The First Spiro Isoxazoline Ligands

在从头计算的基础上，我们对异恶唑啉的螯合能力产生了极大的兴趣。在本项目中，我们设计并合成了第一个含有刚性螺环骨架的手性双(异恶唑啉)配体(SPRIX)。配体对Pd(II)盐表现出很强的亲和力，由此得到的手性Pd(II)-螺环双(异恶唑啉)催化剂促进了烯醇的不对称Wacker环化反应。此外，还研究了二烯醇催化不对称串联环化反应，一步合成了一种独特的双环醚，ee可达95%。合成了新型的双(异恶唑啉)配体2，2‘-双(异恶唑啉)丙烷和(R)-2，2’-双(异恶唑啉)-1，1‘-联萘，在Pd(II)催化的烯醇Wacker环化反应中表现出较强的配体加速效应。恶唑啉配体的无加速效应清楚地表明了异恶唑啉部分在烯醇的Wacker环化反应中的关键作用。在一氧化碳存在下，Pd(II)-螺环双(异恶唑啉)催化剂还能促进烯胺或醇的不对称羰化反应，得到具有中等对映体选择性的吡咯烷或内酯。

We had great interest in the chelating ability of isoxazolines on the basis of ab initio calculations. In this project, we have designed, and synthesized the first chiral bis(isoxazoline) ligands (SPRIXs) containing rigid spiro skeleton. The ligands showed great affinity towards Pd(II) salts and the resulting chiral Pd(II)-spiro bis(isoxazoline) catalysts promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols. Furthermore, a new catalytic asymmetric tandem cyclization of dialkenylalcohol took place, affording a unique bicyclic ether in one step with up to 95% ee. New type of bis(isoxazoline) ligands, 2,2'-bis(isoxazolinyl)propane and (R)-2,2'-bis(isoxazolinyl)-1,1'-binaphthyl have been prepared and strong ligand-acceleration effects were demonstrated in Pd(II)-catalyzed Wacker-type cyclization of alkenyl alcohol. The lack of acceleration effects with oxazoline ligands clearly shows the crucial role of isoxazoline moiety on the Wacker-type cyclization of alkenyl alcohols. In the presence of carbon monoxide the Pd(II)-spiro bis(isoxazoline) catalyst also promoted the asymmetric carbonylation of alkenyl amines or alcohols to give pyrrolidines or lactones with moderate enantioselectivities.