Palladium-catalysed stereoselective synthesis of 4-(diarylmethylidene)-3,4-dihydroisoquinolin-1(2H)-ones: expedient access to 4-substituted isoquinolin-1(2H)-ones and isoquinolines

Abstract

An efficient method has been developed for the stereoselective synthesis of 4-(diarylmethylidene)-3,4-dihydroisoquinolin-1(2H)-ones 7 through tandem Heck-Suzuki coupling at rt using easily available substrates. DBU easily converted the exocyclic double bond of these compounds to endo, furnishing 8 and 9. Reduction of the carbonyl group of 7 was smoothly carried out with borane dimethyl sulphide. Subsequent treatment with KOBu provided an easy access to 4-substituted isoquinolines 10a if carried out in refluxing 1,4-dioxane, while reaction in DMF at rt led to the incorporation of an extra hydroxyl group at the benzylic position of the isoquinolines to give 10b. This straightforward and metal free procedure would serve as a better alternative to the prevalent procedures. Few of the products could also be transformed into heterocyclic scaffolds structurally resembling known bioactive compounds.

Stereoselective Domino Heck‐Suzuki Reactions

“…[21] Later, Chowdhury and coworkers applied and improved Grigg's protocol for getting access to the arylidene-substituted 3,4-dihydroisoquinolin-1(2H)-one skeleton. [34] For this purpose, a series of propargylic amides 65 were submitted to the domino reaction with various aromatic and heteroaromatic boronic acids in the presence of tripotassium phosphate. Thus 4-(diarylmethylene)-3,4-dihydroisoquinolin-1(2H)-ones 66 were obtained mostly in high yields and with a wide variation of the aryl and hetaryl residues at the tetra-substituted double bond.…”

Synthesis of dihydroisoquinolinone-4-methylboronic esters via domino Heck/borylation using a structurally characterized palladacycle as a catalyst

“… 1 They have widespread applications as drugs in various therapies including cancer treatment. 2 Owing to the importance of the dihydroisoquinolinone motif there has been a plethora of synthetic methodologies reported in the literature, which have been reviewed in detail recently. 3 Most of these methods do not directly lead to the synthesis of targeted drug, necessitating the building of the remaining parts of the drug.…”

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

“…Intramolecular palladium-catalyzed versions are particularly attractive, since they afford polycarbo-and heterocyclic systems via sequential reactions of the vinylpalladium intermediate [20][21][22][23][24][25]. In this field, a variety of regio-and stereoselective Pd-catalyzed cascade reactions, consisting of the addition of in situ-generated arylpalladium complexes over a proximate carbon-carbon triple bond, followed by cross-coupling reactions, have been reported [26][27][28][29][30][31].…”