Development of Asymmetric Cyclopentane Annulation Utilizing the Characteristics of Heteroatoms

利用杂原子特性开发不对称环戊烷环化

• 批准号: 06672091
• 负责人: TAKEDA Kei
• 金额: $ 1.34万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672091/
• 关键词: Cyclopentane annulation; [3+2] Annulation; Asymmetric synthesis; Catalytic asymmetric synthesis; 0rostanoids; Clavulones; 抗腫瘍性プロスタノイド; [3+2]付加環化反応; 不斉シクロペンタンアニュレーション; Brook転位; アシルシラン

An extension of the [3+2] annulation using beta-heteroatom-substituted acryloylsilanes developed by our group to an asymmetric version was investigated. Reaction of acryloylsilanes, bearing an optically active oxazolinylmethylthio group at their beta-position, with lithium enolate of alkyl methyl ketones afforded separable diastereomeric cyclopentenols in acceptable diasteroselectivities. The cyclopentenol could be transformed into enantiomerically pure 4-hydroxycyclopentenone, a basic structure in biologically active prostanoids. Catalytic asymmetric [3+2] annulation using commercially available chiral ligands such as sparteine and bisoxazoline derivatives proved possible although the observed enantiomeric excess was not high yet.This annulation has been successfully applied to the syntheses of clavulone II and clavulone III which is antitumor marine prostanoids.In the course of the study on the cyclopentane annulation, we discovered an efficient and stereospecific [3+4] annulation, which has been achieved by using (E)-(beta-(trimethylsilyl) acryloyl)-silane in combination with alkenyl methyl ketone enolate, affording novel, highly functionalized cycloheptenones in a straightforward manner.

研究了我们小组开发的使用β-杂原子取代的丙烯酰硅烷将[3+2]环化扩展到不对称版本的情况。在其β位带有光学活性恶唑啉基甲硫基的丙烯酰基硅烷与烷基甲基酮的烯醇锂反应，以可接受的非对映选择性提供可分离的非对映异构体环戊烯醇。环戊烯醇可以转化为对映体纯的 4-羟基环戊烯酮，这是生物活性前列腺素的基本结构。尽管观察到的对映体过量还不高，但使用市售手性配体（例如金雀花和双恶唑啉衍生物）进行催化不对称[3+2]环化被证明是可能的。该环化已成功应用于抗肿瘤海洋药物克拉维酮II和克拉维酮III的合成在环戊烷成环的研究过程中，我们发现了一种高效且立体定向的[3+4]环化，这是通过使用(E)-(β-(三甲基甲硅烷基)丙烯酰基)-硅烷与烯基甲基酮烯醇化物组合实现的，以简单的方式提供新型、高度官能化的环庚烯酮。