The Directed ortho Metalation (DoM)–Cross-Coupling Connection: Synthesis of Polyfunctional Biaryls

Abstract

A comparative evaluation of the combined directed ortho metalation (DoM)–Suzuki–Miyaura and DoM–Negishi cross-coupling reactions with aryl triflates for the synthesis of substituted biaryls is described. Both ortho-zinc and ortho-boron aryl directed metalation group (DMG = CON(i-Pr)2, OCONEt2, OMOM, NHBoc) substrates were evaluated. The superiority of the DoM–Negishi over the DoM–Suzuki–Miyaura reaction in operational convenience and mild reaction conditions is noted. Orthogonal Negishi and Suzuki–Miyaura with Corriu–Kumada reactions for the synthesis of a teraryl derivative is also reported.

The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update

“…The leading hierarchical position of the O -carbamate DMG strongly classifies it as a worthy choice for the regioselective construction of substituted aromatics by D o M chemistry, especially for substrates with Lewis acid stability requirements (Table ). Of the ranked positions 2, 3, and 4, the mildly acid sensitive O -DMGs, OMOM (2-methoxymethyl ether), have experienced the most utility. ,− Conversely, due to reactivity and convenience, , it is unclear why OMEM (2-methoxyethoxymethyl ether) and OTHP (tetrahydropyranyl ether) have not been more widely tested as DMGs. It is interesting to note that the addition of 0.5 mol % LiCl as a catalyst slows down the lithiation of O -carbamates compared to other DMGs, especially halides …”

“… 85 Of the ranked positions 2, 3, and 4, the mildly acid sensitive O -DMGs, OMOM (2-methoxymethyl ether), have experienced the most utility. 18 , 120 − 124 Conversely, due to reactivity and convenience, 125 , 126 it is unclear why OMEM (2-methoxyethoxymethyl ether) and OTHP (tetrahydropyranyl ether) have not been more widely tested as DMGs. It is interesting to note that the addition of 0.5 mol % LiCl as a catalyst slows down the lithiation of O -carbamates compared to other DMGs, especially halides.…”

Recent Advances in the Synthesis of 5-(Hetero)aryl Uracil Derivatives

“…Quesnelle et al combined directed ortho -metalation (DoM)/Suzuki–Miyaura and DoM/Negishi cross-coupling reactions with aryl triflates to prepare a diverse range of substituted biaryls. 56 During this process, they achieved a rapid synthesis of the 5-aryluracil 21 through the Pd(PPh 3 ) 4 -catalyzed coupling of 5-triflate-substituted uracil 18 with the arylzinc chloride 19 or boronic acid 20 (Scheme 8 ). Interestingly, when the commonly used Ni(acac) 2 was applied in the reaction with 19 , none of the desired product was observed.…”