ACS catalyst: nickel catalyzed reductive cracking of C − O bond of anisole derivatives

Methoxy group is a common functional group When it is linked with aromatic ring, it will produce obvious electron induction effect, which makes the substitution reaction of aromatic ring take place in ortho and para position In addition, the methoxy group on the aromatic ring can be used as the ortho guiding group in the catalytic reactions of lithium and transition metals and other para guiding groups in the process of aromatic substitution Therefore, it is important for organic synthesis to develop an effective method to remove methoxyl from aromatic ring to utilize other properties of aromatic ring Recently, the team of Mamoru tobisu and Naoto Chatani, University of Osaka, Japan, reported the reduction cracking of C-O bond in anisole Derivatives Catalyzed by nickel with diisopropylaminoborane as reducing agent The related article was published in ACS Catal And the paper was entitled "Nickel-Catalyzed Reductive Cleavage of Carbon - Oxygen Bonds in Anisole Derivatives Using Diisopropylaminoborane" (DOI: 10.1021/acscatal.8b02009) In the presence of Ni (COD) 2, imes me and NaOAc, the effect of reducing agent on the reaction of 4-tert-butylafennel (2a) was investigated By selecting a series of reducing agents, the author found that the highest yield of 3A was obtained by using excessive diisopropylaminoborane (1a) in toluene (source: ACS catalyst.) next, the authors examined different ligands (Fig b) The results showed that imes me was the best ligand when diisopropylaminoborane was used as reducing agent (source: ACS catalyst.) in order to evaluate the superiority of the catalytic system, the author compares the new method (method a) with the three previously reported methods (method B-D) (Table 2) The results show that method a is more feasible than the other three methods Even the relatively low activity biphenyl substrate 2G can produce reductive cracking reaction at 60 ° C, while method B − D can not form any ideal product at this temperature (source: ACS catalyst.) later, the author studied the substrate range of this kind of reductive cracking reaction in more detail (Table 3) The results show that the reaction is not only suitable for π - extended aryl ethers such as naphthyl and diphenyl ethers, but also for mono - and heterocyclic ethers containing various functional groups (source: ACS catalyst.) then, the author carried out a series of deuterium labeling experiments to trace the source of hydrogen atom in the reduction product (scheme 2) The results show that the hydrogen atom of the substituted methoxy is likely to come from 1a (source: ACS catalyst.) finally, the author proposed a response mechanism (scheme 3) 1A can reduce ketone without catalyst, and make the oxygen atom of anisole coordinate with boron atom of 1a to form complex a the formation of a will reduce the electronic density of C − O bond of anisole, thus promoting the oxidation addition of C − O bond and Ni (imes me) n (n = 1 or 2) to form intermediate B Then the hydrogen atom migrates from boron to nickel to get compound D the author thinks that this process takes place in the intramolecular way through C The deoxidation product e was eliminated by reduction of D, which was accompanied by the regeneration of nickel catalyst (source: ACS catalyst.) Summary: the reduction cracking reaction of C − O bond of anisole derivative catalyzed by nickel has been developed The reaction uses diisopropylaminoborane as reducing agent and is widely applicable to substrates containing various functional groups In addition, this reaction makes methoxy group a removable guiding group, which provides many possibilities for the later functionalization of common anisole derivatives.