基于氟仿衍生的三氟甲基硼络合物参与的烯烃氢三氟甲基化反应

doi:10.6023/A23040127

摘要/Abstract

含三氟甲基基团的有机化合物在医药、农药和材料等领域有着广泛的用途. 氟仿是最廉价、原子经济性最高的三氟甲基源, 但呈化学惰性. 本工作以氟仿衍生的三氟甲基硼络合物为三氟甲基化试剂, 在可见光催化条件下实现了苯乙烯、丙烯酸酯和丙烯酰胺类烯烃的氢三氟甲基化反应. 该反应效率高, 区域选择性专一, 在得到氢三氟甲基化产物的同时, 生成的硼酸频那醇酯可回收利用.

关键词: 三氟甲基化, 氟仿, 三氟甲基硼络合物, 可见光催化, 氢三氟甲基化

Trifluoromethyl-containing organic compounds have found widespread applications in various areas such as pharmaceuticals, agrochemicals and materials science. Fluoroform is the cheapest and most atom-economical trifluoromethyl source, but chemically inert. The use of fluoroform in trifluoromethylation reactions remains a formidable challenge. In this work, with a trifluoromethylboron complex derived from fluoroform as the trifluoromethylating reagent, the hydrotrifluoromethylation of styrenes, acrylates and acrylamides is successfully accomplished under photoredox catalytic conditions. Thus, with potassium bis(trimethylsilyl)amide (KHMDS) as the base, the reaction of fluoroform with (4-methoxyphenyl)boronic acid pinacol ester at room temperature (r.t.) leads to the corresponding trifluoromethylboron complex in 59% yield as a white solid stable in air and moisture. With the ate complex as the trifluoromethylating reagent, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6- dicyanobenzene (4CzIPN) as the photocatalyst and benzoic acid as the proton source, the reaction of styrenes in N,N-dimethylacetamide (DMA) at r.t. under blue light irradiation provided the corresponding anti-Markovnikov hydrotrifluoromethylation products in satisfactory yields. The protocol is also applicable to various acrylates as well as acrylamides, furnishing the expected ꞵ-trifluoromethylated esters or amides. A wide functional group compatibility is observed. The reaction is efficient and highly regioselective. In addition, the pinacol boronate generated along with the hydrotrifluoromethylation products can be recovered and reused. A redox-neutral mechanism is proposed, which involves the oxidative generation of CF₃ radicals, addition to C=C bonds, subsequent single electron reduction and protonation.

Key words: trifluoromethylation, fluoroform, trifluoromethylboron complex, photocatalysis, hydrotrifluoromethylation

引用此文

李飞, 丁汇丽, 李超忠. 基于氟仿衍生的三氟甲基硼络合物参与的烯烃氢三氟甲基化反应[J]. 化学学报, 2023, 81(6): 577-581.

Fei Li, Huili Ding, Chaozhong Li. Hydrotrifluoromethylation of Alkenes with a Fluoroform-Derived Trifluoromethylboron Complex[J]. Acta Chimica Sinica, 2023, 81(6): 577-581.

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图/表 7

图1. 基于氟仿的烯烃氢三氟甲基化反应

Figure 1. Hydrotrifluoromethylation of alkenes with reagents derived from fluoroform

图2. 氟仿制备三氟甲基硼络合物2

Figure 2. Preparation of trifluoromethylboron complexes 2 from fluoroform

Entry^a	Variations from the “standard conditions”	Yield^b/%
1	none	75 (72)
2	less amount (2 mol%) of 4CzIPN used	51
3	4DPAIPN in place of 4CzIPN	21
4	AcOH in place of PhCOOH	69 (65)
5	^tBuOH in place of PhCOOH	26
6	H₂O in place of PhCOOH	36
7	DCM in place of DMA	6
8	PhCl in place of DMA	5
9	MeCN in place of DMA	60
10	without PhCOOH	8
11	without blue LEDs	0
12	without 4CzIPN	0

表1. 反应条件的优化

Table 1. Optimization of reaction conditions

表2. 苯乙烯底物适用范围a

Table 2. Substrate scope of styrenes a

表3. 丙烯酸酯和丙烯酰胺底物适用范围a

Table 3. Substrate scope of acrylates and acrylamidesa

图3. 克级反应和回收实验

Figure 3. Gram-scale reaction and recovery experiment

图4. 自由基钟实验和提出的机理

Figure 4. Radical clock experiment and the proposed mechanism

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