Tandem Addition/Cyclization for Access to Isoquinolines and Isoquinolones via Catalytic Carbopalladation of Nitriles

Abstract

The first example of the palladium-catalyzed sequential nucleophilic addition followed by an intramolecular cyclization of functionalized nitriles with arylboronic acids has been achieved, providing an efficient synthetic pathway to access structurally diverse isoquinolines and isoquinolones. This methodology has also been successfully applied to the total synthesis of the topoisomerase I inhibitor CWJ-a-5 (free base).

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…This procedure was applied to the synthesis of a topoisomerase I inhibitor (CW-j-a-5). 130 A different approach, which can be considered pseudo-domino process, was employed as key step in the asymmetric synthesis of (-)-α-lycorane, (-)zephyranthine, and a formal total synthesis of (+)clivonine. 131 Using a different approach, the synthesis of [3.3.1]-bicyclic system of Lycopodium alkaloids was achieved by a complex domino palladium-mediated oxidative dehydrogenation/hetero-Michael.…”

Divergent Palladium‐Catalyzed Tandem Reaction of Cyanomethyl Benzoates with Arylboronic Acids: Synthesis of Oxazoles and Isocoumarins

“…Nitriles are an important class of molecular building blocks in organic synthesis. [2] Significant progress toward understanding the carbopalladation of nitriles [3] has promoted the development of transition-metal-catalyzed transformations of various nitrile-containing functional groups by our group [4] and others [5] (Scheme 1a). The scope of this chemistry has been successfully extended to sodium aryl sulfinates or arylsulfinic acids, [6] aryl halides, [7] benzoic acids, [8] and arylhydrazines [9] as coupling partners in the last decade.…”

“…The scope of this chemistry has been successfully extended to sodium aryl sulfinates or arylsulfinic acids, [6] aryl halides, [7] benzoic acids, [8] and arylhydrazines [9] as coupling partners in the last decade. Inspired by our recent studies on palladium-catalyzed tandem reactions of o-cyanobiaryls with arylboronic acids for the synthesis of seven-membered 5H-dibenzo[c,e]azepines (Scheme 1b), [10] we envisaged that the palladiumcatalyzed addition of arylboronic acids to cyanomethyl 2-halogenated benzoates and sequential intramolecular Buchwald-Hartwig coupling cyclization would offer a new strategy for the synthesis of 2-arylbenzo[e] [1,4] oxazepin-5-ones (Scheme 1c, proposed transforma-tion). To our surprise, substitution at the 2-position of cyanomethyl benzoates was found to be crucial for the selective synthesis of five-membered oxazoles [11] and six-membered isocoumarins [12] (Scheme 1c, observed transformation).…”

Two‐Step One‐Pot Synthesis of Unsymmetrical (Hetero)Aryl 1,2‐Diketones by Addition‐Oxygenation of Potassium Aryltrifluoroborates to (Hetero)Arylacetonitriles

“…By pursuing these challenges, we envisioned that cost‐effective and commercially available phenylacetonitrile, in which a phenyl ring is attached at the α‐position to the cyano group, may serve as an ideal starting material for the synthesis of 1,2‐diketones. In recent years, nitriles and their derivatives have been extensively used for the synthesis of diverse heterocyclic compounds, as they are inexpensive, stable, nontoxic, and abundant in nature (Scheme a–c) . Nitriles may also serve as useful building blocks in organic synthesis.…”