Palladium-Catalyzed Synthesis of 3-Indolecarboxylic Acid Derivatives

Abstract

Indoles having an ester functionality in the 3-position were prepared from 2-(2-nitrophenyl)propenoic acid derivatives via a palladium-catalyzed reductive N-heteroannulation using carbon monoxide as the ultimate reducing agent. The starting materials were prepared either by a Stille coupling of 2-halo-1-nitrobenzenes with ethyl 2-(tributylstannyl)-2-propenoate or by vicarious nucleophilic substitution of nitrobenzenes followed by a Knoevenageltype condensation with an aldehyde. Synthesis of an example of a 3-nitrile-and a 3-sulfone-substituted indole is also described using the same type of methodologies.

Transition Metal Catalyzed Reductive Cyclization Reactions of Nitroarenes and Nitroalkenes

“…The effect of electronwithdrawing groups on the vinyl group was investigated by first examining the reactivity of a series of compounds having the −COOMe, −COO t Bu, or −SO 2 Ph in the α position (Scheme ) …”

“…When the electronwithdrawing group was a cyano group and a pentyl group was present on the vinyl group, the synthesis of the indole was accompanied by the formation of a minor amount of quinoline (Scheme ) …”

A General Synthesis of Indole‐3‐carboxylic Esters by Palladium‐Catalyzed Direct Oxidative Carbonylation of 2‐Alkynylaniline Derivatives

“…The combined organic phases were dried with Na 2 SO 4 . GC-MS: m/z (%) = 363 (27) (95), 284 (100), 206 (55), 204 (30), 191 (18), 190 (17), 176 (9), 164 (20), 163 (18), 91 (57), 65 (17). ( 7, 139.2, 132.2, 131.4, 130.0, 128.7, 128.37, 128.18, 127.2, 127.1, 123.3, 116.7, 110.0, 107.6, 95.3, 86.1, 47.7 ppm.…”

“…[10] Moreover, these compounds have proved to be valuable synthetic intermediates for the preparation of different indole derivatives. [12] More recently, several novel approaches have been developed, mainly based on cyclization reactions and transition-metal catalysis, which include the intramolecular Pd-catalyzed condensation of halophenylenamino esters, [13] the DMAP-promoted reaction between hand, under similar conditions, but in the presence of HC(OMe) 3 , 2-alkynylanilines bearing an internal triple bond and a primary amino group (7) suitably substituted arylhydroxylamines and methyl propiolate, [14] the Pd 0 -catalyzed intramolecular α-arylation of β-(2-iodoanilino) esters, [15] the Cu I -catalyzed intramolecular amination of (2-bromophenyl)acetates, [16] and the Pd 0catalyzed reductive cyclization of 2-(2-nitrophenyl)acrylates, [17] among others. More specifically, compounds belonging to the sub-class of 5-oxyindole-3-carboxylic ester have been prepared by a classical method, involving the reaction between benzoquinone and β-aminocrotonic esters (Nenitzescu reaction).…”

Synthesis of 2‐Arylacrylates from Pyruvate by Tosylhydrazide‐Promoted Pd‐Catalyzed Coupling with Aryl Halides

“…For instance, 2-arylacrylates provide the main entry into the optically active version of prophens (a-arylpropionic acids), [3] the widely employed nonsteroidal anti-inflammatory agents. Moreover, these structures are activated olefins that are continuously employed as Michael acceptors, [4] dienophiles, [5] dipolarophiles, [6] alkenes for Heck and sequential Pd-catalyzed reactions, [7] intermediates in heterocyclic synthesis, [8] intermediates in the synthesis of cyclopropane carboxylic acids with biological activity, [9] and key fragments to generate diversity in drug discovery programs. [10] While the classical method for the synthesis of 2-arylacrylates is the condensation of the corresponding arylacetate with paraformaldehyde, [11,12] more recently, these systems have been prepared through different Pd-catalyzed crosscoupling reactions: Suzuki cross-couplings with 2-chloracrylates, [13] and alkenyl boronates, [14] Negishi reaction with 2-metallated acrylates, [15] and Pd-catalyzed carbonylation of arylvinyl bromides.…”