Development of Asymmetric Cyclopentane Annulation Utilizing the Characteristics of Heteroatoms

研究了由我们小组开发的使用β-杂原子取代的丙烯酰基硅烷的[3 + 2]成环的不对称版本的扩展。丙烯酰硅烷，轴承的光学活性恶唑啉基甲硫基在其β-位置，与锂烯醇化的烷基甲基酮反应，得到可分离的非对映异构体环戊烯醇在可接受的非对映选择性。环戊烯醇可以转化为对映体纯的4-羟基环戊烯酮，这是具有生物活性的前列腺素类化合物的基本结构。以金雀花碱和双恶唑啉衍生物为手性配体，催化不对称[3 + 2]成环反应是可能的，但对映体过量值并不高，该反应已成功地应用于抗肿瘤海洋前列腺素clavulone II和clavulone III的合成。我们发现了一种有效的和立体定向的[3 + 4]成环，其通过使用（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的组合来实现，以直接的方式提供了新的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.