Development of Asymmetric Cyclopentane Annulation Utilizing the Characteristics of Heteroatoms

研究了我们小组开发的使用β-杂原子取代的丙烯酰基硅烷将[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（例如金雀花碱和双恶唑啉衍生物）进行催化不对称[3 2]环化已被证明是可能的。该环化已成功应用于抗肿瘤海洋前列腺素类化合物克拉维酮II和克拉维酮III的合成。在环戊烷环化的研究过程中，我们发现了一种高效且立体特异性的[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。

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.