Asymmetric carbon-carbon formation based on soft metal-hard anion conjugated catalysis

软金属-硬阴离子共轭不对称催化剂，如CuF和CuOR显示出独特的反应活性。与多功能碳亲核试剂如烯丙基硅烷、烯丙基硼酸酯、烯酮甲硅烷基缩醛、烯基硅烷、烯基硼酸酯、芳基硅烷和芳基硼酸酯结合，它们将硬阴离子快速转移到硬金属（Si和B）上。所得的Cu硅酸盐或硼酸盐可以将软碳亲核试剂转移回软Cu，产生高度亲核的Cu基亲核试剂，例如烯丙基铜、烯醇化铜、烯基铜和芳基铜。手性亲核试剂使用手性膦生成。铜基亲核试剂具有很高的反应活性，并对酮和酮亚胺实现了催化不对称加成反应。将软金属-硬阴离子共轭不对称催化的概念推广到丙二烯酯、酮和频哪醇硼酸酯的三组分反应。由Cu催化剂和频哪醇硼酸酯，通过金属转移生成氢化铜。氢化铜化学选择性地还原联烯酯，生成烯醇化铜。烯醇化铜对酮的加成反应具有对映选择性。重要的是，反应模式是可调的手性膦结构。以DTBM-SEGPHOS为配体，反应以γ-顺式选择性方式进行。而以谷硫磷为配体则选择性地生成α-加合物。这些结果表明，多组分反应的反应模式可以通过手性催化剂来控制。

Soft metal-hard anion conjugated asymmetric catalysts, such as CuF and CuOR display unique reactivity. Combined with versatile carbon nucleophiles, such as allylsilanes, allylboronates, ketene silyl acetals, alkenylsilanes, alkenylboronates, arylsilanes, and arylboronates, they quickly transfer hard anion onto hard metals (Si and B). Resulting Cu silicates or borates can transfer soft carbon nucleophiles back to soft Cu, generating highly nucleophilic Cu-based nucleophiles, such as allylcopper, copper enolates, alkenylcopper, and aiylcopper. Chiral nucleophiles are to be generated using chiral phosphines. The Cu-based nucleophiles are highly reactive, and catalytic asymmetric addition to ketones and ketoimines were realized. The concept of soft metal-hard anion conjugated asymmetric catalysis was extended to three-component reaction of an allenic ester, ketones, and pinacolboronate. From the Cu catalyst and pinacolboronate, copper hydride was generated through transmetalation. The copper hydride reduced allenic ester chemoselectively, and copper enolate was generated. The copper enolate added to ketones enantioselectively. Importantly, reaction pattern was tunable by the chiral phosphine structure. Using DTBM-SEGPHOS as a ligand, the reaction proceeded through γ-cis selective manner. Whereas, α-adduct was selectively produced using Taniaphos as a ligand. These results demonstrated that the reaction pattern of the multi-component reaction can be controlled by the chiral catalyst.