Asymmetric functionalization of the C(sp³)–H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with minimal manipulation of functional groups. Here, we report an asymmetric C(sp³)–H/C(sp³)–H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C–H bond, effectively complementing established methodology for allylic C–H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.

中文翻译：

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N-烯丙胺和 α-芳基酮的钯催化对映选择性 C(sp3)–H/C(sp3)–H Umpolung 偶联

C(sp ³ )-H 键的不对称功能化是一种有吸引力但具有挑战性的策略，可以实现多种成键事件，从而能够在对官能团进行最少操作的情况下精确组装分子复杂性。在这里，我们报告了N的不对称 C(sp ³ )–H/C(sp ³ )–H umpolung 耦合-烯丙胺和配位α-芳基羰基通过手性亚磷酰胺-钯催化。多种 α-杂芳基酮和 2-酰基咪唑具有良好的耐受性，为高效合成对映富集的 β-氨基-γ,δ-不饱和羰基衍生物开辟了一条方便且可调的途径，具有高水平的区域和立体选择性，能够提供非对称合成 Focalin 的关键中间体。该协议展示了N的 umpolung 反应性-烯丙基亚胺通过协同的质子和双电子转移过程来裂解烯丙基 C-H 键，有效地补充了已建立的烯丙基 C-H 官能化方法。计算研究和实验事实表明，α-杂芳基羰基和 2-酰基咪唑攻击 π-烯丙基钯物种的内球烯丙基化途径，其中与钯中心的氮配位使支链区域选择性的偏好成为可能。