雙膦配體結構對銠金屬催化不對稱串聯加成反應選擇性之影響研究

Abstract

本研究以掌性雙膦配體，控制銠金進行不對稱串聯加成反應。為提升目標產物2-茚酮的鏡像超越值（enantiomeric excess, ee），系統性探討了配體結構對反應結果的影響，包含二面角大小、配體官能基等因素。初步以(S)-BINAP與(S)-SEGPHOS為代表的剛性雙芳香環配體進行篩選，其中(S)-SEGPHOS展現最高選擇性，ee值達81%，其具有較小的二面角（67.2°）有利於形成穩定的掌性空間結構。進一步透過自合成的Tunaphos系列配體調控其二面角，觀察在相同官能基條件下由配體控制不同的二面角對反應立體選擇性的影響。結果顯示，具有碳鏈的配體隨著碳數增多，二面角由60°增至88°，對應ee值自51%提升至79%，與一般的diaryl 配體呈現相反的趨勢，證明除了二面角，diaryl旁的取代基對於選擇性也是有很大的影響力。此外，配體效應亦與受質電子性與位像密切相關，推電子基（如OMe，OEt，OBn）與大體積酯基受質可進一步穩定過渡態、提升催化效率與選擇性。綜合結果指出，配體設計中的二面角、結構以及取代基，皆為影響不對稱反應選擇性之關鍵因素。

In this study, chiral bisphosphine ligands were employed to control rhodium-catalyzed asymmetric tandem addition reactions. To improve the enantiomeric excess (ee) of the target product, 2-indanone, a systematic investigation was conducted on the influence of ligand structure, including dihedral angles and functional groups. Initial screening using rigid biaryl ligands such as (S)-BINAP and (S)-SEGPHOS showed that (S)-SEGPHOS delivered the highest enantioselectivity with an ee of 81%, attributed to its smaller dihedral angle (67.2°), which favors the formation of a well-defined chiral environment.Further exploration using a series of self-synthesized Tunaphos ligands enabled fine-tuning of the dihedral angle under constant functional group conditions. It was observed that increasing the carbon chain length in these ligands led to a gradual increase in dihedral angle (from 60° to 88°), accompanied by an improvement in ee (from 51% to 79%). This trend is opposite to that observed in traditional diaryl ligands, suggesting that substituents adjacent to the biaryl units also play a significant role in stereoselectivity. Additionally, the ligand effect was closely related to the electronic and steric properties of the substrates. Electron-donating groups (such as OMe, OEt, and OBn) and bulky ester substituents were found to stabilize the transition state, thereby enhancing both catalytic efficiency and selectivity.These results highlight that dihedral angle, ligand framework, and substituent effects are all critical factors influencing the stereoselectivity of asymmetric reactions.