烯炔醇合成2-亞苄基-3-吡咯啉之開發與其轉換

Abstract

多芳香取代1,4,3-烯炔醇化合物(I)可以簡單的由查爾酮製備，此骨架對酸具有高度的反應性，容易脫羥基生成高度共軛的碳陽離子。在路易士酸的存在下，親核性太弱的乙腈、三氟甲磺胺將無法捕捉此骨架的碳陽離子，其將會以自身做為親核基，發生二聚化反應，生成二烯二炔大型分子。使用親核性適當的甲苯磺胺，在硫酸的存在下將能夠有效的與1,4,3-烯炔醇進行取代反應，生成2,4,1-烯炔胺(II)。將此烯炔胺分子粗產物在未純化下，利用催化量醋酸銀與三苯基膦的搭配，在甲醇與二氯乙烷共溶劑中能夠有效的進行炔基活化反應，生成多芳香取代的2-亞苄基-3-吡咯啉(III)，在此催化條件下，合環反應後沒有自發地進行芳香化生成苄基吡咯(IV)。 在後續合成轉換的應用上，此具環外雙鍵的吡咯啉能與mCPBA反應，生成γ-內醯胺分子(V)，為合成二芳香取代α,β-不飽和內醯胺的方法之一，而異構後的吡咯則無法具有此反應活性。吡咯啉能夠在酸性環境下芳香化成吡咯，而在三氟化硼路易士酸的存在下，能夠更進一步進行甲苯磺基遷移，由N-甲苯磺基吡咯異構生成4-甲苯磺基吡咯(VI)。

1-En-4-yn-3-ol (I) can be easily synthesized from chalcone derivatives. This skeleton possesses a high reactivity toward acids and readily forms a highly conjugated carbocation through dehydration. Under Lewis acid conditions, nucleophile such as acetonitrile or trifluorosulfonamide is not able to trap the carbocation of enynol, but yielding a dimerized diendiyne product. Tosyl sulfonamide is found to be suitable for trapping the carbocation in the presence of sulfuric acid. The sulfonamide attacks at the secondary carbon site to form the 2-en-4-yn-1-amide skeleton (II) in a considerable yield. Without further purification, II undergoes 5-exo-dig alkyne cyclization reaction via the catalysis of silver acetate and triphenylphosphine to render 2-benzylidene-3-pyrroline (III) without the formation of any aromatized product 2-benzyl-pyrrole (IV). For the further synthetic transformations, mCPBA can react with the exocyclic double bond of 2-benzylidene-3-pyrrolines, resulting the C-C double bond cleavage, to furnish a α,β-unsaturated γ-lactam (V). 2-Benzyl-pyrroles IV can be easily generated from the aromatization of 2-benzylidene-3-pyrroline under acidic conditions. However, an unexpected tosyl migration was observed when 4-tosyl pyrrole (VI) was treated with boron trifluoride.