Nonstabilised Azomethine Ylids from N-Oxides: Unravelling the Deprotonation of N-Methylmorpholine N-Oxide

Abstract

Nonstabilised azomethine ylids (NAYs) are useful 1,3-dipoles, but their synthetic applications are restricted by the high temperatures often needed for their generation, and by an incomplete understanding of the effect of heteroatoms in cyclic systems. We have examined the behaviour of N-methylmorpholine N-oxide (NMO) as a NAY precursor in the Roussi reaction (low-temperature reaction of an N-oxide with strong base). The choice of base is critical to achieving cycloadduct formation. We report synthetic and computational (density functional theory) investigations of the products obtained with different bases and their mechanisms of formation.

Multi-Ion Bridged Pathway of N-Oxides to 1,3-Dipole Dilithium Oxide Complexes

“…However, with a suggested mechanism involving an electrophilic iminium intermediate, many synthetic chemists have avoided the reaction since such intermediates lack the control to produce high yields within complex systems. Yet, neither Roussi nor other recent workers considered the formation of a multi-ion bridged intermediate, which we show is favored over the iminium intermediate. By moving through the multi-ion bridged intermediate, no electrophilic intermediate exists within the reaction path, considerably broadening the scope of compatible substrates.…”

“…Similarly, a recent paper sought to further understand the mechanism of 1,3-dipole synthesis from N -methylmorpholine N -oxide (NMO) . However, with an oxygen contained in the ring system, NMO provided a challenging substrate, resulting in a variety of undesired side products . To avoid unnecessary complexity, we removed excess reactive functionality from our model systems and chose to investigate tertiary alkylamine N -oxides.…”

“…64 Similarly, a recent paper sought to further understand the mechanism of 1,3-dipole synthesis from N-methylmorpholine N-oxide (NMO). 68 However, with an oxygen contained in the ring system, NMO provided a challenging substrate, resulting in a variety of undesired side products. 68 To avoid unnecessary…”

Selectivity Modulation of the Ley–Griffith TPAP Oxidation with N‐Oxide Salts

“…Adding to this situation is: (1) the hygroscopic nature of the traditional co‐oxidant NMO ( 4 ), which has somewhat been addressed by application of a polymer‐bound version [PSNMO ( 6 )]; and (2) the reaction produces an equivalent of water after catalyst turnover, so molecular sieves (4 Å) are required. In the process of working with NMO ( 4 ), we recently discovered the non‐hygroscopic salt NMO · TPB ( 7 ) (Scheme ), which could be substituted for NMO in the Ley–Griffith oxidation of activated alcohols to activated aldehydes 8 . Importantly, the utility of 7 did not require anhydrous conditions .…”

Roger F. C. Brown Memorial Issue

“…[22,23] Craig Williams, Elizabeth Krenske and Paul Malek Mirzayans (UQ) detail a combined experimental and computational study of azomethine ylide formation from N-oxides. [24] Glen Deacon, David Turner and co-workers (Monash) use hightemperature (solid state) chemistry to achieve an unexpected formation of a biquinolinolate ligand from 8-quinoline and rareearth or transition metals, [25] and Andrew Abell et al (Adelaide) describe a preparation of macrocyclic calpain inhibitors. [26] Steven Langford (Monash) reports on crown ether derivatised pyromellitic diimides, [27] and David Black (UNSW, formerly of Monash) on the synthesis, structures, and conformations of bisglyoxylamides derived from bis-acylisatin.…”