Pd(0)-Catalyzed Intramolecular Heck reaction of 2/3-Aryl(amino)methyl-3/2-bromoindoles: Syntheses of 3,4-Benzo[c]-β-carbolines, Benzo[4,5]isothiazolo[2,3-a]indole 5,5-Dioxides, and 1,2-Benzo[a]-γ-carbolines

Abstract

One-pot synthesis of 3,4-benzo[c]-β-carbolines was achieved from 2-aryl(tosylamino)methyl-3-bromoindoles via 10 mol % Pd(OAc) 2 /PPh 3 -mediated intramolecular Heck coupling using K 2 CO 3 as a base in DMF at 110 °C with concomitant aromatization through an elimination of tosylsulfinic acid. Under identical conditions, the isomeric 3-aryl(tosylamino)methyl-2bromoindoles upon intramolecular Heck reaction furnished benzo [4,5]isothiazolo[2,3-a]indole 5,5-dioxides instead of the expected γ-carbolines. However, synthesis of the expected γcarboline framework, 3-tosyl-6,9-dihydro-1,2-benzo[a]-γ-carbolines, could be achieved from 3-aryl(tosylamino)methyl-2bromoindoles containing a mesitylene sulfonyl unit as a protecting group on the indole nitrogen.

I2/DMSO mediated Cascade cyclization reaction of amino coumarins with aryl methyl ketones: Access to Dicoumarino‐fused [1,5]‐diazocine and pyrrolo‐coumarin scaffolds

“…]diazocine-6,7,14(8H)-trione (11) [32] An oven dried pressure tube containing a mixture of 0.1 mmol (53 mg) of (Z)-15-(4-bromophenyl)-6H,7H-dichromeno [4,3-b:4',3'f] [1,5]diazocine -6,7,14(8H)-trione (3 i), 1.2 equivalent of styrene 10 (14 mg), 5 mol% Pd(OAc) 2 (1.2 mg), 20 mol% PPh 3 (7 mg) and 2 equivalent of K 2 CO 3 ( 30 mg) in 1 mL of DMF:H 2 O (1 : 1) was purged with argon gas and stirred at 100°C temperature on a preheated oil bath for 12hr. After completion of the reaction (monitored by TLC), the resulting mixture was cooled to room temperature and extracted with EtOAc (2 × 10 mL).…”

Heck Macrocyclization in Forging Non-Natural Large Rings including Macrocyclic Drugs

“…These rigidifying elements make their synthesis a nontrivial task, particularly in view of their close resemblance to synthetically more demanding medium-sized (8-to 11membered) rings compared with larger (≥15 membered) macrocycles [59]. Intramolecular Heck arylation [6,60], as testified through the successful assembly of numerous 5-and 6-membered rings [61][62][63][64][65][66][67][68][69][70][71], turned out to be indispensable to access macrocyclic (R)-42, 44, 46, and 40 during the initial drug discovery campaign (Figure 7A) [55]. Subsequently, this synthetic approach was implemented to produce radiolabeled isotopologues for positron emission tomography (PET) imaging [72].…”

A Compilation of Synthetic Strategies to Access the Most Utilized Indoloquinoline Motifs

“…A similar strategy was re-visited by Mohanakrishnan and colleagues. [54] The reaction started with the same starting material (107). However, the cyclization step was performed via palladium-catalyzed Heck-type reaction to form the quinoline rings.…”

“…This work thus demonstrated a rather lengthy (five steps) synthetic access to 7 H ‐indolo[2,3‐ c ]quinoline 3 to only a few successful cases (pathway A, Scheme 22). A similar strategy was re‐visited by Mohanakrishnan and colleagues [54] . The reaction started with the same starting material ( 107 ).…”