Bis-(N-heterocyclic carbene) Manganese-Catalyzed Direct α-Branched Methylation of Ketones Using Methanol

doi:10.6023/cjoc202603028

Abstract

The α-branched methylation of ketones employing methanol as a C1 source via a hydrogen-borrowing strategy represents an attractive yet challenging transformation. Herein, the efficient α-branched methylation of ketones with methanol catalyzed by a bis-N-heterocyclic carbene manganese(I) complex under phosphine-free conditions was reported. A broad range of aromatic propiophenone derivatives are well-tolerated, affording the corresponding branched α-methylated ketones in good yields. For acetophenone derivatives, selective double methylation is also feasible with good product yields. Mechanistic studies revealed that the α-methylation proceeds via a borrowing hydrogen pathway in our system.

Key words: borrowing hydrogen, manganese catalysis, methylation, methanol, N-heterocyclic carbene

Cite this article

Xiaobing Lan, Yanan Yu, Jun Chen, Zhenjie Yang, Ning Wang, Zhuofeng Ke. Bis-(N-heterocyclic carbene) Manganese-Catalyzed Direct α-Branched Methylation of Ketones Using Methanol[J]. Chinese Journal of Organic Chemistry, 2026, 46(7): 2751-2759.

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Entry	Base	Catalysis	Catalysis/mol/%	Solvent	Time/h	Yield^b/%
1^d	NaOH	[Mn]	5	Toluene	12	Trace
2^d	KO^tBu	[Mn]	5	Toluene	12	9
3	KO^tBu	[Mn]	5	Toluene/MeOH (V∶V=9∶1)	12	38
4	NaOH	[Mn]	5	Toluene/MeOH (V∶V=9∶1)	12	27
5	KO^tBu	[Mn]	5	MeOH	12	89
6	KO^tBu	[Mn]	2	MeOH	12	86
7	KO^tBu	[Mn]	1	MeOH	12	85
8	KOH	[Mn]	1	MeOH	12	90
9	NaOH	[Mn]	1	MeOH	12	86
10	K₂CO₃	[Mn]	1	MeOH	12	11
11^c	KO^tBu	[Mn]	1	MeOH	12	88
12^c	KOH	[Mn]	1	MeOH	12	43
13^c	NaOH	[Mn]	1	MeOH	12	40
14^e	KO^tBu	[Mn]	1	MeOH	12	38
15^f	KO^tBu	[Mn]	1	MeOH	12	Trace
16^g	KO^tBu	[Mn]	1	MeOH	12	Trace
17^h	KO^tBu	[Mn]	1	MeOH	12	Trace
18	KO^tBu	[Mn]	—	MeOH	12	0
19	—	[Mn]	1	MeOH	12	0
20	KO^tBu	MnBr(CO)₅	1	MeOH	12	0
21	KO^tBu	MnCl₂	1	MeOH	12	0
22	KO^tBu	Mn(acac)₃	1	MeOH	12	0
23	KO^tBu	[Mn]	1	MeOH/H₂O (V∶V=9∶1)	12	Trace
24	KO^tBu	[Mn]	1	MeOH/H₂O (V∶V=8∶2)	12	0

Entry	Base	Catalysis	Catalysis/mol/%	Solvent	Time/h	Yield^b/%
1^d	NaOH	[Mn]	5	Toluene	12	Trace
2^d	KO^tBu	[Mn]	5	Toluene	12	9
3	KO^tBu	[Mn]	5	Toluene/MeOH (V∶V=9∶1)	12	38
4	NaOH	[Mn]	5	Toluene/MeOH (V∶V=9∶1)	12	27
5	KO^tBu	[Mn]	5	MeOH	12	89
6	KO^tBu	[Mn]	2	MeOH	12	86
7	KO^tBu	[Mn]	1	MeOH	12	85
8	KOH	[Mn]	1	MeOH	12	90
9	NaOH	[Mn]	1	MeOH	12	86
10	K₂CO₃	[Mn]	1	MeOH	12	11
11^c	KO^tBu	[Mn]	1	MeOH	12	88
12^c	KOH	[Mn]	1	MeOH	12	43
13^c	NaOH	[Mn]	1	MeOH	12	40
14^e	KO^tBu	[Mn]	1	MeOH	12	38
15^f	KO^tBu	[Mn]	1	MeOH	12	Trace
16^g	KO^tBu	[Mn]	1	MeOH	12	Trace
17^h	KO^tBu	[Mn]	1	MeOH	12	Trace
18	KO^tBu	[Mn]	—	MeOH	12	0
19	—	[Mn]	1	MeOH	12	0
20	KO^tBu	MnBr(CO)₅	1	MeOH	12	0
21	KO^tBu	MnCl₂	1	MeOH	12	0
22	KO^tBu	Mn(acac)₃	1	MeOH	12	0
23	KO^tBu	[Mn]	1	MeOH/H₂O (V∶V=9∶1)	12	Trace
24	KO^tBu	[Mn]	1	MeOH/H₂O (V∶V=8∶2)	12	0

双齿N-杂环卡宾锰催化酮与甲醇的直接α-支链甲基化反应