Green chem.: a visible light mediated D-A and azad-a reaction was realized with ketone as catalyst by shoubhik Das group, University of Gottingen, Germany

Diels alder (D-A) reaction is a basic strategy for the construction of cyclohexene derivatives with new stereocenters It has been widely used in organic synthesis, pharmaceutical industry and biochemistry In order to improve the conversion and stereoselectivity of D-A reaction, Evans and Macmillan developed different strategies However, the electrical mismatching coupling between diene and amphiphilic diene is challenging and demanding The Ru and Cr complexes developed by Yoon, shores and Ferreira showed excellent reactivity to the electrophilic amphiphiles under visible light, but the metal free photocatalysts did not show reactivity (photo source: Green Chemistry) azadiels alder reaction is also a direct and effective method for the synthesis of azacyclic compounds At present, it has been reported that visible light reacts with Ru and Cr catalyzed azadiels alder However, all visible light mediated D-A or azad-a reactions require transition metal based photocatalysts Recently, the shoubhik Das group of the University of Gottingen in Germany has realized the visible light mediated Diels alder and azadiels alder reactions using simple ketones as catalysts The results were published on the recent green chemistry (DOI: 10.1039 / c9gc00485h) Firstly, trans anethole (1a) and 2,3-dimethyl-1,3-butadiene (1b) were used as diene to optimize the Diels alder reaction The optimum reaction conditions were determined as follows: 12 W blue LED as light source, nitromethane as solvent, MgSO 4 as desiccant and fluorenone as catalyst After determining the optimal reaction conditions, the author extended this non-metallic catalytic system to other electric rich amphiphiles and dienes (scheme 1) The [4 + 2] cycloaddition of diene 2,3-dimethyl-1,3-butadiene and other electrophilic dienes such as laurene and isoprene can be carried out successfully In addition, 1,2-dimethoxy-4-propenylbenzene and 2,5-furandione are also suitable for this system, and 9-vinylcarbazole can also act as amphiphilic Inspired by the role of fluorenone in the [4 + 2] cycloaddition reaction, the authors try to apply these reaction conditions to the azad-a reaction to directly synthesize important N-heterocycles The synthesis of 2,3-dihydropyridine-4 (1H) - one derivatives usually requires a noble metal catalyst and a long reaction time; the amphiphilic (E) - 1 - (4-methoxyphenyl) - n-phenylmethylimine (1AA) and danishefsky diene (1ab) need only 2 hours to convert to 1Ac in an excellent yield under the catalysis of fluorenone In addition, we also studied the reaction of diene and amphiphilic diene in different proportion, and found that when the ratio of diene and amphiphilic diene is 2:1, the required product can be obtained in 96% yield Under the optimized reaction conditions, the fluorenone catalyst was applied to other imines to synthesize a variety of 2,3-dihydropyridine-4 (1H) - one derivatives (scheme 2) All kinds of electric rich imines show high reactivity, and the yield is as high as 96% This shows that the catalyst has good tolerance to alkyl, aryl and heteroaryl substituents In addition, six new derivatives of 2,3-dihydropyridine-4 (1H) - one have been synthesized, and some of them have been selected as lead compounds for further biological activity study (scheme3) (photo source: Green Chemistry) the scope of azadiels alder reaction catalyzed by fluorenone is not limited to the synthesis of 2,3-dihydropyridine-4 (1H) - one derivatives, but also can be used to synthesize other heterocycles (scheme 4) (photo source: Green Chemistry) next, the author examined the effects of catalyst, air and light source on the reaction The results showed that the reaction did not take place without light or photocatalyst Singlet oxygen in the air, as an essential electron mediator, can further improve the reaction yield In addition, the effects of different quenching agents (Table 1): when BHT or tempo is added to the reaction mixture, the reaction is terminated, which proves that the reaction goes through free radical pathway; CuCl2 is added After adding sodium azide, the yield of the reaction decreased, which indicated that singlet oxygen or active oxygen participated in the reaction (photo source: Green Chemistry) in order to further study the reaction mechanism, the author carried out the stern Volmer quenching experiment and quenched the excited state of the photocatalyst by trans anisole brain With the increase of trans anethole (1a) concentration, the light emission decreased significantly; in the presence of different concentrations of 2,3-dimethyl-1,3-butadiene, the light emission did not change Based on the above experimental results, the author proposed the reaction mechanism of visible light mediated D-A and azad-a (Figure 2) Firstly, photocatalyst is excited to photoexcited state by visible light Then, free radical cation 1a · + was obtained by single electron transfer (set) in 1a, and then [4 + 2] cycloaddition was carried out with diene to obtain free radical cation product 1c · + Then, 1c · + receives an electron of another equivalent 1a, and obtains the final product (1c) through the chain growth step At the same time, oxygen is also partly involved in the electron supply At this time, the role of air / oxygen is to transform the reduced photocatalyst into the original state (photo source: Green Chemistry) cyclobutane derivatives are widely found in active natural products (such as lignans and Neolignans) and drug molecules (scheme5a) The author obtained a variety of cyclobutane derivatives (scheme 5b) by [2 + 2] cycloaddition promoted by fluorenone catalyst In addition, the catalyst showed not only the activity of dimerization of olefins (1D), but also the excellent reactivity of isomerization of olefins (2D) (photo source: Green Chemistry) conclusion: shoubhik Das team developed the visible light mediated Diels alder and azadiels alder reactions with fluorenone as catalyst The catalyst is cheap and easy to obtain, and the reaction has a wide range of substrates In addition, the function of catalyst and oxygen was revealed through experimental study, and the reasonable reaction mechanism was put forward.