Mn(0) Catalyzed the Asymmetric Hydrogenation of Ketones

doi:10.6023/A25030092

Abstract

The field of manganese-catalyzed asymmetric hydrogenation of ketones has witnessed significant advancements since 2017. However, the catalysts employed have predominantly been monovalent manganese catalysts based on Mn(CO)₅Br. In contrast, there have been few reports on the use of more economically viable zero-valent manganese catalysts derived from Mn₂(CO)₁₀. In light of this, a novel class of tetradentate PNNN ligands was designed and synthesized, which were subsequently applied to the Mn(0) catalyzed asymmetric hydrogenation of simple ketones. Mn₂(CO)₁₀ was employed for the first time as a metal precursor in the manganese-catalyzed asymmetric hydrogenation of ketones, offering a new Mn(0) catalytic system for the synthesis of chiral alcohols and their intermediates. After a systematic optimization of reaction conditions which focused on ligand, solvent, base, and additive parameters, the optimal reaction conditions were determined as follows: the chiral catalyst (n_S/n_C=100/1) was formed in situ by combining of ligand 6d and Mn₂(CO)₁₀ in ethanol at room temperature, the reaction proceeded under a hydrogen pressure of 3.5 MPa at a temperature of 35 ℃, with ethanol as the solvent, KO^tBu as the base, and hexafluoroisopropanol (HFIP) as an additive, over a period of 24 h. Under mild conditions, a substrate scope investigation was conducted using 25 different ketones as substrates to evaluate the generality of this catalytic system. The results demonstrated that the target chiral alcohols were obtained with great yields (90%~96% yields), along with high enantioselectivities (up to 90% ee). This catalytic system exhibited excellent substrate generality, highlighting its broad applicability for the asymmetric transformation of diverse ketones. This research achievement presents the first example of a Mn(0)-based catalytic system for manganese catalyzed asymmetric hydrogenation, it is anticipated that this work will inspire chemists to develop more economical and environmentally friendly catalytic systems, give rise to the research on the mechanism of Mn(0)-catalyzed asymmetric hydrogenation, thereby advancing the field of sustainable asymmetric synthesis.

Key words: Mn₂(CO)₁₀, novel ligand, asymmetric hydrogenation, chiral alcohols

Cite this article

Bin Li, Jingfeng Zhang, Huifang Nie, Zexing Lu, Guidong Yang, Shengyong Zhang. Mn(0) Catalyzed the Asymmetric Hydrogenation of Ketones[J]. Acta Chimica Sinica, 2025, 83(7): 661-666.

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Entry	配体	金属前体	转化率^a/%	对映选择性ee^b/%
1	6a	[Ir(COD)Cl]₂	99	37
2	6g	[Ir(COD)Cl]₂	65	14
3	6a	Mn(CO)₅Br	99	69
4	6a	Mn₂(CO)₁₀	99	67
5	6b	Mn₂(CO)₁₀	99	59
6	6c	Mn₂(CO)₁₀	—	—
7	6d	Mn₂(CO)₁₀	99	77
8	6e	Mn₂(CO)₁₀	47	79
9	6f	Mn₂(CO)₁₀	99	67
10	6g	Mn₂(CO)₁₀	99	56

Entry	配体	金属前体	转化率^a/%	对映选择性ee^b/%
1	6a	[Ir(COD)Cl]₂	99	37
2	6g	[Ir(COD)Cl]₂	65	14
3	6a	Mn(CO)₅Br	99	69
4	6a	Mn₂(CO)₁₀	99	67
5	6b	Mn₂(CO)₁₀	99	59
6	6c	Mn₂(CO)₁₀	—	—
7	6d	Mn₂(CO)₁₀	99	77
8	6e	Mn₂(CO)₁₀	47	79
9	6f	Mn₂(CO)₁₀	99	67
10	6g	Mn₂(CO)₁₀	99	56

Entry	溶剂	碱	转化率^a/%	对映选择性ee^b/%
1	MeOH	KO^tBu	99	75
2	ⁱPrOH	KO^tBu	58	70
3	EtOH	KO^tBu	99	77
4	TFE	KO^tBu	18	68
5	THF	KO^tBu	NR	—
6	HFIP	KO^tBu	NR	—
7	MTBE	KO^tBu	NR	—
8	EtOH	NaO^tBu	99	76
9	EtOH	LiO^tBu	99	78
10	EtOH	Na₂CO₃	58	83
11	EtOH	K₂CO₃	62	81
12	EtOH	Cs₂CO₃	95	77
13	EtOH	NaOMe	98	77
14	EtOH	LiOMe	78	78
15	EtOH	NaOH	98	78
16	EtOH	KOH	99	78
17^c	EtOH	KO^tBu	99	78
18^d	EtOH	KO^tBu	99	84

Entry	溶剂	碱	转化率^a/%	对映选择性ee^b/%
1	MeOH	KO^tBu	99	75
2	ⁱPrOH	KO^tBu	58	70
3	EtOH	KO^tBu	99	77
4	TFE	KO^tBu	18	68
5	THF	KO^tBu	NR	—
6	HFIP	KO^tBu	NR	—
7	MTBE	KO^tBu	NR	—
8	EtOH	NaO^tBu	99	76
9	EtOH	LiO^tBu	99	78
10	EtOH	Na₂CO₃	58	83
11	EtOH	K₂CO₃	62	81
12	EtOH	Cs₂CO₃	95	77
13	EtOH	NaOMe	98	77
14	EtOH	LiOMe	78	78
15	EtOH	NaOH	98	78
16	EtOH	KOH	99	78
17^c	EtOH	KO^tBu	99	78
18^d	EtOH	KO^tBu	99	84

Mn(0)催化酮的不对称氢化反应