蒽光二聚体衍生的手性单膦配体: 借助化学拆分的制备路线和不对称烯丙基胺化的合成应用

doi:10.6023/cjoc202409013

摘要/Abstract

蒽光二聚体具有前手性骨架, 因此可作为构筑新型手性配体的核心结构. 此前工作中具备光学活性的蒽光二聚体衍生的单膦配体均由高效液相色谱拆分得到, 成为制约合成规模与成本控制的瓶颈. 此研究发展了一种基于化学拆分、廉价且易于操作的配体合成新路线. 该路线的特点是利用脯氨酸衍生的手性辅基, 成功实现了对1-氨基取代的蒽光二聚体的化学拆分, 进而利用拆分后的光学纯对映异构体, 针对一系列蒽光二聚体衍生的单膦配体进行发散式地合成. 经过上述化学拆分路线合成的手性单膦配体(S_a,S_p)-L1被应用于钯催化的不对称烯丙基胺化反应, 适用于多种不同取代的芳胺类亲核试剂, 并且具有高产率和对映选择性.

关键词: 蒽光二聚体, 手性单膦配体, 化学拆分, 烯丙基胺化, 钯催化

Anthracene photodimer has a prochiral skeleton, which can be employed as the core structure to construct new chiral ligands. In previous works, the monophosphine ligands derived from optically active anthracene photodimer were prepared through resolution using high performance liquid chromatography, which became a bottleneck for the synthetic scale and cost control. Herein, an inexpensive and operationally friendly route for these ligands is reported, based on chemical resolution. The route features the use of a proline-derived chiral auxiliary that facilitate successful chemical resolution of 1-amino substituted anthracene photodimer. From the resulting optically pure enantiomers, divergent syntheses of a series of anthracene photodimer-derived monophosphine ligands have been achieved. Prepared from the above route, the chiral monophosphine ligand (S_a,S_p)-L1 has been applied to palladium-catalyzed asymmetric allylic amination reactions, which is suitable for a wide range of aniline-type nucleophiles with high yield and enantioselectivity.

Key words: anthracene photodimer, chiral monophosphine ligand, chemical resolution, asymmetric allylic amination, palladium catalysis

引用此文

任天磊, 汪鑫, 丛欢. 蒽光二聚体衍生的手性单膦配体: 借助化学拆分的制备路线和不对称烯丙基胺化的合成应用[J]. 有机化学, 2025, 45(6): 2208-2221.

Tianlei Ren, Xin Wang, Huan Cong. Anthracene Photodimer-Derived Chiral Monophosphine Ligands: Preparative Route through Chemical Resolution and Synthetic Application in Asymmetric Allylic Amination[J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2208-2221.

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图/表 6

图式1. (a)通过化学拆分制备蒽光二聚体衍生的对映体富集的单膦配体和(b)单膦配体在钯催化不对称烯丙基胺化反应中的应用

Scheme 1. (a) Preparation of enantioenriched monophosphine ligands derived from anthracene photodimer through chemical resolution; (b) Application of the monophosphine ligand in palladium-catalyzed asymmetric allylic amination reaction

图式2. 1-氨基取代的蒽光二聚体的化学拆分

Scheme 2. Chemical resolution of 1-amino-substituted anthracene photodimer

图1. HPLC法测定拆分后(Sp,S)-4和(Rp,S)-4的de值

Figure 1. de values of (Sp,S)-4 and (Rp,S)-4 after resolution determined by HPLC method HPLC condition: OD-H column, n-hexane/i-PrOH (V/V=97/3) as the mobile phase, flow rate=1.0 mL/min.

图式3. 发散性合成蒽光二聚体衍生的手性单膦配体

Scheme 3. Divergent synthesis of chiral monophosphine ligands derived from anthracene photodimer

表1. 手性配体的评估a

Table 1. Evaluation of the chiral ligands

表2. 底物范围a

Table 2. Substrate scope

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