Development of a General Method for Synthesis of Optically Active Tertiarv Allylic Alcohols and Its Applications

叔烯丙醇存在于各种天然产物和具有重要商业价值的药物的结构中。同样重要的是，叔烯丙醇作为多功能合成中间体具有潜在的功能。然而，只有少数几种方法可用于手性形式的制备，这些方法存在光学纯度低和/或缺乏通用性等缺点。目前，我们已经成功地开发了一种实用、通用的叔烯丙醇的合成方法，利用伽马-三甲基硅基-α，β-环氧基丙酮与格氏试剂的非对映选择性反应，合成了旋光性很强的γ-三甲基硅基-α，β-环氧叔醇。伽马-三甲基硅基-β，伽马-环氧叔醇与亲核试剂反应，通过区域特异性开环和Peterson烯化反应得到相应的叔烯丙醇。将得到的叔烯丙醇应用于前列腺素衍生物Arbaprostil的合成。

Tertiary allylic alcohols are incorporated in the structures of a variety of natural products and commercially important pharmaceuticals. Equally significant is the latent faculties of tertiary allylic alcohols as versatile synthetic intermediates. Only a few methods, however, are available for preparation of them in a chiral form and these methods so far developed suffer from some disadvantages such as low optical purity and/or lack of generality. We have now succeeded in developing practical and general synthetic method of tertiary allylic alcohols.Thus, the reaction of beta-trimethylsilyl-alpha, beta-epoxyketones, readily prepared in a chiral form by using the Sharpless kinetic resolution of gamma-trimethytsilyl secondary allylic alcohols as a key reaction, with Grignard reagents proceeds highly diastereoselectively to afford optically active gamma-trimethylsilyl-beta, gamma-epoxy tertiary alcohols. gamma-Trimethylsilyl-beta, gamma-epoxy tertiary alcohols reacts with nucleophils affords the corresponding tertiary allylic alcohols via regionspecific ring opening followed by the Peterson olefination reaction. The application of the tertiary allylic alcohols thus obtained to the synthesis of prostaglandin derivative, Arbaprostil was carried out.