addition, the configuration of the cis-vinylic alcohol was reminded in the corresponding product without any isomerization.2. α-Diazo-β-carbonyl-γ-alkynic ester derivatives were synthesized in two-step sequence starting from alkynic aldehydes. New O-H insertion products were generated via Rh₂(OAc)₄-mediated intermolecular O-H insertion reaction of the α-diazo-β-carbonyl-γ-alkynic esters with alcohols. Alkynic aldehydes, such as arylic and alkyl, were examined. Two kinds of alcohols, such as arylic and alkyl alcohols, were used as substrates.3. Three approaches to the synthesis of the α-diazo-β-carbonyl-γ-allyl esters were explored as follows.Firstly, the zinc-mediated Reformatsky reaction of a, /2-unsaturated aldehydes with methyl a-bromo acetates, initiated by iodine, was studied to give the corresponding /?-hydroxy unsaturated esters. Secondly, the treatment of ethyl diazo acetate with allyl aldehydes provided the or-diazo-y^-hydroxy-^-allyl esters in the presence of NaH, DBU or 6 mol % KOH + EtOH as base. Finally, the one-step condensation of cinnamyl chloride with ethyl diazo acetate afforded the ar-diazo-/?-carbonyl unsaturated esters in the presence of a base. However, the ideas should be further modified in future.The new compounds were determined by IR, 19F NMR, !H NMR, 13C NMR, or MS and so on.