TY - JOUR

T1 - One-Pot Synthesis of Xanthone by Carbonylative Suzuki Coupling Reaction

AU - Loureiro, Daniela R. P.

AU - Soares, Jose X.

AU - Maia, Ana

AU - Silva, Andre M. N.

AU - Rangel, Maria

AU - Azevedo, Carlos M. G.

AU - Hansen, Steffen

AU - Ulven, Trond

AU - Pinto, Madalena M. M.

AU - Reis, Salette

AU - Afonso, Carlos M. M.

PY - 2021

Y1 - 2021

N2 - Xanthone derivatives have a dibenzo-y-pyrone scaffold which has gained great interest in Medicinal Chemistry due to their diverse biological activities. Usually, its synthesis requires multi-step synthetic routes using harsh conditions and high catalyst loadings. In this communication, we report for the first time a one-pot synthesis of the xanthone scaffold based on a carbonylative Suzuki coupling. Iodophenol and (2-methoxyphenyl)boronic acid were coupled under carbon monoxide, generated from a carbon monoxide surrogate. An experimental data-based model was built to guide the reaction optimization. The optimized conditions were 1 mol% of a pincer complex as palladium catalyst, 5 equivalents of K2CO3 as base, and DMF:water (7 : 3) as solvent. The robustness of the synthetic method, namely in terms of the reactants scope, was also evaluated. This approach provided the xanthone scaffold in high yields and provided a deep insight into the carbonylative Suzuki couplings.

AB - Xanthone derivatives have a dibenzo-y-pyrone scaffold which has gained great interest in Medicinal Chemistry due to their diverse biological activities. Usually, its synthesis requires multi-step synthetic routes using harsh conditions and high catalyst loadings. In this communication, we report for the first time a one-pot synthesis of the xanthone scaffold based on a carbonylative Suzuki coupling. Iodophenol and (2-methoxyphenyl)boronic acid were coupled under carbon monoxide, generated from a carbon monoxide surrogate. An experimental data-based model was built to guide the reaction optimization. The optimized conditions were 1 mol% of a pincer complex as palladium catalyst, 5 equivalents of K2CO3 as base, and DMF:water (7 : 3) as solvent. The robustness of the synthetic method, namely in terms of the reactants scope, was also evaluated. This approach provided the xanthone scaffold in high yields and provided a deep insight into the carbonylative Suzuki couplings.

KW - xanthone

KW - synthetic methods

KW - optimization

KW - carbonylation

KW - design of experiments

KW - TRANSITION-METAL-FREE

KW - ARYL HALIDES

KW - ARYLBORONIC ACIDS

KW - CATALYZED CARBONYLATION

KW - DESIGN

KW - OPTIMIZATION

KW - DERIVATIVES

KW - TOSYLATES

KW - SELECTION

KW - PRESSURE

U2 - 10.1002/slct.202101394

DO - 10.1002/slct.202101394

M3 - Journal article

VL - 6

SP - 4511

EP - 4514

JO - ChemistrySelect

JF - ChemistrySelect

SN - 2365-6549

IS - 18

ER -