Ir-catalyzed allylation of enolates and nitroalkanes

描述（由申请人提供）： 随着FDA对单一对映体制剂的重视程度的增加，需要从简单的非手性输入合成复杂的纯手性化合物的新方法。钯催化的不对称烯丙基烷基化反应（AAA）主要是生成不对称烯丙基碳酸酯的线型产物，已被用于合成许多天然产物。相比之下，Ir催化的反应以高产率产生支化产物。目前，Ir催化的烯丙基取代化学仅限于醇、胺和稳定的烯醇化亲核试剂。此外，在这些反应中如何实现高对映体和非对映体控制的机制是未知的。 各种新的Ir-亚磷酰胺配合物将扩大范围，这种化学不稳定的烯醇化物（酮，酯，酰胺）和硝基烷烃进行调查。在除了最简单的情况之外的所有情况下，产物将含有两个新的、邻接的立体中心，并且难以通过目前已知的方法以对映体纯的形式合成。Ir-催化烯丙基取代的机制也将通过相关Ir-烯丙基络合物的合成、分离和表征来研究。

DESCRIPTION (provided by applicant): With the increasing importance placed on single-enantiomer formulations by the FDA, new methods for the synthesis of complex, homochiral compounds from simple, achiral inputs are required. Pd-catalyzed asymmetric allylic alkylation (AAA), which has been used to synthesize a host of natural products, predominantly produces a linear product with unsymmetrical allylic carbonates. In contrast, the Ir-catalyzed reaction yields branched products in high yield. Presently, the Ir-catalyzed allylic substitution chemistry is limited to alcohol, amine, and stabilized enolate nucleophiles. In addition, the mechanism of how the high enantio- and diastereo-control is achieved in these reactions is unknown. A variety of new Ir-phosphoramidite complexes will be investigated for expanding the scope of this chemistry to unstabilized enolates (ketones, esters, and amides) and nitroalkanes. In all but the simplest cases, the products will contain two new, contiguous stereocenters and are difficult to synthesize in enantiopure form by currently known methods. The mechanism of the Ir-catalyzed allylic substitution will also be investigated by the synthesis, isolation, and characterization of relevant Ir-allyl complexes.