Wang Qingmin, Professor of Nankai University, research group: visible light induced Giese reaction of non activated iodoalkanes catalyzed by manganese

It has been a key step in drug synthesis to construct carbon carbon bonds by simple methods In recent years, organic synthesis chemists have been developing more effective reactions for the formation of carbon carbon bonds Among them, the addition of alkyl radicals to electron deficient alkenes, i.e Giese reaction, provides a very effective way to construct a new SP 3 carbon carbon bond Traditional Giese reactions often require the use of organotin reagents, resulting in poor functional compatibility and chemical selectivity In recent years, visible light catalyzed Giese reactions have been developed, but expensive metal photocatalysts (iridium and ruthenium) are often needed, and the range of substrates is still limited Therefore, it is of great significance to develop a wider range of applications and avoid the use of noble metal photocatalysts for Giese reaction Recently, the research group of Professor Wang Qingmin of Nankai University has made a breakthrough in this field Under the condition of light excitation, the Giese reaction of non activated iodoalkanes catalyzed by cheap and easily available Mn 2 (CO) 10 under visible light excitation has been realized through the strategy of capturing iodine atoms by manganese free radicals Relevant research results were published in Chem Commun (chem Commun 2019, 55, 11707) Frontier research achievements: the Giese reaction of non activated iodoalkanes catalyzed by manganese under the excitation of visible light Professor Wang Qingmin's research group of Nankai University has done a series of pioneering work in the field of photocatalysis free radical coupling reaction (SCI Adv 2019, 5, eaax9955; chem SCI 2019, 10, 976; org Lett 2019, 21, 5728; org Lett 2018, 20, 5661; Org Lett 2016, 18, 4686), and published a review (chem EUR J 2019, 25, 2949) Because alcohols and alkyl iodides are widely available and easily obtained, and alcohols can be converted into alkyl iodides in one step, the author hopes to develop Giese reaction with cheap and easily available metal as photocatalyst and alkyl iodides as free radical source under visible light catalysis The challenge of this reaction is that the reduction potential of alkyl iodide is low, and it is difficult to get alkyl radicals from common photocatalysts In recent years, Mn 2 (CO) 10 as a new photocatalyst can obtain [ Mn (CO) 5] under the excitation of visible light, and [ Mn (CO) 5] can grab the iodine atom of alkyl iodine to obtain alkyl radicals and Mn (CO) 5I However, this process is different from other photocatalysts' single electron redox process, and the iodine atom grabbing process will not be affected by the redox potential of the substrate Based on this property, the author has realized the Giese reaction of the addition of nonactivated iodoalkanes to electron deficient alkenes catalyzed by Mn 2 (CO) 10, which is cheap and easy to obtain under the excitation of visible light (Fig 1) The reaction conditions are mild and can be carried out under sunlight, with good functional group compatibility and substrate application range More importantly, the reaction happened selectively on the SP 3 C-I bond For the SP 2 C-I bond, C-Cl bond and C-Br bond, the reaction could not happen Fig 1 visible light promoted Giese reaction (source: chem Commun.) the author optimized the reaction conditions with benzyl acrylate (1) as Michael receptor and iodo cyclohexane (2) as alkyl radical precursor When Mn 2 (CO) 10 is used as photocatalyst, 2,6-dimethyl-1,4-dihydro-3,5-pyridyldicarboxylic acid diethyl ester (he) is used as reducing agent and dimethyl sulfoxide is used as solvent, the target product is obtained in 96% yield (Table 1) Table 1 screening of reaction conditions a (source: chem Commin.) after obtaining the optimal conditions, the author first inspected the application scope of alkyl iodine substrate (Table 2) The reaction has a wide range of application for alkyl iodine and good functional group compatibility For the first-order alkyl iodide, the product (4-17) can be obtained in medium to good yield The reaction is compatible with chlorine, iodine, trifluoromethyl, ester group, silicon group and other functional groups, and the product with medium yield (8 - 13) is obtained It is worth noting that for the 4-iodobenzylethyl iodide substrate, the reaction takes place selectively on the SP 3 C-I bond, and the reaction can also be carried out under sunlight, and the yield is almost no loss (17) For the second-order alkyl iodides, the yield of the product is higher than that of the first-order iodoalkanes (18-24), because the second-order alkyl radicals are more stable and nucleophilic The reaction can also be used for tertiary alkyl iodine, and the product (25, 26) can be obtained in a better yield Table 2 application range of alkyl iodine a (source: chem Commun.) then the author inspected the application range of electron deficient olefin substrate (Table 3) This reaction also has a good range of application and functional compatibility for Michael receptor Specifically, the acrylate containing various substituents can get the target product (27 - 35) in good yield The reaction can also be applied to imine maleate (36, 37), acrylamide (38 - 40) and vinyl sulfone (41) substrates For electron deficient alkenes, the reaction is compatible with ester, amide, hydroxyl, sulfone and other functional groups Table 3 scope of application of Michael receptor A (source: chem Commun.) although most of the alkyl iodides are easy to obtain, they are more expensive for some complex alkyl iodides, so the use of one-step conversion of alkyl alcohol to alkyl iodides can make the reaction substrate range wider, which makes the method more practical Using natural menthol and sterol to convert to alkyl iodine in one step, the author was able to obtain the product of Giese reaction in medium yield (Fig 2a) In order to further verify the practicability of the reaction, the author realized the gram level preparation of the reaction under the sunlight, and obtained the Suzuki coupling product in a medium to good yield from 17 (Fig 2b) Fig 2 Application of reaction (source: chem Commun.) after exploring the application scope of reaction substrate and the application of reaction, the author studied the reaction mechanism (Fig 3) When 2.5 equivalent free radical trapping group (tempo) was added, the reaction was completely inhibited, and the product of cyclohexane radical trapping by tempo was detected in high-resolution mass spectrometry When 2.5 equivalent free radicals were added to capture 1,2-stilbene, the reaction was completely inhibited In order to further verify the mechanism of the reaction, the free radical clock experiment was carried out When iodomethylcyclopropane was used as the reaction substrate, the double substituted cyclopentane product (51) could be obtained in 36% yield When 5-hexene-1-iodine was used as the reaction substrate, the product of cyclization and addition was obtained in 57% yield (53) These experiments show that the reaction undergoes the course of free radicals In order to verify the origin of the hydrogen atom in the product, the deuterium experiment was carried out When using deuterium dimethyl Maple as the reaction solvent, no deuterium product was obtained When using deuterium instead of he as reductant, the deuterium product in the product is completely obtained, which shows that the deuterium atom in the product comes from he Figure 3 mechanism experiment (source: chem Commun.) based on mechanism experiment and related literature reports, the author proposed the following reaction mechanism (Figure 4) Mn 2 (CO) 10 photocatalyst can obtain [ Mn (CO) 5] under the excitation of visible light, [ Mn (CO) 5] can grab the iodine of alkyl iodine to obtain alkyl radical a and Mn (CO) 5I, alkyl radical a can add intermediate B to Michael receptor, intermediate B can grab Hydrogen atom of he to obtain final product and dihydropyridine radical, dihydropyridine can reduce Mn (CO) 5I to obtain [ Mn (CO) 5] The reaction mechanism proposed in Fig 4 (source: chem Commin.) Summary: Professor Wang Qingmin's research team reported a Giese reaction of Michael's receptor addition to nonactivated iodoalkanes catalyzed by cheap and easily available Mn 2 (CO) 10 under visible light excitation The reaction conditions are mild, and it can also react in sunlight, and it has good functional compatibility and substrate application range More importantly, the reaction happened selectively on the SP 3 C-I bond For the SP 2 C-I bond, C-Cl bond and C-Br bond, the reaction could not happen The corresponding author of this work is Professor Wang Qingmin from Nankai University Dong Jianyang, a doctoral candidate of Nankai University, is the first author of the paper Liu Yuxiu, a deputy researcher of Nankai University, song Hongjian, a lecturer, Wang Jianchen, a postgraduate student and Wang Zhen have also made great contributions to the smooth progress of the work The above research work was supported by the national key R & D plan (2018yfd02010, 2010), the National Natural Science Foundation (2173200221672117), and the doctoral research innovation program of the school of chemistry, Nankai University Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information website, chembeangoapp, chembeango official micro blog, CBG information wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the representative research groups in China, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.