2,2-Bifunctionalization of Norbornene in Palladium-Catalyzed Domino Annulation

Abstract

A palladium-catalyzed three-component [2 + 3 + 1] domino annulation among 3-iodochromones, αbromoacetophenones, and norbornene is presented, affording various chromone-containing polycyclic compounds bearing fused/spiro/bridged-ring systems. For the first time, the 2,2bifunctionalization of norbornene was realized in palladiumcatalyzed domino reaction. This cyclization characterizes three new bonds (two C−C and one C−O) in a single operation and produces nontrivial spiro-norbornane fragments in comparison with a traditional palladium-catalyzed process involving norbornene.

Efficient Assembly of Molecular Complexity Enabled by Palladium‐Catalyzed Heck Coupling/C(sp2)−H Activation/ C(sp3)−H Activation Cascade

“…In continuation of our investigations on the reactivity of bridged olefins [18,19] as well as our interests in the syntheses of various heterocycles, [21] we envisioned that a novel methodology without oxo-assisted anti-β-H elimination or acid-catalyzed intramolecular cyclization, in which three-component reaction among 3iodochromones (1), benzyl bromides (2), and NBE (3 a) led to another kind of [2 + 2 + 1] adducts (4) through a palladium-catalyzed Heck coupling/C (sp 2 )À H activation/C(sp 3 )À H activation cascade (Scheme 1C). We surmised that Pd(0) reacts with 3iodochromones (1) to generate Pd(II) intermediate A via oxidative addition, which generates the key fivemembered palladacycle C through migratory insertion of NBE (3 a) and subsequent ortho-CÀ H activation in the presence of base.…”

“…[17] Based on the important role of chromone scaffold in medicinal chemistry, we recently developed a novel palladium-catalyzed three-component [2 + 3 + 1] domino annulation among 3-iodochromones, α-bromoacetophenones, and NBE for building chromone-containing polycyclic compounds with NBE incorporated, in which the 2,2-bifunctionalization of NBE was first realized (Scheme 1A). [18] Moreover, we further developed a palladium-catalyzed [2 + 2 + 1] domino annulation of 3-iodochromones, α-bromoacetophenones, and tetracyclododecene (TCD) involving a 6,7-bifunctionalization of TCD, affording another kind of polycyclic compounds (Scheme 1B). [19] The former process involving oxo-assisted anti-β-H elimination (transition state I, TS I) and acid-catalyzed intramolecular cyclization (TS II) with the hydroxyl as nucleophile gave the [2 + 3 + 1] adducts, while the later one occurred via oxo-assisted anti-β-H elimination (TS III) and acid-catalyzed intramolecular cyclization (TS V) with the α-carbon of the carbonyl as nucleophile afforded the [2 + 2 + 1] adducts.…”

Six-membered ring systems: with O and/or S atoms

“…Double annulation reactions of benzamides without o-substitution with unactivated alkynes mediated by ruthenium(II) (19JOC13033) or rhodium(III) (19JOC15697) catalysts provide a wide variety of isoquinoline-fused pyrans (Scheme 2). Palladium(II)-catalyzed three-component [2 þ 3 þ 1] domino annulation of 3-iodochromones with a-bromoacetophenones and norbornene leads to spironorbornene chromen-4-ono[3,2-c]pyrans in moderate to good yields and with high diastereoselectivity (Scheme 3) (19OL8857).…”

Transition metal-catalyzed coupling of heterocyclic alkenesviaC–H functionalization: recent trends and applications

“…Recently, a rare example of three-component [2 + 3 + 1]-annulation of 3-iodochromones, α-bromoacetophenones and nor- bornenes has been found to be successful (Scheme 133). 195 In search of ligands, electron-deficient ligands produced the best results and chromone-fused polycycles showed good diastereoselectivity.…”