A Tandem “On‐Palladium” Heck–Jeffery Amination Route Toward the Synthesis of Functionalized Indole‐2‐carboxylates

Abstract

A direct synthesis of functionalized indole‐2‐carboxylates involving a PdII‐catalyzed annulation of ortho‐iodoanilines onto a vinyl ether is described. The reaction mechanism is shown to be distinct from a stepwise Heck, intramolecular amination pathway, likely involving a tandem “on‐palladium” Heck–Jeffery amination process incorporating a novel intramolecular amination step.

A Domino Heck Coupling–Cyclization–Dehydrogenative Strategy for the One-Pot Synthesis of Quinolines

“…[36][37][38][39][40][41][42][43] Particularly, in Heck coupling reactions, palladium is an active catalyst when aryl iodides/bromides are used as synthetic precursors in couplings with various alkene partners. 44 Notably, there are only a limited number of investigations on palladium-based Jeffery-Heck reactions, [45][46][47][48] followed by the ensuing transformation of the resulting carbonyl compounds into the corresponding quinolines via a condensation/aromatization sequence. 49,50 In this context, in 1991, Larock et al initially synthesized four examples of quinolines by utilizing the palladium-catalyzed Jeffery-Heck reaction using toxic hexamethylphosphoramide (HMPA) as the solvent.…”

Tandem catalytic oxidative deacetylation of acetoacetic esters and heteroaromatic cyclizations

“…Data for 21: R f = 0.4 (hexane:EtOAc = 4: 1); 1 H NMR δ 1.47 (t, J = 7.2 Hz, 3H), 2.82 (s, 3H), 4.54 (q, J = 7.2 Hz, 2H), 7.47 (d,J = 8.8 Hz,1H),95 8.08 (d,J = 8.8 Hz,1H) ppm; 13 C NMR δ 14.2, 22.5, 62.4, 127.1, 127.4, 149.9, 162.5, 164.3 ppm;IR (KBr) 3274, 2989, 2941, 2100, 1723, 1589, 1473, 1446, 1382, 1339, 1275, 1227, 1148, 1085, 1017 ; HRMS (EI + ) calcd for C 8 H 10 N 2 O 2 166.0742, found 166.0743. 100 (22). To a stirred solution of 19 (0.13 g, 0.50 mmol) in a 9:1 (v:v) mixture of MeOH and H 2 O (10 mL) was added KOH (0.17 g, 3.00 mmol).…”

“…Ethyl 1H-indole-2-carboxylate (27). 22 The suspension of 25 (0.16 g, 0.67 mmol) and 10% Pd/C (70 mg, 0.067 mmol) in methanol (5 mL 13 C NMR δ 14.3,61.0,108.6,111.9,120.7,122.5,125.3,127.4,127.4,136.9,162.2 ppm. 105 Ethyl 4-(2-(ethoxycarbonyl)-3-oxobutyl)-3-nitrobenzoate (28).…”

Total synthesis of the cyanobacterial metabolite nostodione A: discovery of its antiparasitic activity against Toxoplasma gondii

“…Removal of the N-tosyl substituent was accomplished under mild conditions using TBAF. 11 Direct acylation on the deprotected phosphonate (12) now occurred smoothly with oxalyl chloride in diethyl ether yielding initially the monoacyl chloride derivative (13). Attempts at intramolecular acylation initially proved extremely challenging and a summary of select examples en-route to optimisation of this reaction is collected in Table S1 (ESI †).…”

“…Further elaboration on this lead compound toward the development of a novel potent and selective anti-toxoplasmosis agent and investigation of related antiprotozoal activity of nostodione A and analogues from functionalised indole-2-carboxylates 13 is currently in progress. These preliminary results also indicate interesting diversity in the structure-activity relationships (SAR) of the compounds relevant to the inhibition of host cell attachment and invasion by T. gondii tachyzoites.…”