Carbonylative Suzuki-Miyaura couplings of sterically hindered aryl halides: Synthesis of 2-aroylbenzoate derivatives

TY - JOUR

T1 - Carbonylative Suzuki-Miyaura couplings of sterically hindered aryl halides

T2 - Synthesis of 2-aroylbenzoate derivatives

AU - Ismael, Aya

AU - Skrydstrup, Troels

AU - Bayer, Annette

PY - 2020

Y1 - 2020

N2 - We have developed a carbonylative approach to the synthesis of diversely substituted 2-aroylbenzoate esters featuring a new protocol for the carbonylative coupling of aryl bromides with boronic acids and a new strategy to favour carbonylative over non-carbonylative reactions. Two different synthetic pathways-(i) the alkoxycarbonylation of 2-bromo benzophenones and (ii) the carbonylative Suzuki-Miyaura coupling of 2-bromobenzoate esters-were evaluated. The latter approach provided a broader substrate tolerance, and thus was the preferred pathway. We observed that 2-substituted aryl bromides were challenging substrates for carbonylative chemistry favouring the non-carbonylative pathway. However, we found that carbonylative Suzuki-Miyaura couplings can be improved by slow addition of the boronic acid, suppressing the unwanted direct Suzuki coupling and, thus increasing the yield of the carbonylative reaction.

AB - We have developed a carbonylative approach to the synthesis of diversely substituted 2-aroylbenzoate esters featuring a new protocol for the carbonylative coupling of aryl bromides with boronic acids and a new strategy to favour carbonylative over non-carbonylative reactions. Two different synthetic pathways-(i) the alkoxycarbonylation of 2-bromo benzophenones and (ii) the carbonylative Suzuki-Miyaura coupling of 2-bromobenzoate esters-were evaluated. The latter approach provided a broader substrate tolerance, and thus was the preferred pathway. We observed that 2-substituted aryl bromides were challenging substrates for carbonylative chemistry favouring the non-carbonylative pathway. However, we found that carbonylative Suzuki-Miyaura couplings can be improved by slow addition of the boronic acid, suppressing the unwanted direct Suzuki coupling and, thus increasing the yield of the carbonylative reaction.

UR - http://www.scopus.com/inward/record.url?scp=85081146342&partnerID=8YFLogxK

U2 - 10.1039/d0ob00044b

DO - 10.1039/d0ob00044b

M3 - Journal article

C2 - 32065204

AN - SCOPUS:85081146342

SN - 1477-0520

VL - 18

SP - 1754

EP - 1759

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 9

ER -