A [4 + 2] Cycloaddition Strategy to Pyridine Boronic Ester Derivatives

Abstract

Alkynylboronate cycloadditions of 1,4-oxazin-2-ones and 2-pyrazinones provide a direct and regioselective route to functionalized pyridine boronic ester derivatives.

Domino Reaction Sequence for the Synthesis of [2.2.2]Diazabicycloalkenes and Base-Promoted Cycloreversion to 2-Pyridone Alkaloids

“…7 In comparison, merged cycloaddition/cycloreversion approaches for the direct synthesis of 2-pyridones are not common; 8 however, Hoornaert and co-workers validated the possibility of this approach using cycloaddition of chlorinated pyrazinone intermediates. 9 The cycloreversion of the intermediate [2.2.2]diazabicycloadducts derived from these chlorinated pyrazinone precursors has two primary limitations: (1) extrusion of cyanide or cyanate derivatives requires high temperatures 10 (at or above 140 °C), and (2) extrusion is often nonselective and gives mixtures of both pyridine and pyridone products. 9 …”

α-Hydroxyacids accelerate the Diels–Alder reaction of dibutyl vinylboronate with cyclopentadiene: experimental results and mechanistic insights

“…Based on previous results from our group, we first investigated the use of microwave heating. 6 A slightly higher yield (47%) was obtained in 1 h at 70 °C with 2 equivalents of 5. We then screened the solvent, the temperature, the addition of an alcohol, 20 and the number of equivalents of 5 (Scheme 2).…”

“…Fortunately, (S)mandelic acid (5) afforded a 36% yield. Next, we evaluated the use of (S)-O-acetylmandelic acid (6) and (S)-methyl mandelate (7). Since both compounds gave much lower yields than 5 (<10%), we demonstrated that both functional groups of the αhydroxyacid are necessary.…”

Application of 1,4-Oxazinone Precursors to the Construction of Pyridine Derivatives by Tandem Intermolecular Cycloaddition/Cycloreversion

“…Recent computational efforts suggest that oxazinones are the most reactive precursors for the [4 + 2] reaction component (of the tandem cycloaddition/cycloreversion sequence) and proceed readily with either electron-rich or electron-deficient substrates to yield pyridine products after loss of carbon dioxide . Because of the increased reactivity, 1,4-oxazinones are attractive substrates that can enable the use of less reactive 2π cycloaddition reaction components and/or permit use of milder reaction conditions . In this way, ubiquitous alkyne precursors may be used routinely and at reaction temperatures that are operationally convenient for the practicing chemist.…”