Creation of C2-Symmetric Molecules using An Asymmetric Dihydroxylation and Its Application

由于手性C2对称分子在不对称合成中起着重要的作用，其不对称合成越来越受到人们的关注。我们描述了一条合成C2对称四醇的有希望的路线，该路线涉及对称末端双烯的夏普莱斯不对称二羟基化反应(AD)及其在合成C2对称手性胺方面的应用，C2对称手性胺是广泛使用的手性助剂的代表。Sharpless小组建立的先例表明，对于末端烯烃来说，对映体过量可能是适度的(或多或少80%ee)。在对称双烯中，如双烯烃连结，我们预计基于以下考虑可以提高立体选择性：第一个AD反应产生主要和次要的对映体(二醇)。由于每个对映体都经历了与第一次AD反应基本相同的第二次AD反应，产生了三个四醇产物：C2对称化合物1、介孔化合物1和Et-1。总的结果是，由不希望发生的对映面攻击引起的大部分AD反应都会导致介观化合物。只有很少的镜像化合物ENT-1生成，因此主要的C2对称产物1的对映体纯度将较高。基于这些考虑，从双烯(1，5-己二烯、1，6-庚二烯和烯丙基醚)中确实合成了高对映体纯度的C_2对称叔醇。随后，四元醇被转化为C2对称的欧米克保护的α，α‘-双羟甲基吡咯烷，哌啶和吗啡。有趣的是，我们发现在硅胶上的中压层析对吡咯烷和哌啶类化合物具有适度的对映体选择性，导致了高效的对映体分离。

Since chiral C_2-symmetric molecules play an important role in an asymmetric synthesis, much attention has increasingly been focused on their asymmetric synthesis. We describe a promising route to C_2-symmetric tetraols involving the Sharpless asymmetric dihydroxylation (AD) of symmetric terminal dienes and its application to the synthesis of C_2-symmetric chiral amines the representative of chiral auxiliaries of wide use.The precedent established by the Sharpless group suggested that enantiomeric excess in the case of terminal olefins might be modest (more or less 80% ee). In a symmetrical diene such as the twin olefins conjoined, we anticipate that the stereoselectivity might be improved based on the following consideration : The first AD reaction produces the major and minor enantiomers (diols). Since each enantiomer undergoes the second AD reaction with essentially the same enantiofacial selectivity as in the first AD reaction, three tetraol products result ; a C_2-symmetry compound 1, a meso compound, and ent-1. The overall consequence is that most of the AD reaction resulting from the undesired enantiofacial attack leads to the meso compound. Very little of the mirror image compound ent-1 is formed, and therefore the enantiomeric purity of the major C_2-symmetry product 1 will be high. Based on these consideration, the C_2-symmetric teraols are prepared indeed in high enantiomeric purities from dienes (1,5-hexadiene, 1,6-heptadiene, and ally1 ether). Subsequently, the tetraols are transformed into C_2-symmetric OMICRON-protected alpha, alpha'-bishydroxymethylpyrrolidines, piperidines, and morphorine. Interestingly, we found that medium-pressure chromatography on silica gel of pyrrolidines and piperidines with modest enantioselectivity resulted in efficient enantiomeric fractionation.