新型手性三齿PNN配体锰配合物催化的芳香酮类化合物的不对称氢化反应研究

doi:10.6023/A24040120

摘要/Abstract

非贵金属相较于贵金属具有廉价、低毒的特点, 因此发展用于酮的不对称催化氢化的高效、低毒的非贵金属催化剂在近些年受到广泛关注, 其中手性三齿PNN和PNP配体的锰配合物在多种酮的催化不对称氢化中表现出优异的性能, 但就底物类型和催化效率而言仍有待进一步提升. 基于此, 本工作将廉价易得的8-氨基喹啉骨架引入面手性二茂铁中合成了一系列含芳胺NH的三齿PNN配体L1~L4, 并将其Mn配合物成功用于简单芳基酮、苯并环烷酮、α-氨基酮等的催化不对称氢化(达到98% ee, 1000 TON). 反应使用K₂CO₃作碱, EtOH作溶剂, 对(S)-phenylephrine的重要中间体β-氨基醇2-49进行克级规模制备, 证明了该催化体系具有潜在的工业应用性. 对配合物Mn-L的高分辨质谱和红外光谱的初步表征和分析, 暗示其结构中含两个CO.

关键词: 芳胺NH, 手性PNN配体, 锰配合物, 催化不对称氢化, 手性醇

Since the first-raw metals have higher metal contamination limitations in pharmaceutical compounds and cheaper. Extensive global efforts have been devoted to the development of chiral catalysts with earth abundant, inexpensive, and nontoxic transitions metals. Nevertheless, non-precious metal catalysts in ketone hydrogenation are still far from satisfactory in terms of activity, selectivity and substrate scope. Recently, much effort has been devoted to the development of powerful chiral ligands for manganese-catalyzed enantioselective ketone hydrogenation. Based on this, in this work, we synthesized a series of three-toothed PNN ligands L1~L4 by introducing 8-aminoquinoline skeleton into facial chiral ferrocene, and applied these ligands to Mn-catalyzed asymmetric hydrogenation of a broad spectrum of ketones (49 examples) with high activities (1000 TON) and high enantioselectivities (up to 98% ee) using K₂CO₃ and EtOH as an industrially desirable base and solvent. To further demonstrate the utility of the developed Mn catalytic system, we applied it to the catalytic asymmetric hydrogenation of α-aminoketones (1-49, 1.46 g) with gram-scale and successfully obtained β-aminoalcohols (S)-2-49 in 1.25 g, 97% isolated yield and 81% ee within 24 h at 50 ℃ under hydrogen pressure of 4 MPa. Notably, the product (S)-2-49 is a key intermediate of (S)-phenylephrine. Although our attempts to get the crystal structure of Mn-L1 failed, the data of high resolution mass spectra and infrared spectra analysis strongly supported the hypothesized structure of Mn-L1, which contains two CO molecules.

Key words: arylamine NH, chiral PNN ligand, manganese complex, catalytic asymmetric hydrogenation, chiral alcohols

引用此文

江杏杏, 武卫龙, 任慧莹, 张凤, 莫文枝, 卢志强. 新型手性三齿PNN配体锰配合物催化的芳香酮类化合物的不对称氢化反应研究[J]. 化学学报, 2024, 82(7): 736-741.

Xingxing Jiang, Weilong Wu, Huiying Ren, Feng Zhang, Wenzhi Mo, Zhiqiang Lu. Novel Chiral Tridentate PNN Ligand Manganese Complex for Enantioselective Hydrogenation of Aromatic Ketones[J]. Acta Chimica Sinica, 2024, 82(7): 736-741.

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图/表 7

图1. 代表性的不对称氢化酮的手性PNN和PNP配体的锰配合物

Figure 1. Representative manganese complexes of chiral PNN and PNP ligands for asymmetric hydrogenation of ketones

图2. 含芳胺NH的手性三齿PNN配体L的合成路线

Figure 2. Synthesis route of chiral tridentate PNN ligand L containing arylamine NH

Entry	Ligand	Conv.^b/%	ee^c/%
1	L1	>99(98)	76
2	L2	>99(99)	77
3	L3	>99(57)	73
4	L4	>99(35)	74

表1. 配体的筛选a

Table 1. Screening liganda

Entry	Solvent	Base	Conv.^b/%	ee^c/%
1	MeOH	^tBuOK	81	75
2	EtOH	^tBuOK	>99	76
3	ⁱPrOH	^tBuOK	>99	63
4	THF	^tBuOK	>99	25
5	DCM	^tBuOK	>99	22
6	CH₃CN	^tBuOK	71	12
7	PhMe	^tBuOK	>99	10
8	MTBE	^tBuOK	>99	11
9	HFIPA	^tBuOK	trace	ND
10	EtOH	K₂CO₃	>99	78
11	EtOH	Cs₂CO₃	95	76
12	EtOH	MeONa	94	77
13	EtOH	EtONa	94	76
14	EtOH	^tBuONa	>99	76
15	EtOH	MeOK	98	76
16	EtOH	KOH	97	74
17	EtOH	NaOH	93	70
18^d	EtOH	K₂CO₃	>99	78

表2. 反应条件优化a

Table 2. Condition optimizationa

表3. 底物普适性研究a

Table 3. Substrate scopea

图3. (S)-phenylephrine的克级规模制备

Figure 3. Gram-scale preparation of (S)-phenylephrine

图4. 可能的反应机理

Figure 4. Proposed reaction mechanism

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