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Tandem oxidative-dehydrogenation of primary alcohols to give α,β-unsaturated aldehydes in one pot are rare transformations in organic synthesis, with only two methods currently available. Reported herein is a novel method using the bench-stable salt methyltriphenylphosphonium perruthenate (MTP3), and a new co-oxidant NEMO·PF6 (NEMO = N -ethyl- N -hydroxymorpholinium) which provides unsaturated aldehydes in low to moderate yields. The Ley-Griffith oxidation of (hetero)arylated primary alcohols with N -oxide co-oxidants NMO (NMO = N -methylmorpholine N -oxide)/NEMO, is expanded by addition of the N -oxide salt NEMO·PF6 to convert the intermediate saturated aldehyde into its unsaturated counterpart. The discovery, method development, reaction scope, and associated challenges of this method are highlighted. The conceptual value of late-stage dehydrogenation in natural product synthesis is demonstrated via the synthesis of a polyene scaffold related to auxarconjugatin B. A novel method is described, using perruthenate salts, for performing the rarely reported dehydrogenation of primary alcohols to afford unsaturated aldehydes in low to moderate yields. The discovery, method development, reaction scope, and associated challenges of this method are presented in detail. [ABSTRACT FROM AUTHOR]

The Ley–Griffith oxidation, which is catalyzed by tetra‐n‐propylammonium perruthenate (TPAP, nPr4N[RuO4]), is a popular method for not only controlled oxidation of primary alcohols to aldehydes, but also a host of other synthetically useful transformations. While the fundamental reaction mechanism has recently been elucidated, several key hydrogen‐bonding interactions between the reagents were implicated but not investigated. Herein the prevalence of H‐bonding between the co‐oxidant N‐methylmorpholine N‐oxide (NMO), the alcohol substrate, water and the perruthenate catalyst is established. These observations help to rationalize the importance of drying the reagents and lead to several practical suggestions. Further exploration of the Ley–Griffith (TPAP) oxidation has unveiled a better understanding of the role N‐methylmorpholine N‐oxide (NMO) plays, not just as a co‐oxidant, but also a hydrogen bonding partner to the alcohol substrate and water. These additional attributes impact reaction performance, with important implications for the practicing synthetic chemist. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The cytochromes P450 are hemoproteins that catalyze a range of oxidative C−H functionalization reactions, including aliphatic and aromatic hydroxylation. These transformations are important in a range of biological contexts, including biosynthesis and xenobiotic biodegradation. Much work has been carried out on the mechanism of aliphatic hydroxylation, implicating hydrogen atom abstraction, but aromatic hydroxylation is postulated to proceed differently. One mechanism invokes as the key intermediate an arene oxide (and/or its oxepin tautomer). Conclusive isolation of this intermediate has remained elusive and, currently, direct formation of phenols from a Meisenheimer intermediate is believed to be favored. We report here the identification of a P450 [P450cam (CYP101A1) and P450cin (CYP176A1)]-generated arene oxide as a product of in vitro oxidation of tert-butylbenzene. Computations (CBS-QB3) predict that the arene oxide and oxepin have similar stabilities to other arene oxides/oxepins implicated (but not detected) in P450-mediated transformations, suggesting that arene oxides can be unstable terminal products of P450-catalyzed aromatic oxidation that can explain the origin of some observed metabolites. [ABSTRACT FROM AUTHOR]

N,N,N′,N′-Tetramethylethylenediamine dioxide (TMEDAO2) was explored as a more atom economical co-oxidant for the Ley–Griffith oxidation of alcohols to aldehydes. TMEDAO2 was found to selectivity oxidise benzylic and allylic alcohols in comparable yields to that of the standard Ley–Griffith co-oxidant (NMO). Importantly TMEDAO2 facilitated tandem Ley–Griffith-Wittig reactions with stabilised ylides, in good to excellent yields, without the requirement of anhydrous conditions. [ABSTRACT FROM AUTHOR]

A non-hygroscopic tetraphenylborate salt of N-methylmorpholine- N-oxide (NMO) is reported (NMO ⋅TPB), which modulates the standard Ley-Griffith oxidation such that benzylic and allylic alcohols are oxidised selectively. An attractive feature of this new protocol is that anhydrous conditions are not required for this selective tetra- n-propylammonium perruthenate (TPAP) oxidation, superseding the requirement of molecular sieves. [ABSTRACT FROM AUTHOR]

The Cover Feature shows the catalytic cycle of the Ley–Griffith oxidation, which like the site of the upcoming Heron8 conference on reactive intermediates and unusual molecules being held at Australia's iconic Uluru, works best under dry conditions. Extensive reaction monitoring has demonstrated that removal of product water by molecular sieves prevents sequestration of the co‐oxidant N‐methylmorpholine oxide (NMO) and decomposition of the tetrapro‐pylammonium perruthenate (TPAP) catalyst, leading to practical recommendations for synthetic chemists. Cover design by Kylie Agnew‐Francis. More information can be found in the Communication by P. V. Bernhardt, C. M. Williams et al. [ABSTRACT FROM AUTHOR]

Activated alcohols are efficiently oxidized under standard Ley-Griffith conditions to aldehydes or ketones, resp., using the title dioxide (TMDD) as the oxidizing agent. [ABSTRACT FROM AUTHOR]

A novel NMO complex is discovered, which modulates the Standard Ley-Griffith oxidation such that benzylic and allylic alcohols are oxidized with considerable selectivity over primary and secondary alcohols. [ABSTRACT FROM AUTHOR]

A novel non-hygroscopic DABCO N-oxide tetraphenylborate proves superior as co-oxidant in the Ley-Griffith (TPAP) oxidation of benzylic and allylic alcohols under non-anhydrous conditions. [ABSTRACT FROM AUTHOR]