Hypervalent Iodine(III) Reagent Mediated Synthesis of Heterocycles

• Main Authors: Iou-Jiun Kang, 康祐竣
• Other Authors: Ling-Ching Chen
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/60798122509855669779

博士 === 高雄醫學大學 === 藥學研究所 === 91 === 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.