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

Abstract

A wide variety of novel non‐hygroscopic N‐oxide tetraphenylborate salts were synthesized and evaluated as co‐oxidants in the Ley–Griffith (TPAP) oxidation of benzylic and allylic alcohols under non‐anhydrous conditions. The novel DABCOO·TPB (2:1) salt was herein unearthed as a viable competitor to the first‐generation NMO·TPB (2:1) salt, but more importantly gave increased performance under oxidative competition. X‐ray crystal structure analysis and NMR spectroscopy revealed that depending on the crystallization conditions 1:1, 2:1 or 3:2 N‐oxide–tetraphenylborate salts could be formed.

Influence of the position of the methyl substituent and N-oxide formation on the geometry and intermolecular interactions of 1-(phenoxyethyl)piperidin-4-ol derivatives

“…The differences are observed in the conformation of the linker, which in consequence changes the mutual orientation of both rings [interplanar angle = 34.05 7], as well as in the location of the hydroxy group on the piperidine ring. The formation of the N-oxide of the piperidine ring in other derivatives containing this moiety and their crystal structures have been reported previously (Jaskó lski, 1987;Jaskó lski et al, 1979Jaskó lski et al, , 1982aMoore et al, 2016;Peeters et al, 1996;Ravikumar et al, 2005). The N1-O3N bond length is 1.3994 (12) Å , which is similar to values in other crystal structures of piperidine N-oxide derivatives deposited in the CSD.…”

ATP3 and MTP3: Easily Prepared Stable Perruthenate Salts for Oxidation Applications in Synthesis

“…We discovered that TPAP will smoothly oxidize activated primary and secondary alcohols to aldehydes and ketones without the requirement for stringent anhydrous conditions, using the non‐hygroscopic salt NMO⋅TPB ( 10 , Scheme ) . Subsequently it was later observed that DABCOO⋅TPB ( 11 ) performed more efficiently as a co‐oxidant, demonstrating that chemoselective diol protection could be avoided . Furthermore, we found that TMEDAO 2 ( 12 ) is a more atom economical co‐oxidant that acts synergistically with stabilized ylides to facilitate Ley – Griffith–Wittig reactions; again without the requirement of anhydrous conditions (Scheme ).…”

“…[12] Subsequently it was later observed that DABCOO·TPB (11)p erformed more efficiently as ac o-oxidant, demonstrating that chemoselective diol protection could be avoided. [13] Furthermore, we found that TMEDAO 2 (12)i sa more atom economical co-oxidant that acts synergistically with stabilized ylides [14] to facilitate Ley-Griffith-Wittig reactions; [15] again without the requirement of anhydrous conditions (Scheme 1).…”

Elucidating the mechanism of the Ley–Griffith (TPAP) alcohol oxidation

“…Like many named reactions, modifications of the Ley–Griffith reaction have been reported 29 – 37 ( e.g. NMO·TPB 38 and DABCOO·TPB 39 from our own laboratory), as have numerous alternative applications using TPAP as a catalyst. 40 – 51 …”