Phosphoramidite Gold(I)-Catalyzed Diastereo- and Enantioselective Synthesis of 3,4-Substituted Pyrrolidines

In this article the utility of phosphoramidite ligands in enantioselective AuI catalysis was explored in the development of highly diastereo- and enantioselective AuI-catalyzed cycloadditions of allenenes. A AuI-catalyzed synthesis of 3,4-disubstituted pyrrolidines and γ-lactams is described. This reaction proceeds through the enantioselective AuI-catalyzed cyclization of allenenes to form a carbocationic intermediate that is trapped by an exogenous nucleophile, resulting in the highly diastereoselective construction of three contiguous stereogenic centers. A computational study (DFT) was also performed to gain some insight into the underlying mechanisms of these cycloadditions. The utility of this new methodology was demonstrated through the formal synthesis of (−)-isocynometrine.本文探究了亚磷酰胺配体（phosphoramidite ligands）在对映选择性一价金（AuI）催化中的应用价值，用于开发兼具高非对映选择性与对映选择性的一价金催化联烯烯烃（allenenes）环加成反应。本文报道了一种一价金催化合成3,4-二取代吡咯烷与γ-内酰胺的方法：该反应通过对映选择性一价金催化联烯烯烃环化生成碳正离子中间体，随后被外源性亲核试剂捕获，由此高非对映选择性地构建三个连续手性中心。此外，本文还开展了密度泛函理论（DFT）计算研究，以深入解析这类环加成反应的内在机理。通过(-)-异辛莫林的形式合成，验证了该新型合成方法的实用性。