Synthesis of substituted 3,4-dihydroquinazolinones <i>via</i> a metal free Leuckart–Wallach type reaction

Bokale-Shivale, Suvarna; Amin, Mohammad Al; Sawant, Rajiv T.; Stevens, Marc Y.; Turanli, Lewend; Hallberg, Adam; Waghmode, Suresh B.; Odell, Luke R.

doi:10.1039/d0ra10142g

Cited by 7 publications

(5 citation statements)

References 43 publications

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Section: Miscellaneous Transformations With Deuterium Incorporationmentioning

confidence: 99%

“…Selective deuterium incorporation at the 4-position of a quinazolinone scaffold, which is of interest in medicinal chemistry, was achieved by Odell and co-workers via a Leuckart-Wallach type reaction. 356 In their metal-free procedure, deuterated formic acid plays the role of solvent, reductant, and isotope source (Scheme 135). Amine condensation on the more reactive aldehyde function forms an imine that subsequently cyclizes on the carbamate moiety leading to an acyl iminium ion.…”

Section: Further Approachesmentioning

confidence: 99%

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Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017−2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

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Section: Miscellaneous Transformations With Deuterium Incorporationmentioning

confidence: 99%

Section: Further Approachesmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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“…Condensation of amine 15 and aldehyde in 13 generates imine I . The imine then adds to the carbamate group, releasing methanol and forming N -acyliminium II . , Electrophile II then undergoes alkynyl Prins cyclization to form the final quinazolinone product 16 .…”

Section: Resultsmentioning

confidence: 99%

“…The imine then adds to the carbamate group, releasing methanol and forming N-acyliminium II. 20,21 Electrophile II then undergoes alkynyl Prins cyclization to form the final quinazolinone product 16. Finally, we tested cyclization onto the N-acyliminium ion intermediate generated from succinimide-derived reactant 17r.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Alkynyl Halo-Aza-Prins Annulative Couplings

Hernandez,

Lawrie,

Frontier

2023

J. Org. Chem.

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This article is a comprehensive report describing our studies in the field of aza-alkynyl Prins chemistry, comparing and contrasting the different reaction partners and reactivities observed during method development. The synthetic strategies combine an alkynyl aza-Prins coupling with an annulation, enabling the preparation of different nitrogen-containing heterocycles. Different iminium ions are explored as viable electrophiles for an alkynyl Prins cyclization, terminated by capture with a halogen nucleophile to form a vinyl halide. The synthetic utility of this functional handle is exploited through a number of Suzuki cross-couplings, allowing for the preparation of a modest library of compounds. In most cases, the Prins couplings are highly selective for the vinyl halides with E geometry, resulting from anti-addition across the alkyne.

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Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope

et al. 2022

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Herein we disclose a mild protocol for the reductive functionalisation of quinolinium and isoquinolinium salts. The reaction proceeds under transition‐metal‐free conditions as well as under rhodium catalysis with very low catalyst loadings (0.01 mol %) and uses inexpensive formic acid as the terminal reductant. A wide range of electrophiles, including enones, imides, unsaturated esters and sulfones, β‐nitro styrenes and aldehydes are intercepted by the in situ formed enamine species forming a large variety of substituted tetrahydro(iso)quinolines. Electrophiles are incorporated at the C‐3 and C‐4 position for quinolines and isoquinolines respectively, providing access to substitution patterns which are not favoured in electrophilic or nucleophilic aromatic substitution. Finally, this reactivity was exploited to facilitate three types of annulation reactions, giving rise to complex polycyclic products of a formal [3+3] or [4+2] cycloaddition.

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Synthesis of substituted 3,4-dihydroquinazolinones via a metal free Leuckart–Wallach type reaction

Abstract: A novel cascade cyclization/Leuckart–Wallach type strategy to prepare biologically important 3,4-dihydroquinazolinones is presented.

Cited by 7 publications

References 43 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Alkynyl Halo-Aza-Prins Annulative Couplings

Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope

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