路易斯酸輔佐六員環烯炔醯胺化合物的環化反應：橋及稠雙環δ-內醯胺化合物的合成

Abstract

本文包含兩個主題，一：金(I)催化4-炔醯胺甲基環己烯化合物的分子內環化反應，中間體含氮三環化合物經氧化形成橋雙環δ-內醯胺，二：三氟化硼乙醚輔佐第三丁基二甲基矽保護的2-(乙炔胺)甲基環己-2-烯醇化合物的分子內環化反應，合成六氫異喹啉酮衍生物。 以具芳香族取代的4-炔醯胺甲基環己烯化合物為起始物，在金(I)催化的條件下，進行分子內環化異構化反應，得到4-氮三環[4.2.2.03,8]癸烷中間體，將烷基與芳香族取代的三環併環中間產物，在四氧化鋨與N-甲基嗎啉-N-氧化物的條件下，進行氧化反應，可得到橋雙環δ-內醯胺，在酸性條件下，可以將烷基取代三環併環中間產物轉變成雙環[4.2.0]辛酮衍生物。 利用三氟化硼乙醚輔佐第三丁基二甲基矽保護的2-(乙炔胺)甲基環己-2-烯醇化合物的分子內環化反應，直接合成六氫異喹啉酮衍生物，通過差向異構化(epimerization)反應，將一組六氫異喹啉酮的非鏡像異構物，轉變成單一非鏡像異構物的六氫異喹啉酮衍生物。

The thesis contains two topics. The first part is the synthesis of bridged bicyclic δ-lactams via gold(I)-catalyzed intramolecular cycloisomerization/ox -idation of N-tosyl-4-ynamidomethylcyclohexenes. The second part is the synthesis of hexahydroisoquinolinone derivatives via BF3.OEt2-promoted intramolecular cyclization of alkyl- or aryl-substituted O-silyl-protected 2-((ethynylamino)methyl)cyclohex-2-enols. N-Tosyl-4-ynamidomethylcyclohexenes underwent cycloisomerization in the presence of a catalytic amount of a gold(I) complex delivering 4-azatricyclo[4.2.2.03,8]dec-2-ene derivatives as the major products under mild reaction conditions with high diastereoselectivities. Upon oxidation with osmium tetraoxide and N-methylmorpholine-N-oxide, alkyl- or aryl-substituted azatricycles led to bridged bicyclic δ-lactams. Under acidic conditions, the alkyl-substituted azatricycles were further transformed into 4-N-tosylaminomethyl-tethered bicyclo[4.2.0]octan-7-ones derivatives. The BF3.OEt2-promoted intramolecular cyclization of alkyl- or aryl-substituted O-silyl-protected 2-((ethynylamino)methyl)cyclohex-2-enol enables a straightforward approach to hexahydroisoquinolinone derivatives. Upon epimerization with 1,8-diazabicyclo[5.4.0]undec-7-ene, the mixture of diastereomers afforded hexahydroquinolinone derivatives as a single isomer.