(一.) 經有機鹼催化調控區域選擇性Aza-1,4-/類Aza-1,6-加成之連續反應合成螺環/三取代四氫喹啉衍生物 (二.) 經分子內威悌反應合成螺環吡唑啉酮與1H-㗁呯[2,3-c]吡唑之衍生物

I. Base-controlled Catalytic Regioselective Aza-1,4/Formal Aza-1,6-addition Cascade Reaction for the Synthesis of Tetrahydroquinoline. II. Synthesis of Spiropentadiene Pyrazolones and 1H-Oxepino[2,3-c]pyrazoles from α,β,γ,δ-unsaturated Pyrazolones via Intramolecular Wittig Reaction

林藝芳(Lin Yi-Fang)

指導教授 ： 林文偉

國立臺灣師範大學/理學院/化學系/碩士(2021年)

https://doi.org/10.6345/NTNU202100782

摘要

(一). 本論文第一部分利用了對亞甲基苯醌及1,3-茚二酮衍生物經不同的鹼催化系統良好的控制其區域選擇性，使其合成出有良好產率的兩種具有不同骨架之四氫喹啉衍生物。透過4-二甲氨基吡啶 (DMAP) 可經過aza-1,4-加成/1,6-加成合環後得到具有螺環結構之四氫喹啉衍生物；而當使用四甲基胍 (TMG) 進行反應時，則會先得到1,4-加成後的產物，再經過重排/vinylogous 1,6-加成後得到(4+2)環加成之三取代四氫喹啉衍生物。
(二). 本論文第二部分利用α, β, γ, δ -不飽和吡唑啉酮 (α, β, γ, δ -Unsaturated Pyrazolones) 作為起始物，在經過取代基之立體效應、反應溶劑及反應條件的優化後，可以經由化學選擇性來得到不同的產物。反應經膦-1.6-加成/氧-醯化反應後生成七元環的betaine中間體，而其中當使用的取代基立體障礙較大時，可直接進行分子內威悌反應得到七元環–1H-㗁呯[2,3-c]吡唑衍生物。但當取代基上的立體障礙較小時，則會進行δ-碳-醯化/環化/分子內威悌反應而得到五元環–螺環吡唑啉酮衍生物，此兩種產物皆可在溫和的條件得到良好的產率及選擇性，並具有良好的官能基耐受性。

關鍵字

有機鹼催化 ； 區域選擇性 ； 四氫喹啉衍生物 ； 化學選擇性 ； 分子內威悌反應 ； 磷-1,6-加成 ； δ-碳-醯化

並列摘要

I. We developed a strategy for the regioselective synthesis of two different skeletons of tetrahydroquinoline derivatives by using para-quinone methide and 1,3-indandione derivatives under organobase catalysis. In the reaction condition using dimethylaminopyridine (DMAP) as the catalyst, the reaction underwent smoothly via aza-Michael addition/1,6-addition to obtain spirotetrahydroquinoline products. While 1,1,3,3-Tetramethylguanidine (TMG) was employed as the catalyst, it will generate the 1,4-addition product first, then underwent rearrengment/vinylogous 1,6-addition to obtain trisubstituted tetrahydroquinoline. Both of these two pathways achieved moderate to good yields and good regioselectivities.
II. We developed an efficient method for the synthesis of spiropentadiene pyrazolones and 1H-oxepino[2,3-c]pyrazoles in good to excellent yield. The methodology attributes O-acylation of phosphorus zwitterions which were formed by a tandem phospha-1,6-addition of PBu3 to α,β,γ,δ-unsaturated pyrazolones, further generating betaine intermediates that preferentially resulted in the aforementioned cyclic products in a diversity-oriented manner. When the highly steric hindered were employed, oxepino pyrazole derivatives were afforded as major products. On the contrary, spiropentadiene pyrazolone derivatives will be selectively provided. Mechanistic investigations revealed that formation of the betaines is the key step to provide the products via an intramolecular Wittig reaction or an unprecedented δ-C-acylation/cyclization/Wittig reaction.

並列關鍵字

Organobase Catalysis ； Regioselective ； Tetrahydroquinoline Derivatives ； Chemoselective ； Intramolecular Wittig Reaction ； Phospha-1,6-Addition ； δ-C-Acylation

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