Synthesis of 3,4-dihydroisoquinoline N-oxides via palladium-catalyzed intramolecular cyclization of 2-alkylbenzaldoximes

Abstract

A novel process for the synthesis of 3,4-dihydroisoquinoline N-oxides via Pd(PPh3)4/PhCOOH-catalyzed intramolecular cyclization of 2-alkylbenzaldoximes was reported. The reaction of 2-alkylbenzaldoximes proceeded smoothly in the presence of 10 mol% Pd(PPh3)4 and 40 mol% PhCOOH in 1,4-dioxane at 100 o C to give the corresponding 3,4-dihydroisoquinoline N-oxides in good to high yields. A possible pathway for the production of 3,4-dihydroisoquinoline N-oxides via a π-allylpalladium complex was proposed. The present study provides a useful and new method for the formation of C-N bond in organic synthesis.

ortho-Halobenzyl Halides as Precursors for the Synthesis of Five- to Nine-Membered Ring Structures Employing Transition Metals as Catalysts

“…The current study exhibits a valuable and new protocol for the construction of C-N bond in the realm of organic synthesis. 75 Chen and colleagues successfully synthesized spiro[oxindole-3,5′-pyrrolo[2,1-a]isoquinolines] 194 in 2017 by reacting 2bromobenzyl bromides 1 and 3-pyrrolyl-2-oxiindoles 193 in DMF at 140 °C for 48 hours with Pd acting as a catalyst, PPh3 acting as a ligand, and sodium carbonate acting as a base (Scheme 68). A variety of spiro[oxindole-3,5′-pyrrolo[2,1a]isoquinolines] 194 were produced with yields as high as 92% using this approach.…”

Copper‐Catalyzed C(sp3)− Functionalization and Annulation of 2‐Bromoaryl Oximes with Active Methylene Compounds towards Synthesis of Isoquinoline N‐Oxides

“…On the other hand, the transition-metal catalyzed CÀ H activation is a productive and facile approach for the synthesis of N-heterocyclic compounds [7] and heterocyclic N-oxides. [8] The transition-metal catalyzed direct CÀ H functionalization and annulation of aryloximes for the synthesis of isoquinoline N-oxides surpasses the earlier traditional methods, and oxime was found as a facile precursor which can couple with alkynes, [9,10] diazo compounds, [11] and other coupling intermediates. [12] In 2013, Glorius group demonstrated the Rh(III)-catalyzed intermolecular annulation of aryloximes with diazo compounds to construct isoquinoline N-oxides (Scheme 1a).…”

“…However, over the past years, intermolecular cyclization for the synthesis of isoquinoline N-oxide has been described using expensive catalysts such as Rh, Ir, and Pd. [10] To extend the application of this strategy, our attention has been focused on the copper catalyst as it is capable towards the valence changing capacity to progress the redox reactions in either a singleelectron or a two-electron transfer approach, and used as a powerful, low-cost, easily available and biologically less toxic catalyst. Here, we report a copper(II)-catalyzed intramolecular cyclization of aryl oxime and active methylene compounds through CÀ H functionalization followed by the condensation process, to access isoquinoline N-oxides (Scheme 1).…”