Development and Application of <C_2> -Symmetrically Substituted Pyrrolidine Chiral Auxiliaries

研究了以2，5-二取代吡咯烷为手性助剂的不对称反应及相关的立体选择性反应，发现在相应的烯醇化锆催化下，酰胺烯醇化物与醛的羟醛缩合反应具有高的非对映选择性（>60：1）和非对映选择性（>95% de）。（E）-烯氧基乙酰胺衍生的烯醇化锆在[2，3]Wittig重排反应中表现出高水平的顺式-非对映体（>28：1）和非对映体（> 95%de）选择性。锆介导的（E）-β-烯氧基乙酸酯的[2，3]Wittig重排<alpha>也以顺式非对映选择性（&gt;50：1）、高水平的手性转移（~ 100%）和排他性的（Z）-双键的形成进行。这种[2，3]Wittig重排反应和Peterson反应的组合提供了一种高度立体选择性的方法来制备（E，Z）-和（Z，Z）-二烯。此外，锆介导的烯醇化物Claisen重排反应是通过船状过渡态进行的，不同于通常的[3，3] σ迁移重排反应通过椅状过渡态进行，其中一些反应被应用于天然产物的合成。通过这些研究获得的信息被认为有助于发展无环立体控制。

Effective asymmetric reactions with 2,5-disubstituted pyrrolidines as chiral auxiliaries and related stereoselective reactions were developed.The aldol condensation of the amide enolates derived from these amides, with aldehydes proceeded with high diastereo (>60:1) and diastereoface (>95% de) selectivities, when the corresponding zirconium enolates were used. Zirconium enolates derived from (E)-alkenyloxyacetyl amides, exhibited high level of syn-diastereo (>28:1) and diastereoface (>95% de) selectivities in their [2,3]Wittig rearrangement reaction. Zirconium mediated [2,3]Wittig rearrangement of (E)- <alpha> -alkenyloxyacetic acid esters was also performed with syn-diastereoselectivity (>50:1), high level of chirality transfer (-100%), and exclusive formation of (Z)-double bond. A combination of this [2,3]Wittig rearrangement reaction and Peterson reaction provided a highly stereoselective approach to (E,Z)- and (Z,Z)-dienes. Further, zirconium mediated enolate Claisen rearrangement was found to proceed through a boat-like transition state, differing from the usual [3,3]sigmatropic rearrangements which proceed through a chair-like transition state.Some of these reactions were applied to the synthesis of natural products. Informations obtained through these studies are considered to contribute to the development of acyclic stereocontrol.