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CuO，表现出独特的反应活性。与多种碳亲核试剂，如烯丙基硅烷、烯丙基硼酸酯、烯基硅烷缩醛、烯基硅烷、烯基硼酸盐、芳基硅烷和芳基硼酸盐相结合，它们能迅速将硬阴离子转移到硬金属(硅和硼)上。生成的铜硅酸盐或硼酸盐可以将软碳亲核剂转移回软铜，生成高度亲核的铜基亲核剂，如烯丙基铜、铜烯醇酸盐、烯基铜和丙烯基铜。用手性膦生成手性亲核试剂。铜基亲核试剂具有很高的活性，实现了酮和酮亚胺的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扩展到烯丙酸酯、酮和频碳硼酸酯的三组分反应。以铜为催化剂，与频碳硼酸盐反应生成氢化铜。氢化铜在化学上选择性地还原了烯丙基酯，生成了烯醇铜。铜烯醇盐对映体选择性地加入到酮中。重要的是，反应模式可以通过手性膦结构进行调节。反应以DTBM-SEGPHOS为配体，以γ-cis选择性方式进行。而α-加合物是以磷酸二氢钾为配体选择性合成的。这些结果表明，手性催化剂可以控制多组分反应的反应模式。

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.