Development of Asymmetric Cyclopentane Annulation Utilizing the Characteristics of Heteroatoms

研究了用本课题组开发的β-杂原子取代的丙烯酰基硅烷将[3，2]环化为不对称环化反应。丙烯酰基硅烷的β-位带有光学活性的恶唑啉甲硫基，与烷基甲基酮的烯酸锂反应，得到了具有可接受的非对映选择性的可分离的非对映异构环戊烯醇。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类化合物的基本结构。在环戊烷环化反应的研究中，我们发现了一种高效的、立体专一性的[3，4]环化反应，这种环化反应是通过(E)-(β-(三甲基硅基)丙烯酰基)硅烷与烯基甲基酮烯醇酸酯相结合实现的。

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.