Microwave-Assisted Palladium-Catalyzed Reductive Cyclization/Ring-Opening/Aromatization Cascade of Oxazolidines to Isoquinolines

Abstract

An efficient palladium-catalyzed reaction of N-propargyl oxazolidines for the construction of 4-substituted isoquinolines under microwave irradiation is developed. This transformation proceeds through a sequential palladium-catalyzed reductive cyclization/ring-opening/aromatization cascade via C–O and C–N bond cleavages of the oxazolidine ring. The practical value of this method has also been explored by conducting a millimole-scale reaction, as well as by transforming the isoquinoline into a key intermediate for the synthesis of a lamellarin analogue.

Diversely functionalized isoquinolines and their core-embedded heterocyclic frameworks: a privileged scaffold for medicinal chemistry

“…Xu et al developed a microwave-assisted synthesis of 4-substituted isoquinoline 16 (Scheme 2). 43 Palladium catalysed reductive cyclization of oxazolidine 14 affords the alkene intermediate 15 . Under acidic conditions, C–O and C–N bond cleaves in the oxazole ring, following the aromatization to afford isoquinoline derivative 16 .…”

“…Xu et al developed a microwave-assisted synthesis of 4-substituted isoquinoline 16 (Scheme 2). 43 Liu and co-workers reported a one-step domino approach towards the synthesis of imidazo[2,1-a]isoquinoline 26 (Scheme 4). 48 Sonogashira coupling between copper acetylide and bromophenyl benzimidazole 23 achieves the alkyne intermediate 25.…”

“…Suzuki coupling between vinyl boronate ester 10 and 2-halobenzonitriles 9 leads to a vinyl ether adduct 11 that generates an amide-aldehyde intermediate 12 on hydrolysis. Compound 12 then switches to cascade cyclization followed by dehydration affording isoquinolone 13.Xu et al developed a microwave-assisted synthesis of 4-substituted isoquinoline 16 (Scheme 2) 43. Palladium catalysed reductive cyclization of oxazolidine 14 affords the alkene intermediate 15.…”

Synthesis ofN-alkenylisoquinolinonesviapalladium-catalyzed cyclization/C4–O bond cleavage of oxazolidines

“…14 Very recently, our group reported the Pd-catalyzed reductive annulation/C 2 –O and C 5 –N bond cleavage of oxazolidines to access a range of isoquinolines, which are unreachable via conventional methods (Scheme 1B, reaction (a)). 15 Despite these achievements, chemoselective control of the C 4 –O bond activation of the oxazolidine ring remains elusive. To the best of our knowledge, this is the first work that describes an efficient approach for the chemoselective synthesis of cyclic enamides via the palladium-catalyzed cyclization and C 4 –O bond cleavage of oxazolidines (Scheme 1B, reaction (b)).…”

Pd-Catalyzed Ring Restructuring of Oxazolidines with Alkenes Leading to Fused Polycyclic Indolizines

“…However, to the best of our knowledge, the participation of oxazolidines in a 1,3-dipolar cycloaddition/cycloreversion process has not been described before. Inspired by these works and our previous study, we designed a novel strategy for constructing fused polycyclic indolizines from alkenes and N -propargyl oxazolidines, which are readily generated via A 3 -type coupling (Scheme c). This whole transformation might proceed through a sequential Pd-catalyzed 6- exo -dig cyclization/proton transfer/[3+2] cycloaddition/cycloreversion [involving both C­(sp 3 )–C­(sp 3 ) and C–O bond cleavage of the oxazolidine ring]/aromatization process.…”