Unexpected Cleavage of 2-Azido-2-(hydroxymethyl)oxetanes: Conformation Determines Reaction Pathway?

Abstract

An unanticipated cleavage of 2-azido-2-(hydroxymethyl)oxetanes is reported. In attempts to oxidize the title oxetanyl alcohols to the corresponding carboxylic acids with RuO4, cleaved nitriles were formed as the sole isolable products, while a closely related tetrahydrofuran gave solely the expected carboxylic acid. Quantum chemical calculations suggest that the divergent outcomes are governed by conformational differences in the azidoalcohols.

Ruthenium Tetroxide and Perruthenate Chemistry. Recent Advances and Related Transformations Mediated by Other Transition Metal Oxo-species

“…2-Azido-2-(hydroxymethyl)oxetanes 62 were transformed into acyclic nitriles 63 with loss of the alcohol carbon (Scheme 41) by reaction with RuCl 3 (cat. )/NaIO 4 under classical conditions [145]. The process proceeds with low yields but is interesting from a mechanistic point of view.…”

Pt-Catalyzed Rearrangement of Oxaspirohexanes to 3-Methylenetetrahydrofurans: Scope and Mechanism

“…3-Methylene-4-(2-phenyl­ethyl)­oxetan-2-one (1.88 g, 10 mmol) and 10% Pd on carbon (0.30 mmol, 0.32 g) were mixed in dry THF (10 mL) under a N 2 atmosphere. The reaction vessel was purged with H 2 for 10 min.…”

Recent Applications of Oxetanes in the Synthesis of Heterocyclic Compounds

“…These two oxetane-containing systems demonstrated analogous reactivity in the generation of oxetane oxocarbenium ions when treated with suitable Lewis acids or electrophiles (Scheme ). These oxocarbenium ions could be intercepted with nucleophiles, and the reaction outcome can be diverted to two distinct pathways, ring opening or 1,2-addition. ,− While there have been several functionalization strategies for oxetanes, , specifically at the C-3 position, in this section we report our work on the generation of oxetane oxocarbenium ions and their reactivity with nucleophiles via 1,2-addition. This constitutes an attractive method for C-2 functionalization of oxetanes.…”

“…In these reactions, aluminum served as a Lewis acid, generating the oxocarbenium ion; subsequent reaction with hydride or a methyl group provided 2-hydroxymethyloxetanes. Recognizing that this protocol offered a way to functionalize oxetanes at the C-2 position, the methodology was expanded to heteroatom nucleophiles, specifically azide and N -heteroaromatic bases. , The C-2 functionalization of oxetanes with N -heteroaromatic bases appears to be correlated with the p K a of the nucleophile, with more acidic nucleophiles (p K a < 10) favoring 1,2-addition while more basic nucleophiles provided mainly ring-opened products.…”