Development of Asymmetric Cyclopentane Annulation Utilizing the Characteristics of Heteroatoms

我们研究了用β -杂原子取代的丙烯基硅烷将[3+2]环化延伸到不对称的版本。丙烯基硅烷与烷基甲基酮的烯酸锂反应得到具有可接受的非对映体选择性的可分离的非对映体环戊烯醇。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。利用商业上可用的手性配体（如sparteine和bisoxazoline衍生物）催化不对称[3+2]环化证明是可能的，尽管观察到的对映体过量还不高。该环已成功应用于抗肿瘤海洋类前列腺素clavulone II和clavulone 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的立体定向环化[3+4]，该环化是通过(E)-（β -（三甲基硅基）丙烯酰）硅烷与烯烯基甲基酮烯醇酯结合而实现的，以一种简单的方式提供了新型的、高度功能化的环庚烯酮。

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.