Abstract：
To facilitate the discovery and development of new pharmaceuticals, the demand for novel stereofunctionalised building blocks has never been greater. Whilst molecules bearing quaternary and tetrasubstituted stereogenic centres are ideally suited to explore untapped areas of chemical space, the asymmetric construction ofsterically congested carbon centres remains a longstanding challenge in organic synthesis. The enantioselective assembly of acyclic stereogenic centres is even more demanding due to the need to restrict a much wider range of geometries and conformations of the intermediates involved. In this context, the catalytic asymmetric allylicalkylation (AAA) of acyclic prochiral nucleophiles, namely enolates, has become an indispensable tool to access a range of linearα-quaternary andα-tetrasubstituted carbonyl compounds. However, unlike the AAA of cyclic enolates with a fixed enolate geometry, to achieve high levels of stereocontrol in the AAA of acyclic enolates, the stereoselectivity of enolisation must be considered. The aim of this review is to offer acomprehensivediscussion of catalytic AAA reactions of acyclic prochiral enolates and their analogues to generate congested quaternary and tetrasubstituted chiral centres using metal, non-metal and dual catalysis, with particular focus given to the control of enolate geometry and its impact on the stereochemical outcome of the reaction.
摘要：
为促进新药的发现和开发,对新型立体功能化构件的需求从未如此之大。虽然具有四元和四取代立体中心的分子非常适合探索化学空间的未开发区域，空间拥挤的碳中心的不对称结构仍然是有机合成的长期挑战。由于需要限制所涉及的中间体的更宽范围的几何形状和构象,无环立体中心的对映选择性组装甚至要求更高。在这种情况下，非环前手性亲核试剂的催化不对称烯丙基烷基化（AAA），即烯醇盐，已成为获得一系列线性α-季铵和α-四取代羰基化合物的必不可少的工具。然而,与具有固定烯醇化物几何形状的环状烯醇化物的AAA不同，为了在无环烯醇酯的AAA中实现高水平的立体控制，必须考虑烯醇化的立体选择性。这篇综述的目的是全面讨论无环前手性烯醇酯及其类似物的催化AAA反应，以使用金属产生拥挤的四元和四取代手性中心，非金属和双重催化，特别关注烯醇化物几何形状的控制及其对反应立体化学结果的影响。
