Regioselective Functionalization of Ester-, Amide-, Carbonate-, and Carbamate-Substituted 2-Phenyl-2-oxazolines with Mixed Lithium–Magnesium Amides

Abstract

We have prepared novel highly functionalized benzene derivatives by regioselective metalation of ester-, amide-, carbamate-, and carbonate-substituted 2-phenyl-2-oxazolines with mixed lithium−magnesium amides followed by reaction with different electrophiles. While a complementary metalation site can be accessed by using different bases, steric and electronic effects promoted by the aromatic ring substituents also play an important role in reaction regioselectivity. Computational calculations of the aromatic hydrogen pK a values have helped us to rationalize the metalation preference by the complex-induced proximity effect concept.

Substitution Effect on 2-(Oxazolinyl)-phenols and 1,2,5-Chalcogenadiazole-Annulated Derivatives: Emission-Color-Tunable, Minimalistic Excited-State Intramolecular Proton Transfer (ESIPT)-Based Luminophores

“…[2M + Na] + calcd for [C 26 H 30 N 2 NaO 6 + ]: 489.1996; Found: 489.1994. The analytical data are in accordance with the literature …”

Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

“…With 10g in hands, we studied its magnesiation with TMPMgCl·LiCl . Interestingly, despite the powerful metalation directing effect of the 2-oxazoline group, − metalation exclusively occurred at the C8 ring position to yield the iodide 10h in 50% through iodine quenching. Similarly, application of the in situ -trapping metalation strategy through addition of TMPMgCl·LiCl to 10g in the presence of ZnCl 2 (0.5 equiv) led to the full conversion of the starting material within 1 h at room temperature.…”

The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update

“…Furthermore, KEM necessitates proton transfer as the only step between the reactant and the lithiated product. Qualitatively, experimental observations ,,, based on geometrical consideration of a coordinated DMG-base species proximate to the reactive site are suggestive of the significance of the CIPE supposition. Furthermore, kinetic analyses on the ortho -lithiation of anisole and ArOAms provide evidence for mixed dimers − or triple ions ,, as plausible intermediates for the exhibited first-order kinetics of the reactions.…”