- 學位論文
利用高價碘(III)試劑進行雜環的合成研究
Hypervalent Iodine(III) Reagent Mediated Synthesis of Heterocycles
摘要
近年來，由於高價碘試劑具有低毒性、易處理的特質，所以被廣泛地應用於有機合成上。而其中的phenyliodine(III) diacetate (PIDA)、phenyliodine(III) bis(trifluoroacetate) (PIFA)與[hydroxy(tosyloxy)iodo]- benzene (HTIB)是最常被使用的高價碘試劑。在本研究中，我們分別利用高價碘試劑PIDA與PIFA來進行雜環化合物的合成。 在一系列對高價碘化合物反應性的研究探討中，我們將高價碘化合物應用在下列四種反應上: Pummerer-type反應、 interrupted Pummerer-type反應、Pictet-Spengler縮合反應以及將aryl methyl ketones (48) 轉換成oxazoles (50)的反應。 由於(2E,4E)-不飽和醯胺類的piperidine、pyrrolidine和isobutylamine衍生物是具有殺蟲活性的天然物。在此，我們利用1-[(2-methylthio)ethanoyl]- piperidine (31)的Pummerer-type反應中間體32來跟1-alkenes反應，可以得到ene反應的附加體33。這種方法可以用來合成不飽和醯胺類天然物N-[(2E,4E)-decadienoyl]piperidine (34d)和N-[(2E,4E)-tetradecadienoyl]piperi- dine (34g)。 Isothiazol-3(2H)-ones在工業上的用途很多，而且具有抗菌、殺藻的活性。利用PIFA-TFA組合試劑與N-substituted (Z)-3-(benzylsulfanyl)propen- amides (37)反應，可經由interrupted Pummerer-type反應得到N-substituted isothiazol-3(2H)-ones。而不是一般Pummerer-type反應的產物。 Pictet-Spengler縮合反應在1,2,3,4-tetrahydroisoquinolines的合成上是一種很常見方法，利用PIFA和ethyl methylthioacetate進行Pictet-Spengler縮合反應的修飾時，對於苯環上含有去活化置換基的b-phenethylamines亦能順利進行環化反應，得到目的化合物ethyl 1,2,3,4-tetrahydroisoquinoline- 1-carboxylates (46)。 Oxazoles是synthetic transformations的有用出發物，而且是生理活性天然物的重要組成骨架。一般而言，直接利用ketones來合成oxazoles的方法並不是很多，在phenyliodine(III) triflate存在下，利用aryl methyl ketones與nitriles反應，能夠提供一個直接、有效的方法來合成2-substituted-5-aryl- oxazoles (50)。
並列摘要
In recent years, hypervalent iodine reagents have attracted much attention as useful synthetic reagents. These hypervalent iodine reagents have been extensively used in organic synthesis due to their low toxicity and easy handling. In the family of hypervalent iodine compounds, phenyliodine(III) diacetate (PIDA), phenyliodine(III) bis(trifluoroacetate) (PIFA) and [hydroxy(tosyloxy)- iodo]benzene (HTIB) are the most frequently used and easily available reagents. In this work, PIDA and PIFA have been applied to prepare heterocyclic compounds. As a series of studies on the reactions of the hypervalent iodine(III) compounds, four improved procedures for Pummerer-type reaction, interrupted Pummerer-type reaction, Pictet-Spengler condensation, and the conversion of aryl methyl ketones (48) to the corresponding oxazoles (50) are described. (2E,4E)-Unsaturated amides derived from piperidine, pyrrolidine and isobutylamine are interesting synthetic targets since they belong to an important class of natural products, which are common flavour constituents, and also show both physiological and insecticidal activities.The Pummerer-type reaction intermediate 32 of 1-[(2-methylthio)ethanoyl]piperidine (31) has been found to react with 1-alkenes to afford ene adducts 33. This methodology has been applied to the synthesis of naturally occurring unsaturated amides N-[(2E,4E)-decadienoyl]piperidine (34d) and N-[(2E,4E)-tetradecadienoyl]- piperidine (34g). Isothiazol-3(2H)-ones have found a range of industrial applications and are widely used as antimicrobial and algicidal additives. Treatment of N-substituted (Z)-3-(benzylsulfanyl)propenamides (37)with PIFA containing trifluoroacetic acid resulted in an interrupted Pummerer-type reaction to give N-substituted isothiazol-3(2H)-ones (38) rather than the normal Pummerer-type products. Pictet-Spengler condensation is one of the fundamental reactions for the preparation of 1,2,3,4-tetrahydroisoquinolines. We reported here a modified Pictet-Spengler cyclization of N-sulfonyl-b-phenethylamines with ethyl methylthioacetate using PIFA to prepare ethyl 1,2,3,4-tetrahydroisoquinoline- 1-carboxylates (46). Oxazoles are important constituent in biologically active natural products and served as versatile starting materials in synthetic transformations. Although many good general methods are available for the preparation of oxazoles, little has been known for synthesis of oxazoles from ketones. A direct and efficient method for the preparation of 2-substituted-5-aryloxazoles (50) was realized by reaction of aryl methyl ketones with various nitriles in the presence of phenyliodine(III) triflate.