New Oxidative Transformations of Phenolic and Indolic Oxazolines:  An Avenue to Useful Azaspirocyclic Building Blocks

Abstract

The oxidative cyclization of a phenolic amide to a spirolactam has long been regarded as an "impossible" reaction, because exposure of the substrates to a variety of oxidants results in formation of spirolactones with consequent loss of the amine segment. We recently communicated that this heretofore unknown transformation may be achieved by oxidation of oxazoline analogues of phenolic and indolic amides. Herein, we provide full details of our work.

Oxidative Dearomatization of Phenols: Why, How and What For?

“…47 It was particularly important to verify this structural connectivity, as the nucleophilic reactivity of an amide oxygen is known to compete with that of the nitrogen atom. 49,50 Going by the structures of the products we could identify from our reaction mixtures, this competition apparently did not occur to any significant extent.…”

The Chemical Synthesis of Tetrodoxin: An Ongoing Quest

“…In all cases, “N” emerges from the reaction as part of an amide functionality; hence the terminology “oxidative amidation of phenols”. Three modes of oxidative amidation are currently known, depending on whether N is part of an oxazoline (intramolecular) [71–73], a sulfonamide or a phosphoramide (intramolecular) [74–76], or a nitrile (bimolecular) [77,78]. The reaction is most often carried out with para -substituted phenols, as dictated by the structure of various synthetic targets [79–81], but ortho -oxidative amidation is perfectly possible [70,75,82].…”

Oxidative Spirocyclization of Phenolic Sulfonamides: Scope and Applications

“…[3] Intramolecular and bimolecular variants of the reaction are known. In the intramolecular regime, an oxazoline [4] or sulfonamide [5] serve to intercept 2. [6] In the bimolecular mode, acetonitrile discharges this function.…”