Nucleophilic anti-Michael Addition of Phosphines and Amines to Enynedioates and Oligoynoates: Fluorescent γ-Lactones, γ-Lactams, Drug Precursors 3-Phosphorus Oxindoles and Trisubstituted Furans via Three-Component Reactions

Abstract

在本論文中，我們發現以三級膦作親核加成在炔基酯上時，會行麥可與反麥可親核加成反應。在丁炔二酸二甲酯 (DMAD)、三芳香基膦與缺電子的苯基醛反應中，經由麥可加成 (Michael addition) 可生成高產率的伽瑪-環內酯 (γ-lactone)，此外，在三烷基膦作親核試劑的反應中，經由穩定磷基烯醇中間體所形成的伽瑪-環內酯則可當作Wittig試劑與缺電子的苯基醛反應，得到產率不錯的烯基伽瑪-環內酯。伽瑪-環內酯與伽瑪-內醯胺 (γ-lactam) 亦可由三級膦經反麥可加成 (anti-Michael addition) 至共軛炔基酯之反應中獲得，而這些五圓雜環分子擁有從未被報導過的高度螢光性質。由於它們的重要性與創新性，我們測量每個分子之螢光量子產率與電腦計算其前沿分子軌域 (frontier orbital)。 Dimethyl (E)-hex-2-en-4-ynedioate可與一級胺、二級胺行反麥可加成生成α,β脫氫胺酯之衍生物 (α,β-dehydroamino acid derivatives)，也可與三級膦及α,β-不飽和亞胺醛產生具有三個連續烯基的伽瑪-內醯胺，而此內醯胺可經由照光及加熱進行6π-電子環化反應產生氧化吲哚 (oxindole)。這些在3號碳上有三級膦的氧化吲哚伊立德 (ylide) 可使用適當當量的間氯過氧苯甲酸 (mCPBA) 將其氧化為2,3-吲哚二酮 (isatin) 與 isoxazolinone。最後，三級膦、缺電子苯基醛與對稱雙缺酯 (symmetric diyndioate) 所產生之三取代呋喃伊立德除了可和苯基醛行Wittig反應將三級膦置換生成烯類化合物外，也可使用適間氯過氧苯甲酸將碳磷雙鍵氧化為碳氧雙鍵。這些結構可透過氫、碳、磷核磁共振儀、紅外線光譜儀、高解析質譜儀以及X光單晶繞射儀來分析並確定其正確結構。

In this content, we have provided a full investigation of the normal and abnormal addition pattern of phosphines to substituted ynoates. The reaction of DMAD, arylphosphines and benzaldehydes could give γ-lactone bearing α-phosphorus ylides in good yields. The γ-lactones synthesized by alkyphosphines, through stable tetravalent phosphonium enolate zwitterions as intermediates, could react with aldehydes to give olefinic γ-lactones via Wittig reaction in moderate yields. The γ-lactones and γ-lactams could be synthesized by first anti-Michael or α(δ')-addition of phosphines to enynedioates as well. These five-membered heterocyclics, on the other hand, possessed strong fluorescent emissions that never reported as chromophores before. As a result, due to their novalty and importance, we also synthesized and investigated the fluorescent properties and computational data of the oligoynoates derived γ-lactones. The anti-Michael or α(δ')-addition of dimethyl (E)-hex-2-en-4-ynedioate could also be utilized to give α,β-dehydroamino acid derivatives and 3-phosphorus oxindoles via 6π electrocyclization. The oxindoles could be further oxidized with appropriate amount of mCPBA and workup process to give isatins and isoxazolinones in moderate to excellent yields. Finally, we also synthesized trisubstituted furan with the reaction of diynedioates, phsophines and aldehydes via cumulated trienoates as key step. The resulting phosphorus furan could be oxidized to α-keto ester furans and utilized as Wittig reagents.