Isoxazolinoisoquinoline Heterocycles via Solid-Phase Reissert and Suzuki Reactions

Abstract

A traceless solid-phase synthesis strategy has been developed that delivers novel isoxazolinoisoquinoline heterocycles. The process consists of solid-phase Reissert formation (isoquinoline f I), Suzuki coupling lithiation, and subsequent C1-alkylation (I f II), and exo-olefin selective 1,3dipolar nitrile oxide cycloaddition followed by Reissert hydrolysis (II f III) to liberate the targeted heterocycle.

The Suzuki Reaction with Arylboron Compounds in Arene Chemistry

“…The process consists of three steps: (a) Solid-phase Reissert formation by the reaction of polymer-supported benzoic acid chloride resin with an isoquinoline, followed by reaction with TMSCN to afford the aryl bromide of Reissert 30, (b) Suzuki coupling of the solid-phase Reissert 30 with phenylboronic acid to provide the coupling product, and (c) subsequent treatment of the coupling product with aqueous KOH to produce 31 (86 % overall yield based on the starting bromide) (Eq. (62)) [99].…”

CC Bond‐Forming Reactions

“…The Pd-aryl or -alkenyl complex bearing an X" group then reacts with the incoming alkene initially by co-ordination to its p system (17). In a subsequent rearrangement, the aryl functionality, stemming from the aryl or alkenyl halide, adds onto the alkene (18). The presence of water or Cl -was found beneficial in this step.…”

“…Et 3 N (200 mL, 1.43 mmol) was added, followed by the dropwise addition of phenoxyacetyl chloride (100 mL, 0.72 mmol). The resin was agitated for 30 min at 0°C, allowed to warm to r. t. and shaken for 18 …”

“…Monoalkylation of an amino acid on a polymeric support using Schwesinger base (Table 8, entries 18,19) [472,473]: (This reaction is also suitable for alkylating amino acids bearing an a-alkyl substituent so as to give a dialkylated product. Here, the amino function has to be protected as an aldimine.…”

One-pot rapid and efficient synthesis of new spiro derivatives of 11H-indeno[1,2-b]quinoxalin-11-one, 6H-indeno[1,2-b]pyrido[3,2-e]pyrazin-6-one and isatin-based 2-pyrazolines

“…); thus, only a limited number of strategies have been successfully applied in the synthesis of heterocyclic scaffolds. [4][5][6][7][8][9][10] The development of new, rapid, and clean synthetic routes toward focused libraries of such compounds is therefore of great importance to both medicinal and synthetic chemists. [11][12][13][14] Consequently, the design Indenoquinoxaline derivatives are important classes of nitrogen containing heterocycles and they constitute useful intermediates in organic synthesis.…”