C2‐Arylation of Substituted Pyridine N‐oxides with Heteroaryl Carboxylic Acids by Palladium‐Catalyzed Decarboxylative Coupling

Abstract

A palladium catalyzed CH activation/ortho‐arylation of heteroaryl‐N‐oxides through a decarboxylative coupling of heteroaryl carboxylic acids is described. Heterobiaryl‐N‐oxides, which are difficult to access by conventional methods, can be obtained in a single step. A wide range of functional groups, including metal‐susceptible groups, such as bromo and iodo, can be tolerated under the reaction condition. The regioselectivity with respect to both carboxylic acid and N‐oxide is excellent. Further, the N‐oxides were used as a tool to examine the efficiency of decarboxylative coupling compared with aryl halide coupling.

Recent Progress in Decarboxylative Oxidative Cross‐Coupling for Biaryl Synthesis

“…Another group of arenes that have proved to be reactive in C–H activation processes are pyridine N ‐oxides. Muthusubrumanian and co‐workers employed these substrates in decarboxylative coupling with heteroaromatic carboxylic acid derivatives (Scheme ) . Unfortunately, the use of simple benzoic acid derivatives was not reported.…”

Regioselective Decarboxylative Cross-Coupling of Carboxy Isoquinoline N-Oxides

“…In the current context where cross-coupling process remained a synthetic challenge due the instability of the organometallic species at the C- 1 or C- 3 positions of the isoquinoline core, several direct C 1 –H arylation methodologies has been actively developed, mainly from the N -oxide derivatives through (i) the direct C–H arylation under palladium catalysis with (pseudo)­halides or with carboxyarenes (Scheme , eq 1), (ii) the oxidative C–H/C–H cross-coupling devoid of prefunctionalization steps (Scheme , eq 2), , and (iii) the S N H-type reaction by the generation of aryl radicals from arylboronic acids (Scheme , eq 3). , In the context where only the (hetero)­arylation at the C- 1 position of the isoquinoline ring has been developed, the substitutive cross-coupling of prefunctionalized isoquinolines appeared as a reliable and appropriate method to fully control the selectivity at the C- 1 and C- 3 positions. Therefore, C- 1 and C- 3 carboxy isoquinolines have been selected as suitable substrates for regioselective catalytic cross-coupling reaction via the selective in situ generation of organometallic species by the transition metal-mediated extrusion of CO 2 .…”

The Acid-Free Cyclopropanol-Minisci Reaction Reveals the Catalytic Role of Silver–Pyridine Complexes

“…4-Methoxypyridine ( 10 ) gave the desired product only when Ag­(II)­(bipy) 2 ·S 2 O 8 was used. To our knowledge, this is the only example of direct functionalization of 4-methoxypyridine using a Minisci-type reaction . As expected, pyridines bearing electron-withdrawing groups ( 12 – 15 ) gave the best yields of products.…”