Preparation of Organic Sodium Compounds.
Organosodium compounds in Negishi and Suzuki-Miyaura reactions
Organosodium compounds prepared by the above method can be transmetallized with ZnCl2-TMEDA (which is more stable to water vapor than ZnCl2) to obtain organozinc reagents, which is much cheaper and easier to handle than going through bromine or iodine substitutes. The latter can be further Negishi coupled to another molecule of aryl chloride substituent catalyzed by the catalyst Pd-PEPPSI-IPr developed by Valente et al. This approach allows the “one-pot” synthesis of large-site-resistance bis-aryl compounds (3b-3g) in a reaction that does not specifically require the electronic properties of the aryl chloro-substituents (3j, 3o, 3p, and 3s); sensitive functional groups such as alkoxycarbonyls (3i, 3p, and 3t) or cyano groups (3u) are well compatible with the reaction. . The conversion number of the reaction can be as high as 920 (0.1 mol% catalyst to give 3i in 92% yield), and it can even be synthesized on a gram scale (e.g., 3i). Alkyl chloro-substituents (3r, 3s) and alkenyl chloro-substituents (3q) can also participate in the reaction. It is worth mentioning that aromatic heterocyclic substrates such as benzofuran and benzothiophene can be directly
deprotonated in the presence of NaTMP (TMP: 2,2,6,6-tetramethylpiperidine) to give the corresponding aryl sodium compounds, which in turn undergo Negishi reactions (3t, 3u).
Negishi reaction involving organic sodium compounds. Image credit: Nat. Catal.
Similarly, the reaction of these aryl sodium compounds with boronic acid esters such as MeOBpin, B(OMe)3 and i-PrOBpin converts them into the corresponding aryl boronic acid esters, which in turn can undergo a Suzuki-Miyaura reaction with another molecule of aryl chloro-substituent to give the diaryl compounds under the catalyst of Pd-PEPPSI-IPr. It is worth noting that this reaction can also be realized as a “one-pot method” and does not require the addition of exogenous bases, since the reaction of aryl sodium with MeOBpin releases NaOMe, and a slight excess of sodium/paraffin oil dispersion reacts with the water added in the coupling reaction to form NaOH.
Suzuki-Miyaura reaction involving aryl sodium compounds
Direct use of aryl sodium for cross-coupling of aryl halides
Fañanás-Mastral et al. have found that 2,6-dimethoxyphenyl lithium can be coupled with 1-naphthyl bromide catalyzed by Pd-PEPPSI-IPent at room temperature to give 5a in 94% yield.Therefore, the researchers also subjected the prepared aryl sodium compounds to the same reaction and found that all of them were able to cross-couple with another molecule of the aryl chloro or bromo substituents to give the diaryl compounds (except for p-methylchlorobenzene) in very high yields. Without the presence of a catalyst, the reaction also gave a small amount of product, possibly undergoing a phenylalkyne intermediate state resulting in the product in a regiosemic
