Comparison of the Suzuki cross-coupling reactions of 4,7-dichloroquinoline and 7-chloro-4-iodoquinoline with arylboronic acids using phosphine-free palladium catalysis in water

Abstract

4,7-Dichloroquinoline (1a) and 7-chloro-4-iodoquinoline (1b) undergo Suzuki cross-coupling reactions with arylboronic acids catalyzed by phosphine-free palladium acetate in boiling water. Using phenylboronic acid (2), the reaction of 1a provides 7-chloro-4-phenylquinoline (3) (78%) together with diphenylquinoline (4) (12%), while 1b reacts in a much more regioselective fashion and provides 3 in 98% isolated yield. Although 1b undergoes a more regioselective Suzuki reaction than 1a, additional important observations are that the overall reaction of 1b with 2 is three times slower than 1a and that the reaction occurs in the absence of tetrabutylammonium bromide. Using optimized reaction conditions, a variety of aryl and vinylboronic acids undergo regioselective Suzuki cross-coupling with 1b to provide the products 7, 10, and 11 in good to excellent yield.Résumé : La 4,7-dichloroquinoléine (1a) et la 7-chloro-4-iodoquinoléine (1b) subissent des réactions de couplage de Suzuki avec les acides arylboroniques qui sont catalysées par de l'acétate de palladium sans phosphine dans de l'eau bouillante. Avec l'acide phénylboronique (2), la réaction du composé 1a fournit la 7-chloro-4-phénylquinoléine (3) (78%) aux côtés de diphénylquinoléine (4) (12%) alors que le composé 1b réagit d'une façon beaucoup plus régiosé-lective et fournit le composé 3 avec un rendement de 98% en produit isolé. Même si le composé 1b donne lieu à une réaction de Suzuki plus régiosélective que celle du composé 1a, des observations importantes additionnelles sont que la vitesse globale du composé 1b avec 2 est trois fois plus lente que celle du composé 1a et que la réaction se produit en l'absence de bromure de tétrabutylammonium. Utilisant des conditions réactionnelles optimisées, une variété d'acides aryl-et vinylboroniques donnent lieu à des réactions régiosélectives de couplage croisé de Suzuki avec le composé 1b et elles fournissent les produits 7, 10 et 11 avec des rendements allant de bons à excellents.

Studies of one-pot double couplings on dibromoquinolines

“…(Scheme 1) 4,7-dichloroquinoline has been studied by two different groups, with both reporting good selectivity for coupling at the 4 position. 8 In one case, the initial Suzuki coupling at C4 was the followed by a second coupling reaction at C7 to afford product 1 in 69% yield over the two steps. 9 …”

Arylboronic Acids and Arylpinacolboronate Esters in Suzuki Coupling Reactions Involving Indoles. Partner Role Swapping and Heterocycle Protection

“…It has, consequently, been widely applied in the formation of biaryl compounds where it usually involves the Pd(0)-mediated linking of an aryl halide with an arylboronic acid or arylboronate ester. The mechanism by which it proceeds is known to be complex in its details, − and the oxidative addition, ,, transmetalation, , and reductive elimination steps have all been reported to be rate-determining in certain cases. Nonetheless, there is broad consensus that the main stages involved are those shown in Scheme .…”

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

“…It was also observed that 7‐chloro‐4‐iodoquinoline ( 380 ) underwent Pd(OAc) 2 ‐catalyzed Suzuki–Miyaura monoarylation in a more site‐selective fashion with a variety of (hetero)arylboronic acids and an alkenylboronic acid in the absence of ( n‐ Bu) 4 NBr to give 4‐substituted 7‐chloroquinolines 384 in yields ranging from 58 to 97% (Scheme ). However, the rate of the reaction of 381 with boronic acid 19 was three times lower than that of 372 127…”

“…In 2004, Friesen and Trimble127 found that 4,7‐dichloroquinoline ( 372 ) underwent Pd(OAc) 2 ‐catalyzed site‐selective arylation at the activated C‐4 position by treatment with 1.1 equiv. of phenylboronic acid ( 19 ) in the presence of 0.25 equiv.…”