| In this thesis,4-substituted tert-butyl3-oxo-2,8-diazaspiro[4.5]decane-8-car-boxylates were synthetized in three different methods using tert-butyl4-oxopiperid-ine-l-carboxylate as starting material. The advantages and disadvantages and application scope of each method were discussed. Sixteen target pruducts have been prepared and characterized by]H NMR、13C NMR、ESI-MS. All of the intermediates identified by’H NMR.Strategy one:The α,/β-unsaturated esters2a-c were abtained from tert-butyl4-oxopiperidine-l-carboxylate by using Wittig reaction. After undergoing Michael addition, reduction, and cyclization the desired diazaspiro compounds4a-b were obtained. The key step of this method was Michael addition reaction of the nitromethane, when R=H, the yield of4a was60%. When R=Me, the yield of the Michael addition did not increase obviously (only18%) although a variety of Lewis acids were used as catalyst. When R=Et, the corresponding Michael addition reaction product was not found. Therefore, this route could only be used to synthsize the spiro compounds which have no substituted groups (Scheme1).Strategy two:The α,β-unsaturated nitro compound12was generated from tert-butyl4-oxopiperidine-l-carboxylate1by using nucleophilic addition reaction and elimination reaction. Then a-substituted ester was introduced in by Michael addition reaction. After reduction of nitro and cyclization, the target products were obtained in moderate to good yields. This method could be applied to provide the derisved products which have the aromatic substituted group (Scheme2).Strategy three:Compound4a was firstly obtained by using strategy one, then protecting the amide nitrogen, modifying the a-site of carbonyl and removing the protecting group,4-substituted tert-butyl3-oxo-2,8-diazaspiro[4.5]decane-8-carbox-ylates19-20were produced. The key step of this route was the SN2reaction. This route was applicable to provide the4-alkyl diazaspiro compouds in moderate to good yields (Scheme3). |
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