Acie of Frank glorius group: palladium catalyzed bifunctional reaction of olefins for the construction of all carbon quaternary carbon centers

Bifunctional reaction is a kind of effective method to construct complex molecular skeleton by a single step For the long-term challenges of this kind of reactions, such as β - hydrogen elimination side reactions of intermediate metal species, it can be solved by ligand design, substrate design or pre use transition metals At present, a lot of methods have been reported to obtain high-value ring skeleton through intramolecular form, but there are still few reports for multi substituted olefins The difficulty lies in the large steric repulsion of polysubstituted alkenes or the rapid elimination of β - hydrogen, which makes it difficult to form C (SP 3) - metal species a (scheme 1a) In addition, the reported methods are only suitable for one kind of aryl or alkyl electrophilic reagents, while the common methods for both kinds of substrates are rare Palladium catalyzed cross coupling reactions for the construction of carbon carbon bonds or carbon heterobonds are very mature methods, which usually go through two electron processes However, there are few reports on the process of free radical intermediates including monovalent palladium species Recently, several methods using palladium as a single electron donor have been reported Single electron transfer from palladium species can be initiated by thermodynamics or photoexcitation Recently, a team of Professor Frank glorius from the University of Minster in Germany reported that palladium photocatalyst can generate free radical intermediates through single electron transfer process, which can be used for the bifunctional reaction of three or four substituted alkenes to build quaternary carbon centers Related results were recently published in angew Chem Int ed (DOI: 10.1002 / anie 201911012) (photo source: angew Chem Int ed.) Firstly, the author used 2-bromophenol (1) and styrene (2) substituted by isopentenyl as model substrates for condition investigation (Table 1) The optimum reaction conditions are as follows: PD (PPh3) 4 as catalyst, xantphos as ligand, potassium carbonate as base, 1,4-dioxane as solvent and blue light as light source Classical ruthenium or iridium photocatalysts can not catalyze the reaction, which highlights the uniqueness of palladium catalyst excited by visible light The investigation results of the free radical trapping agent tempo confirmed that the reaction was via the free radical process (scheme 1c) Then, the author investigated the range of substrates (scheme 2) For all substrates, the E / Z selectivity was more than 99:1 Firstly, the effects of different substituents on alkenes are investigated The reaction is suitable for the four or six membered rings containing heteroatoms (4 - 8) For the substrates containing adamantyl (9) and acyclic substituents (10), the products can be obtained Tetrasubstituted olefin substrates produce products with two consecutive quaternary carbon centers (11 - 12) The effect of substituents on brominated aromatic rings was investigated The substituents with electron donor or electron acceptor groups can give medium to excellent yields (17-33) Some aromatic heterocycles, which play an important role in medicine, are also suitable (image source: angelw Chem Int ed.) next, the author continued to investigate more challenging alkylelectrophilic reagents (scheme 3), which are slow in oxidative addition and rapid in β - hydrogen elimination in palladium catalyzed reactions Tetrahydrofuran, carbonate compounds, pyrrolidine and piperidine all gave good yields (40 - 46) The reaction was also suitable for the substrate (47) of pyrrolidine, although the yield was low (18%) (image source: angelw Chem Int ed.) next, the author examined the acceptor olefin (scheme 4) The reaction conditions (48 - 59) are suitable for the substitution of styrene substrates by electron donor, electron acceptor or heterocycle Interestingly, for the α - methylstyrene substrate, the end olefin product (59) is obtained instead of the endoolefin product which is more stable in thermodynamics Acrylamide is also suitable for this reaction (60) (image source: angelw Chem Int ed.) finally, the author conducted a derivative operation of the product to show its application value in synthesis (scheme 5a) The product can be further converted into hydrogenation product (61), ozonation product (62), Suzuki miyaara coupling product (63) and epoxidation product (64) A neuroactive compound 67 was also synthesized by this method Starting from 2-Bromoaniline which is cheap and easy to obtain, 67 can be obtained by four linear steps, greatly shortening the previous synthesis step (scheme 5b) (photo source: angelw Chem Int ed.) Summary: Frank glorius group reported that palladium catalyst, as a non classical photocatalyst, is used for the bifunctional reaction of three or four substituted olefins The reaction is suitable for both alkyl and aryl bromides, and one or two consecutive quaternary carbon centers can be constructed This provides a fast and convenient method for the synthesis of complex compounds and large steric ring skeleton.