Coupling can be “Sodium” too!
The research of organic sodium reagents can be traced back to the 1840s and 1850s, when Frankland, Wanklyn and Wurtz reacted with alkyl halogenated substances and metallic sodium, speculating that alkyl sodium species might be formed, and the real synthesis of alkyl sodium was realized in the 1930s. However, due to the hazardous nature of metallic sodium, this method was difficult to apply synthetically, and instead organolithium reagents, dialkylzinc, dialkylmercury, and later Grignard’s reagents were used to participate in the relevant reactions. The application of organosodium reagents has also been limited to their use as nucleophilic reagents in reactions with electrophilic reagents such as carbon dioxide or carbonyl compounds. However, it is of great interest to industry because sodium is an alkali metal of very high abundance in the earth’s crust and oceans, and if its synthetic applications can be tapped, e.g., the use of organochlorine substitutes to prepare the corresponding organosodium reagents in place of
organolithium/grignard/organozinc reagents, etc., it will help to reduce the cost of the drug/chemical industry as well as improve the safety of production. There are three reasons for this: (1) most organolithium or Grignard reagents are now prepared by expensive bromine or iodine substitutes, whereas inexpensive chlorine substitutes have very low reactivity and often require very harsh conditions; (2) the preparation of organolithium or Grignard reagents requires very careful temperature control, e.g., butyl lithium has to be prepared at low temperatures, and magnesium metal has to be prepared in refluxing state; (3) the content of lithium in nature is is small and unevenly distributed, and the cost of lithium will increase as lithium batteries are consumed.
Recently, Kazuhiko Takai’s group at Okayama University in Japan published research results on the application of organic sodium reagents in Nature Catalysis. They found that sodium can be dispersed in paraffin oil to form a stable and easy-to-handle dispersion, from which it can be reacted with organic chlorides under mild conditions to form the corresponding organic sodium reactive species, which, like organolithium and Grignard’s reagent, undergoes transmetalation to obtain the corresponding zinc reagent or borate ester, which then undergoes a Negishi or Suzuki-Miyaura cross-coupling reaction. More interestingly, aryl sodium compounds can be directly coupled to aryl halides under palladium catalysis.
Preparation of organosodium reagents and their application in coupling reactions.
The form of the building block exists.
Cross-coupling with direct participation of aryl sodium compounds.
Summary
Kazuhiko Takai’s group reclaimed the long-dormant organic sodium reagents and verified their application in cross-coupling reactions. They obtained the corresponding organic sodium compounds by reacting sodium/paraffin oil dispersions with a variety of different inexpensive and readily available aryl chloro-substituents, which can be smoothly converted to the corresponding aryl zinc and aryl borate esters, which can then be used to participate in the Negishi and Suzuki-Miyaura cross-couplings, and thus can reduce the industrial cost. The authors also note that in the future they will further investigate whether inexpensive catalysts (e.g., iron catalysts) can catalyze these organosodium compounds for similar reactions.
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