Studies on a Novel Dehydrationg Gent, (Trimethylsilyl)ethoxyavetylene

我们发现，在温和的条件下，(三甲基硅基)乙氧基乙酸乙酯(TMEA)为包括酸敏感的羧酸在内的各种类型的羧酸的脱水提供了一种非常有效的方法，并且可以很容易地分离出纯产物。这些羧酸酐被成功地用于强碱诱导的环加成反应，生成了蒽环类化合物。我们还成功地将这种羧基活化法应用于酰胺的合成。我们首次通过TMEA的强碱诱导环加成反应合成了柔红霉素的D-环噻吩基和吲哚类似物。该试剂，TMEA被发现不仅对酰胺的形成有用，而且对Eewster、内酯或非外消旋的多肽的形成也有用。然后，我们发现了TMEA减压加热容易制备的特甲基硅基酮(TIMK)，它与不同类型的醇反应得到1，2加成产物α-三甲基硅基乙酸酯。分子中含有羰基的醇类似地与TMSK反应生成相应的-lt；α&gt；-(三甲基硅基)乙酸酯，该反应高产率地与5-不饱和内酯发生Pererson反应。现在，我们试图寻找一种新的反应，使用各种类型的-lt；α&gt；-(三甲基硅基)乙酸酯，通过用TM K处理具有某些活性官能团的醇而得到。

We have found that (trimethylasilyl)ethoxyacetlene (TMEA) provided a quire effective method for dehydration of various types of carboxylic acids, including acids-sensitive catboxylic acide into the corresponding carboxylic anhydrides under nmild conditions, and allowed easy isolation of pure products. These carboxylic anhydrides were successfully utilized for the strong base-induced cycloaddition to naphthoquinones leading to anthracyclines. We also succeeded in applying this carboxyl group activating method to the synthesis of amides.The following progress was made in the present project. We suvveeded in the first total sysnthesis of D-rind thiophene and indole analogues of daunomycin via a stronf-base induced cycloaddition of hterohomophthalic anhydride obtained by the use of TMEA. The reagent, TMEA was found to useful not only for amide formation but also for ewster, lactone, or non-racemized peptide formation. Next, we founs thar teimethylsilyl ketene (TMSK), readily prepared by heating of TMEA under reduced pressure, reacted with vatious types of alconhols to give the 1,2addition products, a-(trimethylsilyl)acetates in quantitative yield. The alcohol having carbonyl group in the moleuce similarly reacted with TMSK to give the corresponfding <alpha>-(trimethylsilyl)acetate, which caused an intramolcular pererson reaction to five <alpha>,<beta>-unsaturated lactone in excellent yield. We now try to find a novel annelation reaction using various types of <alpha>-(trimethylsilyl)acetates obtained by treatment of alcohols having some active functional gqoup with TMSK.