Nat. Commun.: Suzuki miyaara cross coupling reaction of aldehydes catalyzed by nickel

Transition metal catalyzed cross coupling has been widely used to construct a variety of C-C bonds Conventional cross coupling reactions require reactive electrophilic couples, such as organic halides or sulfonates, as well as exogenous bases to facilitate key metal transfer steps However, the reagent inevitably causes side reactions and limits the range of substrates It is of great significance to develop cheap, nontoxic and able to construct c-c-linked mate without alkali Recently, Professor Magnus rueping of the Institute of organic chemistry, Aachen University of technology, Germany, developed an unconventional Suzuki coupling reaction: in the absence of alkali, the nickel catalyzed aldehyde and organoboron reagent undergo cross coupling of benzoyl groups The transformation can tolerate the coupling of different (hetero) aryls in structure, and shows high reactivity and excellent functional group tolerance In addition, the scheme can be carried out in gram scale and successfully applied to the functionalization of complex bioactive molecules Relevant research results were published on nat.commun (DOI: 10.1038/s41467-019-09766-x) (source: Nat Commun.) rational design of Ni catalyzed diaryl coupling of aldehydes must avoid decarbonylation (I to II) caused by the oxidation of the C (acyl) - H bond of aldehydes to the acyl Ni (II) hydride produced by LNNI (0) Therefore, in order to avoid undesired reduction coupling and formation of aromatics III, the authors suggest that hydrogen extraction or transfer from acyl nickel (II) hydride to H-receptor will realize transfer metallization (I to IV) and inhibit decarbonylation reduction coupling pathway Subsequent aryl migration (IV to V) and reduction elimination will provide cross coupling products and regenerate the Ni catalyst Based on these considerations, the ideal h receptor needs (I) full compatibility; (II) ready to use; (III) dual function: it can not only inhibit reductive coupling through hydride extraction, but also promote transfer, so as to achieve alkali free conditions (fig.1c) Therefore, ketone is considered a possible h receptor because it meets all of these requirements DFT studies confirm this hypothesis (fig.1c) In order to optimize the reaction conditions, the author evaluated the reaction parameters in the presence of nickel / ligand catalytic system with nicotinaldehyde (1a) and neopentyl phenylborate (2a) as coupling partners and ketone as hydride acceptor (Fig 2) The results show that the combination of TFE (4a), Ni (COD) 2 and P (OCT) 3 can produce diaryl products in 77% yield without alkali The control experiment shows that catalyst, ligand and hydride receptor are the key to the success of this reaction (source: Nat Commun.) the reaction range of various aromatic and heteroaromatic borate nucleophiles with nicotine aldehyde (1a) was determined Various phenylborate substrates with electron donor or electron acceptor functional groups can be converted into the corresponding biaryl products in good yield The decarbonylation cross coupling reaction can be easily extended to heteroaromatic borates derived from (benzo) furan and (benzo) thiophene, and the corresponding product 3av-3aaa is obtained In addition, two examples of estrone and δ - tocopherol derivatives (3abb and 3acc) highlight the applicability of this method in complex molecular post modification A series of aldehydes, including phenyl, naphthyl, phenanthrene and fluorenyl aldehydes, are suitable as electrophilic coupling agents The tolerance of functional groups such as dioxocyclopentadiene, trifluoromethyl, Trifluoromethoxy and ester is good under the reaction conditions (source: Nat Commun.) mechanism the author elucidated the reaction mechanism through a series of experiments Isotope labeling experiments provide direct evidence for the occurrence of hydride transfer in cross coupling reactions (FIG 4A) KIE (kinetic isotope effect) experiments show that the process of C (acyl) - H insertion and hydride transfer is relatively fast (Fig 4b) It is suggested that the formation of biaryl products may go through the following processes: 1) oxidative addition of C (acyl) - H bonds of aldehydes to Ni; 2) hydrogen transfer and metal transfer; 3) aryl transfer and reduction elimination In addition, a detailed DFT calculation was carried out to support the proposed mechanism of nickel catalyzed aromatization of aldehydes (source: Nat Commun.) conclusion: Professor Magnus rueping, Institute of organic chemistry, Aachen University of technology, Germany, developed the decarbonylation aromatization of aldehydes and borates catalyzed by nickel In contrast to the classical cross coupling reaction, this method allows the use of cheap, nontoxic and easily available aldehydes as unconventional coupling electron acceptors, with a wide range of substrates, high chemical selectivity and scalability.