(一) 經有機膦試劑催化直接型 β 位醯化反應建構官能化 2-亞芳基羥吲哚化合物(二) 經分子內威悌反應合成螺環羥吲哚和環戊二烯[b]吲哚之衍生物(三)多樣性導向策略經有機鹼調控合成螺環/三取代四氫喹啉衍生物

Abstract

(一) 在過去，有機催化量磷烷反應在有機合成中無所不在，具有構建多樣天然活性分子的巨大潛力。膦試劑廣泛應用於建構碳碳鍵和雜環分子。我們利用環狀查爾酮骨架分子-吲哚酮作為起始物，可在吲哚酮親電子性質的β位直接進行醯化反應。除了產物外，此部分的另一重點在於對於線型和環狀查爾酮在膦試劑催化反應中結果觀察在此研究中發現線性查爾酮傾向形成威悌產物，環狀查爾酮則傾向生成β醯化產物。(二) 在此部份我們發展出以多樣性導向合成螺戊二烯二氫吲哚和苯基環戊二烯[b]吲哚的方法。在此部分的研究中利用膦試劑先形成膦兩性離子在含有醯氯的環境底下進行氧醯化反應為關鍵步驟。此一反應由膦試劑進行1,6-加成反應來啟動，接續的反應過程中生成關鍵的betaine七元環中間體，隨後的開環/δ-C-醯基轉移/環化/分子內威悌反應，即可得螺戊二烯二氫吲哚產物；在反應中，我們發現另一產物苯基環戊二烯[b]吲哚衍生物，根據結果結構推測在前期膦試劑的加成具有選擇性，透過添加時間的控制，可有效的使膦試劑進行1-4,加成反應，並進行β-C-醯基轉移/環化/分子內威悌反應。(三) 多樣性導向已成為建構複雜分子的通用、快速和選擇性的合成策略，廣泛用於藥物開發。過去，我們發現基於催化劑的多樣性導向策略用於建後生物學重要的化合物，讓我們對多樣性導向有延伸興趣。我們希望報導一種新穎且有效的有機鹼控制方法，用於製備螺氫喹啉-茚二酮和 3-亞甲基氫喹啉-茚二酮衍生物。DMAP控制進行aza-1,4-麥克/1,6-加成/級聯反應，將鄰甲苯磺醯氨基苯基取代的對醌甲基化合物加成到芳基烯丙基-茚滿二酮中主要產生螺氫喹啉-茚滿二酮產物。或者，使用TMG作為鹼試劑時，觀察到亞甲基氫喹啉-茚滿二酮衍生物的選擇性形成。控制實驗和機制研究表明，在TMG系統中，生成了作為中間體的螺氫喹啉-茚滿二酮，進一步經歷了逆向1,6-加成/1,3-sigmatropic重排/vinylogous 1,6-加成序列獲得亞甲基氫喹啉-茚滿二酮。也可一鍋化、克級反應和其他雜芳基烯基底物。

1.Organophosphane-catalyzed reactions are ubiquitous in organic synthesis because of their high potential to construct a variety of natural products and wide range of biologically active molecules. Phosphine-mediated or –catalyzed reactions are widely used in the construction of carbon-carbon bonds and heterocyclic molecules. We report an efficient, direct β-acylation method utilizing acyl chlorides and the enones with the indolin-3-one moiety as the substrates. In addition, results indicated that the reported linear chalcone derivatives as substrates tend to form the Wittig products, whereas five-membered cyclic chalcone derivatives tend to form β-acylation products.2.An sufficient method for the diversity-oriented synthesis of spiropentadiene indoline and phenylcyclopenta[b]indole is reported. The reaction attributes O-acylation of phosphorus zwitterions which were formed by a tandem phospha-1,6-addition of PBu3 to α,β,γ,δ-unsaturated oxindole, further generating betaine intermediates that preferentially resulted in the aforementioned cyclic products in a diversity-oriented manner. The 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. On the other hand, regioselective phospha-1,4-addition of PBu3 to α,β,γ,δ-unsaturated oxindole, generated betaine intermediates which furnished different cyclic products. The reaction is believed to proceed via the phospha-1,4-addition, an unprecedented β-C-acylation, the second phospha-1,4-addition, and the intramolecular Wittig reaction.3.The diversity-oriented synthesis (DOS) has been emerged as versatile, rapid and selective strategy for the synthesis of structurally complex molecules, and it is widely employed in pharmaceutical drug discovery. Previously we have discovered catalyst-based DOS approach to construct diverse biologically important compounds. In continuation of our interst in DOS, we wish to report an novel and efficient organobase-controlled method for the preparation of spirohydroquinoline-indanedione and 3-methylenehydroquinoline-indandione derivatives. The 4-dimethylamino pyridine (DMAP) controlled cascade reaction proceeds via aza-Michael/1,6-addition of ortho-tosylaminophenyl-substituted para-quinone methides to the arylallylidene-indanediones, which predominantly resulted the spirohydroquinoline-indanedione product. Alternatively, when 1,1,3,3-tetramethylguanidine (TMG) was employed as a base, selective formation of the methylenehydroquinoline-indandione derivatives were observed. The control experiments and mechanistic study revealed that, under the influence of TMG, the spirohydroquinoline-indanedione as an intermediate was generated, which further underwent the retro 1,6-addition/1,3-sigmatropic rearrangement/vinylogous 1,6-addition sequence to access the methylenehydroquinoline-indandiones. Additionally, this protocol could be applicable in one-pot operation, gram scale synthesis and the extension to other heteroarylallylidene substrates.