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Many parameters are still required to be investigated in order to describe an efficient and selective catalytic C–N bond formation at a high-valent Bi platform. At this stage, we have developed a high-yielding catalytic cross-coupling method by using NFSI as both an oxidant and a coupling partner. This protocol produces both C(sp2)–N and C(sp2)–O coupling products. In order to control the chemoselectivity, we have investigated the influence of the ligand scaffold of the bismuth catalyst, which resulted in only small change in the product ratios. Furthermore, we have started investigating modified NFSI analogues and their influence on product formation. Further studies have to be carried out to synthesize analogues of NFSI with EDGs as well as determine the accurate yields of products while using these substituted oxidants. In addition, the influence on the reaction outcome of various other parameters (i.e. different bases or other additives) has to be evaluated to determine if this platform can be modified to yield either of the products selectively.
Thinking about the results discussed throughout section 4.3, we have observed that in the pyridone case, there are no chemoselectivity issues within the same method, besides only a couple of distinct examples. However, both in saccharin and dibenzenesulfonamide cases, there is no clear selectivity between aryl–N or aryl–O cross-coupling. Considering the Curtin-Hammett principle,412, 413 the two pathways to form both cross-coupling products have very small ΔΔG‡. Most likely the Bi(V) complexes from which the RE event happen are very similar in energy, suggesting that both activation barriers for nitrogen or oxygen attack on the aryl ring are also similar in energy (Figure 4.9).
This is rather unusual, since these two atoms have different electronegativities. Nitrogen in both reagents has an additional electron withdrawing functionality (carbonyl or sulfonyl) compared to oxygen, which reduces the electron density on the nitrogen. As a result, it makes it electronically more similar to the oxygen atom in either carbonyl or sulfone moiety. If this is the case, to achieve the chemoselectivity in these platforms we should aim to influence one atom without affecting the other and since they are both positioned within the same functionality, this becomes a difficult task. If the total selectivity cannot be achieved, we could still use the obtained results to fundamentally investigate the behavior of high-valent bismuth.
If the abovementioned method of coupling arylboronic acids with NFSI analogues cannot be modified to be chemoselective, other possible coupling partners for the C–N cross-coupling have to be evaluated. Taking into consideration the hypothesis described in the previous paragraph, we should aim at candidates where nitrogen atom does not have an additional electron withdrawing functionality attached to it, similar to pyridone. One possible class of candidates is bisarylsulfoximines (Figure 4.10(A)). In these molecules, we have one of each oxygen and nitrogen atoms in the tetrahedral geometry on the high-valent sulfur atom, which should allow the formation of a 5-membered transition state in the potential reductive elimination event. In addition, there already are precedents of cross-couplings between arylboronic acids and bisarylsulfoximines catalyzed by copper.414 Furthermore, the method to synthesize of N-chloro-diphenylsulfoximine has already been published.415 The synthesis N–F analogue, however, has not yet been reported. Therefore we could investigate bisarylsulfoximines as coupling partners if at least one of the three following criteria are met: a) if we want to use N–Cl oxidants, we have to achieve transmetallation after the reductive elimination event (similar to N-chlorosaccharin case); b) synthesize and purify N-fluoro-diphenylsulfoximine; c) use bisarylsulfoximine in combination with a base and an external compatible oxidant, similar to the triflation protocol.
Other potential class of candidates are alkyl/aryl sulfonamides (Figure 4.10(B)). Here again, the sulfonamide moiety provides means for the 5-membered transition state in the assumed reductive elimination step. Furthermore, the electronics of nitrogen atom can be fine-tuned by modifying the substituents on either of the aryl rings. Similar coupling between arylboronic acid and sulfonamide has been reported while using copper salt and additional oxidant.416 In addition, synthetic protocols to produce the N–F reagents of such sulfonamides have already been reported and they were shown to be potential oxidants.417, 418
In conclusion, there are multiple different directions to develop a selective high-valent bismuth catalyzed C(sp2)–N cross-coupling protocol. Further development of aryl–N coupling platform while using NFSI or N-chlorosaccharin, as well as numerous possibilities of other nitrogen containing ligands give us chances to explore and cast more light on the cross-coupling capabilities of high-valent bismuth.
