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有效不对称反应及相关立体选择性反应。当使用相应的烯醇化锆时，由这些酰胺衍生的酰胺烯醇化物与醛的醛缩反应具有高的非映面选择性（>60:1）和非映面选择性（>95% de）。从(E)-alkenyloxyacetyl酰胺衍生而来的烯醇化锆在其[2,3]Wittig重排反应中表现出高水平的顺非对映面（>28:1）和非对映面（>95% de）选择性。锆介导的[2,3](E)- < α > - alkenyloxy乙酸酯的Wittig重排也具有同步非对映选择性（>50:1），高水平的手性转移（-100%）和(Z)-双键的排他性形成。这种[2,3]Wittig重排反应和Peterson反应的结合为（E，Z）-和（Z，Z）-二烯提供了高度立体选择性的方法。此外，锆介导的烯酸酯clisen重排通过船状过渡态进行，与通常的[3,3]符号位重排通过椅子状过渡态进行不同。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无环立体控制的发展。

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.