Chem. Sci.: the Procter research group of University of Manchester realizes the cross coupling of sulfoxide mediated phenol oxidation.

The catalytic cross coupling of aryl halides and organometallic reagents is an effective tool for the synthesis of biaryl (scheme 1a) Recently, oxidative C-H / C-H coupling of non pre functionalized substrates has become a new alternative (scheme 1b), but its development is still a challenge Therefore, the development of C-H / C-H coupling with selective non-metallic catalysis is of great significance Phenols, especially the biarylethenes derived from asymmetric phenols, are widely found in nature, biomaterials and catalysts The preparation methods usually require multi-step functional grouping or protecting group operation and / or the use of metals Therefore, non-metallic oxidative coupling of unprotected phenols has attracted attention, but avoiding self coupling is full of challenges (scheme1c) At present, scheme 1D of phenol has been realized by other methods Sulfoxide can be used to change the reactivity of phenols and provide another method for their oxidative coupling Recently, the David J Procter research group of University of Manchester has developed a non metal oxidation cross coupling method of phenol with various nucleophilic agents (such as other phenols, aromatics and 1,3- two ketones) (Scheme 1E), used for the synthesis of aryl, 2- aryl -1,3- two carbonyl compounds and benzofurans The results were published in the recent Chem Sci (DOI: 10.1039/C9SC05668H) (photo source: chem SCI.) oxidative cross coupling of phenol with other phenols, phenol derivatives and aromatics: firstly, the author treated phenol 1A with sulfoxide 4a, activated by trifluoroacetic anhydride (tfaa), and then added 2a to obtain coupling product 3a in 91% yield 2-naphthol, 1-naphthol, phenol and their methyl ether derivatives containing bromine, methoxy, phenyl, cyano and ester groups at positions 3, 6 and 7 can tolerate the coupling reaction (scheme 2) In addition, pyrene was coupled with 1a to form 3R There are also many kinds of phenol coupling ligands (AR 1), whose neighbors are coupled with a series of nucleophilic ligands to obtain corresponding products Under the standard conditions, the yield of 3AB 'can be increased to 46% by treating 4-methoxyphenol with 1,2,4-trimethoxybenzene, and 80% by using 2.2eq Sulfoxide 4A and 2.0eq 1,2,4-trimethoxybenzene Interestingly, by adjusting the coupling conditions, single or double coupling products can be obtained; when CH2Cl2 / TFA (1:1) is used as solvent, it is favorable for the formation of single aromatization products Finally, the oxidative coupling can be carried out in gram scale (photo source: chem SCI.) oxidative coupling of phenols with 1,3-dione: 1,3-dicarbonyl compounds can be used as a second nucleophilic mate (scheme 3) 6A was obtained by 1,3-diphenylpropane-1,3-dione treatment for 1a Benzofuran products can be obtained by cyclization of ortho coupling products For example, 4-methoxyphenol can produce aryl [b] benzofuran 6e (picture source: chem SCI.) iterative coupling of three nucleophiles: Based on the interest in the synthesis of triaryl compounds 3AB 'and 3aC' (scheme 2), the author conceives an iterative process, that is, phenol and two different nucleophiles successively undergo non-metallic oxidative coupling (scheme 4) For example, after coupling 4-methoxyphenol with 1,2,4-trimethoxybenzene to obtain 3AB, asymmetric diarylphenol 7a can be obtained through 1,3-dimethoxybenzene treatment 1,3-diphenylpropane-1,3-dione can also be used as a third nucleophilic mate, and C 7-arylated benzofuran 7C and 7h were obtained (photo source: chem SCI.) study on the mechanism of oxidative cross coupling reaction: Based on the above research, the author proposed the possible mechanism of oxidative cross coupling (scheme 5a): firstly, sulfoxide 4A was activated by tfaa to obtain acyloxysulfonium SALT II, and then it reacted with phenol coupling conjugate to form aryloxysulfonium salt I through the interrupted Pummerer reaction Subsequently, the attack of the second mate on the neighbor or para position of the first mate resulted in the formation of C-C bond and the release of 3-methylbenzothiophene By means of scheme 5b, the important role of hydroxyl group in the first mate was verified, and the activation of phenol was carried out through intermediate I However, the author is unable to detect or separate the intermediate, and further study on the mechanism of phenol activation is needed In addition, the feeding sequence of the two nucleophilic ligands was found to be critical (scheme 5C), indicating that the formation of aryloxy sulfonium salt from the activated sulfoxide I and the first phenol ligands was fast and irreversible, and that the aryloxy sulfonium salt intermediates had significantly different reactivity (picture source: chem SCI.) conclusion: David J Procter team developed a non-metallic oxidative cross coupling method between sulfoxide mediated phenol and various nucleophiles, such as phenol, 1,3-dione and aromatics The key point of the cross coupling is to capture and reverse the reactivity of the first nucleophile by intermittent Pummerer reaction before coupling with the second nucleophile In addition, no self coupling was observed in the coupling reaction, which avoided the replacement of Pummerer reaction and rearrangement process.