銀(I)催化環己-2-烯-7-炔-1-醇進行分子內克來森類型重排反應合成芳香螺旋酮化合物
Abstract
螺旋化合物廣泛的出現在天然物與藥物的結構中，在有機合成領域中占有非常重要的地位，本文探討利用銀(I)催化，將帶有炔基的環己烯醇化合物進行分子內克來森類型重排反應，合成芳香螺旋酮化合物。
利用1,3-環己二酮進行碘置換反應得到3-碘環己烯酮，並與鄰碘苄溴製成的鋅銅試劑反應，得到帶有芳香環的環己烯酮碘化物。以硼氫化鈉將酮基還原之後，再經由Sonogashira反應將苯環上的碘與芳香乙炔行偶合反應，得到帶有芳香環的烯炔醇合環起始物。
將此帶有芳香環的烯炔醇化合物與0.2莫耳當量的銀(I)催化劑(AgSbF6)，在室溫下以1,2-二氯乙烷為溶劑，進行分子內克來森類型重排反應。反應在1分鐘內完成，得到一組非鏡像異構物的芳香螺旋酮化合物。將此組非鏡像異構物以Pd/C與H2將雙鍵氫化可得到單一的螺旋酮化合物。
Spiro compounds were often seen as a subunit in numerous biological interesting compounds. Therefore, they played an important role in organic synthesis. In this thesis, we reported that silver(I)-catalyzed intramolecular Claisen-type Rearrangement of cyclohexenol containing an aromatic alkynyl tether at C-3 produced aromatic spiroketones. 1,3-cyclohexandione was transformed to 3-iodocyclohexenone by reacting with iodine and triphenylphosphine. Addition of 2-iodobenzylzinc-copper reagent to 3-iodocyclohexenone generated 3-(2-iodobenzyl)cyclohex-2-enone. Sodium borohydride reduction of the resulting enone gave the allylic alcohol. The 3-(2-iodobenzyl)cyclohex-2-en-1-ol was treated with arylacetylene with PdCl2(PPh3)2 and triethylamine using Sonogashira reaction protocols to give the aromatic enynol starting materials. The aromatic enynol starting substrates were treated with 20 mol % of AgSbF6 in 1,2-dicloroethane at room temperature in 1 minute to produce aromatic spiroketones as a mixture of diastereomers in a ratio of 2 : 1. The formation of spiroketones were suggested via an intramolecular Claisen-type Rearrangement. The mixture of unsaturated spiroketones were further reduced of to saturated spiroketones by Pd/C and H2 to give a single spiroketones.
Spiro compounds were often seen as a subunit in numerous biological interesting compounds. Therefore, they played an important role in organic synthesis. In this thesis, we reported that silver(I)-catalyzed intramolecular Claisen-type Rearrangement of cyclohexenol containing an aromatic alkynyl tether at C-3 produced aromatic spiroketones. 1,3-cyclohexandione was transformed to 3-iodocyclohexenone by reacting with iodine and triphenylphosphine. Addition of 2-iodobenzylzinc-copper reagent to 3-iodocyclohexenone generated 3-(2-iodobenzyl)cyclohex-2-enone. Sodium borohydride reduction of the resulting enone gave the allylic alcohol. The 3-(2-iodobenzyl)cyclohex-2-en-1-ol was treated with arylacetylene with PdCl2(PPh3)2 and triethylamine using Sonogashira reaction protocols to give the aromatic enynol starting materials. The aromatic enynol starting substrates were treated with 20 mol % of AgSbF6 in 1,2-dicloroethane at room temperature in 1 minute to produce aromatic spiroketones as a mixture of diastereomers in a ratio of 2 : 1. The formation of spiroketones were suggested via an intramolecular Claisen-type Rearrangement. The mixture of unsaturated spiroketones were further reduced of to saturated spiroketones by Pd/C and H2 to give a single spiroketones.
Description
Keywords
銀, 分子內, 催化, 克來森, 芳香螺旋酮