一、酸輔佐帶官能基環己-2-烯-1-醇分子內環化反應—雜環化合物的合成。二、鹵化銦輔佐烯炔醯胺環化反應。
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2015
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論文分為四個主題，主要利用布忍斯特酸或路易士酸對有機環氧基醇、環丙烷基醇、烯丙醇及烯炔醯胺官能基進行分子內環化反應，以合成含有雜原子的螺旋雙環化合物或稠環化合物。
第一章以間氯過氧苯甲酸輔佐3號位上帶有醯胺基、酯基側鍊的環己-2-烯-1-醇化合物，進行一鍋化的環氧化/螺旋雙環內酯化反應。形成帶有鄰位順式雙醇官能基的螺旋雙環內酯化合物。將3號位帶有酯基側鍊的環己-2-烯-1-醇化合物進行環氧化反應，接著將酯基進行水解形成羧酸鹽類後，再進行螺旋雙環內酯化反應，合成出相同的合環產物。證實以醯胺基取代進行合環反應並不會得到螺旋雙環內醯胺化合物，而是得到螺旋雙環內酯化合物。
第二章以三號位帶含炔丙基胺側鏈之環己-2-烯-1-醇，與二乙基鋅和二甲基碘在溶劑為二氯甲烷與乙醚的條件下，進行環丙烷化的反應。再利用所得到的三號位帶有炔丙基胺側鏈之雙環[4.1.0]庚烯類化合物，與1.2當量之三氯化鐵在室溫下反應，可在數分鐘內進行擴環、環化、氯化反應。合成含氮螺旋雙環[4.6]十一烯衍生物。以三溴化鐵亦可以進行類似的反應，得到含氮螺旋雙環[4.6]十一烯類的溴化物。
第三章以4號位上含有順式的3-芳香基炔丙基胺側鏈環己2-烯-1醇化合物，與催化量的三苯基膦氯金和六氟化鍗銀反應，使羥基行 9-endo-dig 反應對被金離子活化的炔基進行反式加成。接著產生克萊森重排反應，再經由互變異構化合成ㄧ組六氫吲哚的酮類衍生物。其差向異構物(epimer)可在氫氧化鉀的鹼性條件下進行差向異構化，而得到熱力學穩定的單一異構物。
第四章以1,5-烯炔醯胺化合物與三鹵化銦，進行5-exo-dig的分子內合環反應，可以合成1號位上有三鹵化甲基取代之含氮的茚化合物。若以3-苯基炔丙基磺醯胺化合物作取代甲基磺醯胺與三氯化銦反應，則會進行兩次合環反應、鹵化反應，生成茚并吡啶化合物。
Chapter I, spirolactones containing a vicinal cis-diol adjacent to the spiro-carbon center are prepared by one-pot epoxidation/spirocyclization of cyclohex-2-en-1-ols bearing an ester or amide functional side chain at the C(3) position of the ring. Since both C(3)-ester- and amide-tethered cyclohex-2-en-1-ols generated the same spirolactone, it can be stated that amide side chains underwent hydrolysis to give the corresponding spirolactone. Chapter II, the starting N-tosyl-N-(3-arylpropargyl)-tethered- 6-methylbicyclo[4.1.0]heptan-2-ols were prepared from cyclopropanation of the N-tosyl-N-propargyl-tethered 3-methylcyclohex-2-en-1-ols with the Furukawa-modified Simmons−Smith reagent. FeCl3-promoted ring expansion/cyclization/chlorination of N-tosyl-N-(3-arylpropargyl)-tethered- 6-methylbicyclo[4.1.0]heptan-2-ols afforded the 2-azaspiro[4.6]-undec-7-ene rings. Iron tribromide also performed well to generate the 2-aza-4-(bromomethelene)spiro[4.6]-undec-7-ene compounds under the same reaction conditions. Chapter III, cis-4-[N-tosyl-N-(3-arylprop-2-ynyl)amino]cyclohex- 2-en-1-ols were cycloisomerized with a catalytic amount of chloro(triphenylphosphine)gold(I) and silver(I) hexafluoroantimonate. The cyclization is proposed to proceed via a 9-endo-dig attack of the hydroxyl group onto the gold-activated alkyne. The resulting allyl vinyl ether intermediate underwent a gold-assisted Claisen-type rearrangement to form 3-exo and 3-endo-3-aroylhexahydroindole derivatives. Treatment of the crude mixture with base provided only 3-exo-aroylhexahydroindoles in good yields and complete stereoselectivity. Chapter IV, a 5-exo-dig cyclization of 1,5-enynamide with indium(III) chloride provided trichloromethyl substituted 2-aminoindene derivatives. Reaction of N-((2-(2,2-dihalovinyl)phenyl)ethynyl)-4-methyl-N-(3-phenylprop- 2-yn-1-yl)benzene-sulfonamides with indium(III) halide generated a tandem cyclizations/halogenation to construct indeno[2,1-b]pyridines.
Chapter I, spirolactones containing a vicinal cis-diol adjacent to the spiro-carbon center are prepared by one-pot epoxidation/spirocyclization of cyclohex-2-en-1-ols bearing an ester or amide functional side chain at the C(3) position of the ring. Since both C(3)-ester- and amide-tethered cyclohex-2-en-1-ols generated the same spirolactone, it can be stated that amide side chains underwent hydrolysis to give the corresponding spirolactone. Chapter II, the starting N-tosyl-N-(3-arylpropargyl)-tethered- 6-methylbicyclo[4.1.0]heptan-2-ols were prepared from cyclopropanation of the N-tosyl-N-propargyl-tethered 3-methylcyclohex-2-en-1-ols with the Furukawa-modified Simmons−Smith reagent. FeCl3-promoted ring expansion/cyclization/chlorination of N-tosyl-N-(3-arylpropargyl)-tethered- 6-methylbicyclo[4.1.0]heptan-2-ols afforded the 2-azaspiro[4.6]-undec-7-ene rings. Iron tribromide also performed well to generate the 2-aza-4-(bromomethelene)spiro[4.6]-undec-7-ene compounds under the same reaction conditions. Chapter III, cis-4-[N-tosyl-N-(3-arylprop-2-ynyl)amino]cyclohex- 2-en-1-ols were cycloisomerized with a catalytic amount of chloro(triphenylphosphine)gold(I) and silver(I) hexafluoroantimonate. The cyclization is proposed to proceed via a 9-endo-dig attack of the hydroxyl group onto the gold-activated alkyne. The resulting allyl vinyl ether intermediate underwent a gold-assisted Claisen-type rearrangement to form 3-exo and 3-endo-3-aroylhexahydroindole derivatives. Treatment of the crude mixture with base provided only 3-exo-aroylhexahydroindoles in good yields and complete stereoselectivity. Chapter IV, a 5-exo-dig cyclization of 1,5-enynamide with indium(III) chloride provided trichloromethyl substituted 2-aminoindene derivatives. Reaction of N-((2-(2,2-dihalovinyl)phenyl)ethynyl)-4-methyl-N-(3-phenylprop- 2-yn-1-yl)benzene-sulfonamides with indium(III) halide generated a tandem cyclizations/halogenation to construct indeno[2,1-b]pyridines.
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螺旋化合物, 環氧化反應, 內酯化反應, 三氯化鐵, 環丙烷化反應, 擴環反應, 六氫吲哚, 金催化反應, 克萊森重排反應, 三鹵化銦, 炔醯胺化合物, 胺基茚化合物, 茚并吡啶化合物, spiro compound, epoxidation, lactonization, iron(III) chloride, cyclopropanation, ring expansion reaction, hexahydroindole, gold(I) catalyzed, Claisen rearrangement, indium(III) halide, ynamide, aminoindene, indeno[2, 1-b]pyridine