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

Abstract

The Ley-Griffith tetra-n-propylammonium perruthenate (TPAP) catalyst has been widely deployed by the synthesis community, mainly for the oxidation of alcohols to aldehydes and ketones, but also for a variety of other synthetic transformations (e.g. diol cleavage, isomerizations, imine formation and heterocyclic synthesis). Such popularity has been forged on broad reaction scope, functional group tolerance, mild conditions, and commercial catalyst supply. However, the mild instability of TPAP creates preparation, storage, and reaction reproducibility issues, due to unpreventable slow decomposition. In search of attributes conducive to catalyst longevity an extensive range of novel perruthenate salts were prepared. Subsequent evaluation unearthed a set of readily synthesized, bench stable, phosphonium perruthenates (ATP3 and MTP3) that mirror the reactivity of TPAP, but avoid storage decomposition issues.

Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations

“…[36] Notably,t he transformation was greatly accelerated by the addition of aL ewis acid (BCl 3 ). [36c] Given that the valence isomerizationc an be performed without ar hodium catalyst and best proceeds with an electron deficient moiety appended directly to the cubane framework, an opportunity to incorporate both preceptsi nto one contiguous methodology was envisaged.O ur recent work extending the Ley-Griffith oxidation [37] [that is, tetrapropylammonium perruthenate (TPAP) oxidation] [38] in the context of tandemW ittig reactions [39] was applied to cubane-alcohols 50 (see the Supporting Information for synthetic methods) to expand the mono-a nd 1,2-disubstituted COT derivativel ibrary. Ar ange of mono-and 1,4-disubstituted COT derivatives were obtained (i.e., 55-65)i ny ields ranging from 15-57 %, which, considering three reactions are occurring in the one pot, was deemed satisfactory (Scheme 6).…”

Ranking Oxidant Sensitiveness: A Guide for Synthetic Utility

“…[10] The popularity of these systems is due to the mild conditions requiredt op romote oxidation, provenw ide functional groupt olerance, [11] and limited toxicity.H owever,i nt he case of IBX it has been knownt oe xplode, [12] and although as tabilized version (SIBX, 5)i sa vailable, [13] othero xidants also fall into the category of being impact and/or thermally sensitive.F or example, organic peroxides [14] [e.g., meta-chloroperoxybenzoic acid (mCPBA) (6)] [15] and the nitroxyl radicalA NBO. [16] In addition,i n the course of developing perruthenates ATP3 (7)a nd MTP3 (8), [17] whicha re much more bench stable compared to TPAP, we discovered that they were impact sensitive. This aspect provided substantial inspiration to investigate and rank the sensitiveness of ar ange of common oxidants used in both academic and industrial settings.…”

“…Analysis using sealed cell differential scanning calorimetry (scDSC) facilitated Yoshida correlations, which were compared to impact sensitiveness and electrostatic discharge experiments (ESD),t hat enabled sensitiveness ranking. Methyltriphenylphoshoniump erruthenate (MTP3, 8), isoamyltriphenylphosphonium perruthenate (ATP3, 7)a nd tetraphenylphosphonium perruthenate (TP3,9)w ere found to be the mosts ensitive followed by 2-iodoxybenzoic acid (IBX, 2)a nd benzoylp eroxide (BPO, 10), whereas the most benign were observed to be Oxone (12), manganese dioxide (MnO 2 ,13), and N-bromosuccinimide (NBS,17).…”

“…Of these oxidants, only SO 3 ·pyr did not flag in the Yoshida correlations,s uggesting as lightly better safety profile than the others. Finally,w ith no ignitions at 4.5 Jw ere mCPBA (6), CAN (11), oxone (12), MnO 2 (13), NBS (17), and TPAP (4).…”

Synthetic Tigliane Intermediates Engage Thiols to Induce Potent Cell Line Selective Anti‐Cancer Activity

“…With 22 and 23 in hand as electiveo xidation strategy was pursued. Bis trimethylsilyl protection afforded 24 in high yield (85 %), which under controlled conditions was mono-deprotected at C5 using citric acid, andthe mono-ol was then immediately oxidized via aL ey-Griffith oxidation (TPAP [38] )t og ive ketone 25 (Scheme 3). Rubottom oxidation [39] of 25 gave the hydroxy-ketone 26 in 61 %y ield, along with the intermediate epoxide ( 27)t hat could be converted into 26 on treatment with mild acid.…”