Buchwald–Hartwig Reactions of Monohaloflavones

Abstract

Thiol–ene “click” chemistry has emerged as a powerful strategy to construct carbon–heteroatom (CS) bonds, which generally results in the formation of two regioisomers. To this end, the neutral ionic liquid [hmim]Br has been explored as a solvent cum catalyst for the synthesis of linear thioethers from activated and inactivated styrene derivatives or secondary benzyl alcohols and thiols without the requirement of using a metal complex, base, or free radical initiator. Furthermore, detailed mechanistic investigations using 1H NMR spectroscopy and quadrupole time‐of‐flight electrospray ionization mass spectrometry (Q‐TOF ESI‐MS) revealed that the “ambiphilic” character of the ionic liquid promotes the nucleophilic addition of thiol to styrene through an anti‐Markovnikov pathway. The catalyst recyclability and the extension of the methodology for thiol–yne click chemistry are additional benefits. A competitive study among thiophenol, styrene, and phenyl acetylene revealed that the rate of reaction is in the order of thiol–yne>thiol–ene>dimerization of thiol in [hmim]Br.

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer’s Agents: Design, Synthesis and Biological Evaluation

“…The synthon 8 and the 1,ω-diaminotacrines 9 – 15 were utilized for formation of the desired 6-Cl-THA-scutellarin hybrids K1383 – K1389 in a Buchwald-Hartwig cross-coupling reaction under catalysis of Pd 2 (dba) 3 + BINAP + NaOtBu in dry toluene [ 47 ]. The final compounds were obtained as yellow powders in yields ranging from 15–88%.…”

“…To the appropriate N -(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)alkane-1-ω-diamine 9 – 15 (0.3 mmol) dissolved in dry toluene under an inert atmosphere compound 7 (0.26 mmol), palladium complex (0.002 mmol), consisting of Pd 2 (dba) 3 (tri(dibenzylideneacetone)dipalladium (0)), BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) and NaO t -Bu, were added [ 47 ]. The reaction mixture was held at 110 °C for 24 h. The solvent was evaporated under the reduced pressure and the residue purified by column chromatography using chloroform:methanol (50:1) as a mobile phase.…”

One-pot aminobenzylation of aldehydes with toluenes

“…To further demonstrate the synthetic potential of the aminobenzylation, the product derived from 2 - bromotoluene, NaN(SiMe 3 ) 2 , and benzaldehydes 1a , 1n , 1q , and 1v were readily converted into valuable 2-aryl-substituted indoline derivatives using a Buchwald–Hartwig amination in 81–90% yield (Fig. 4c ) 50 . N -Substituted 2-arylindoline derivatives are used to treat estrogen-deficiency diseases 51 .…”

The rearrangement of tosylated flavones to 1′-(alkylamino)aurones with primary amines

“…Note that no signals for C2 were observed in the 13 C{ 1 H} NMR spectra of 3a-i, probably due to overlaps with other signals. The free rotation of the C2-C10 bond in the last step of the reaction mechanism, as proposed by Kónya et al, 35 allows formation of E and Z isomers. The transformation into the thione increases the rotational freedom and the E isomer is exclusively obtained in the case of 4a.…”

“…However, recently Patonay et al identified the ring contraction to the aurone structure based on 2D NMR spectroscopy through comparison with a synthesized 3-aminoflavone. 35 In the molecular structure of 3a, an intramolecular hydrogen bond between the amine functionality and the carbonyl of the benzofuranone moiety is evident, yielding a thermodynamically stable 6-membered ring. The bond length C2-C10 is significantly shorter in 3a (1.372(3) Å) than in 4a (1.403(2) Å) and indicates the presence of an exocyclic double bond in 3a.…”