金(I)與三氟甲磺酸催化烯炔醯胺分子內環化反應：稠雙環- 與螺環-γ-內醯胺的合成

Abstract

本文包含兩個主題，一：金(I)催化六員環 3-烯炔醯胺化合物進行分子內環化反應合成雙環γ-內醯胺，二：三氟甲磺酸催化具對-甲苯磺醯基保護的3-(((芳香基乙炔)胺)甲基)環己-2-烯醇化合物進行分子內環化反應合成螺旋-γ-內醯胺。 以具芳香族取代的六員環 3-烯炔醯胺化合物為起始物，以金(I)催化進行分子內環化異構化反應得到9-氮三環[5.2.1.03,10]癸烷中間體，在空氣中可以直接氧化得到7-芳醯基全氫異吲哚酮衍生物；以鄰位芳香基取代與烷基取代的六員環 3-烯炔醯胺化合物為起始物時會得到4-氮三環[5.2.1.03,10]癸烷衍生物，此中間產物再加入四氧化鋨與N-甲基嗎啉-N-氧化物進行氧化可得到具7-芳(脂肪)醯基全氫異吲哚酮衍生物。

利用三氟甲磺酸催化具對-甲苯磺醯基保護的3-(((芳香基乙炔)胺)甲基)環己-2-烯醇化合物進行分子內環化異構化反應，首先得到六員環烯丙基碳陽離子中間體，水與此烯丙基碳陽離子以反式方式加成至炔基上，得到4-芳香基-2-含氮螺旋[4.5]癸-6-烯-3-酮衍生物，其為一組含氮螺旋非鏡像異構物，進一步將此混合物以鈀碳催化劑和氫氣還原後可得到單一4-芳香基-2-氮螺旋[4.5]癸烷-3-酮衍生物。The thesis contains two topics. The first part is the synthesis of bicyclic γ-lactams via gold(I)-catalyzed intramolecular cycloisomerization of six-membered ring 3-enynamides. The second part is the synthesis of spiro-γ-lactams via TfOH-catalyzed intramolecular cycloisomerization of N-tosyl protected 3-(((phenylethynyl)amino)methyl)cyclohex-2-enol. Six-membered ring aryl-substituted 3-enynamides, upon treatment with the gold catalyst, gave a 9-azatricyclo[5.2.1.03,10]decane intermediate, which was spontaneously oxidized to 7-aroyloctahydro-1H-isoindolone in air, while o-aryl-substituted and alkyl-substituted 9-azatricyclo[5.2.1.03,10]decane derivatives were isolated. These azatricycles could be further oxidized to 7-aroyl(alkanoyl)octahydro-1H-isoindolone by osmium tetroxide and N-methylmorpholine N-oxide. Treatment of N-tosyl protected 3-(((arylethynyl)amino)methyl)- cyclohex-2-enol with a catalytic amount of TfOH gave an allylic cationic intermediate Anti-addition of the allylic cation and H2O across the alkyne furnished 4-aryl-2-tosyl-2-azaspiro[4.5]dec-6-en-3-one derivatives after aqueous work up. The mixture of diastereomers was reduced by H2 and a catalytic amount of Pd/C to give 4-aryl-2-tosyl-2-azaspiro[4.5]decan-3-one as a single product.