Osmium-catalyzed Asymmetric Dihydroxylation Research Articles

ChemInform Abstract: Preclusion of the “Second Cycle” in the Osmium-Catalyzed Asymmetric Dihydroxylation of Olefins Leads to a Superior Process.

ChemInform Abstract: Preclusion of the “Second Cycle” in the Osmium-Catalyzed Asymmetric Dihydroxylation of Olefins Leads to a Superior Process.

ChemInform Abstract: The Osmium-Catalyzed Asymmetric Dihydroxylation: A New Ligand Class and a Process Improvement.

ChemInform Abstract: The Osmium-Catalyzed Asymmetric Dihydroxylation: A New Ligand Class and a Process Improvement.

ChemInform Abstract: Synthesis of Chiral 2,3-Disubstituted 1,4-Diazabicyclo(2.2.2)octane. New Ligand for the Osmium-Catalyzed Asymmetric Dihydroxylation of Olefins.

Abstract Chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octane (DABCO) derivatives have been synthesized and utilized as a chiral ligand for the osmium-catalyzed asymmetric dihydroxylation of olefins. Optically active diols in up to 41%ee are obtained in good yields.

Synthesis of the Macrocyclic Core of (−)-Pladienolide B

An efficient synthesis of the macrocyclic core of (-)-pladienolide B is disclosed. The concise route relies on a chiral auxiliary-mediated asymmetric aldol addition and an osmium-catalyzed asymmetric dihydroxylation to install the three oxygenated stereocenters of the macrocycle. This purely reagent-controlled and flexible strategy sets the stage for future analogue syntheses and structure-activity relationship plotting of the appealing anticancer lead structure pladienolide B.

Osmium-catalyzed asymmetric dihydroxylation by carbon dioxide-activated hydrogen peroxide and N-methylmorpholine

An improved process has been developed for the osmium-catalyzed dihydroxylation of olefins via in situ formation of NMO from NMM using CO 2 catalysis and H 2O 2. All olefins examined were selectively cis-dihydroxylated to their corresponding diols in good to excellent yields, and by the use of chiral ligands, high enantiomeric excesses were obtained.

Application of nanofiltration to re-use the sharpless asymmetric dihydroxylation catalytic system

In this paper, successive batch steps of an osmium-catalyzed asymmetric dihydroxylation reaction using Sharpless conditions and nanofiltration of post-reaction mixture were coupled, allowing us to enhance the cumulative catalyst turn over number to about 3.7 times over six cycles. The nanofiltration step provides for isolation of the chiral product, whereas the catalytic system (osmium and chiral ligand) is re-used in the following batch cycle. In this work the osmium average rejection through the selected nanofiltration membrane, Starmem™120, was 83%; this result may indicate the existence of free osmium in solution and implies residual product osmium contamination at an average value of 1.5 mg Os/g-product. Effective application of this methodology to the model reaction requires improvement of catalyst rejection, which calls for an effective complexation of osmium by the ligand. Nevertheless, the enantioselectivity of the reaction was maintained constant over the six cycles at a value of 69%.

De Novo Synthesis of 2‐Substituted syn‐1,3‐Diols via an Iterative Asymmetric Hydration Strategy.

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Dihydroxylation of 2-vinylaziridine: efficient synthesis ofd-ribo-phytosphingosine

An efficient and highly stereoselective synthesis of D-ribo-(2S,3S,4R)-phytosphingosine was accomplished in 62% overall yield starting from commercially available (2S)-hydroxymethylaziridine via osmium-catalyzed asymmetric dihydroxylation as a key step.

Recent Developments in Asymmetric Dihydroxylations

Ever since the early discoveries that highly oxidized transition-metal reagents are able to react with olefins to form oxidized organic compounds, chemists have investigated and developed novel methods for selective oxidations. The major breakthrough by Sharpless in the 1980s in discovering the osmium-catalyzed asymmetric dihydroxylation (AD) of olefins has inspired numerous researchers, and as a result this particular scientific area is currently thoroughly investigated. Nevertheless, new developments of this highly useful reaction are still being made. The intent of this review is to highlight recent developments achieved in asymmetric dihydroxylations with regards to improvement of the catalytic systems and extension of the substrate scope.

Combining Q2MM modeling and kinetic studies for refinement of the osmium-catalyzed asymmetric dihydroxylation (AD) mnemonic

The interactions between the substrate and the ligand in the Sharpless AD reaction have been examined in detail, using a combination of substrate competition experiments and molecular modeling of transition states. There is a good agreement between computational and experimental results, in particular for the stereoselectivity of the reaction. The influence of each moiety in the second-generation ligand (DHQD) 2PHAL on the rate and selectivity of the reaction has been elucidated in detail.

Osmium catalyzed asymmetric dihydroxylation of methyl trans-cinnamate in ionic liquids, followed by supercritical CO 2 product recovery

In this work, osmium-catalyzed asymmetric dihydroxylation (AD) of methyl trans-cinnamate was studied. Osmium and chiral ligand catalysts were immobilized in ionic liquid only, without any other reaction solvents, while the recovery of the product was performed by extraction with supercritical CO 2, and compared with results obtained by extractions with organic solvents such as hexane and diethyl ether. In supercritical CO 2 extraction experiments, optimal extraction pressure was found and ionic liquid chosen, so that the highest reaction yields coupled with lowest osmium content in the crude product can be achieved. Finally, recycle experiments of the same (ionic liquid + catalytic system) mixture were successfully conducted. Application of ionic liquids and supercritical CO 2 in osmium catalyzed AD allows for the isolation of the diol basically without contamination with osmium, in high yield and enantiomeric excess, and it makes possible the efficient reuse of ionic liquid solvent and the catalytic system.

Osmium-catalyzed asymmetric dihydroxylation of olefins in ionic liquids

Effective osmium-catalyzed asymmetric dihydroxylation was observed with 1,4-bis(9- O -diquininyl)phthalazine, (DQ) 2 PHAL, as the chiral ligand in the ionic liquid, 1- n -butyl-3-methylimidazolium hexafluorophosphate [bmim][PF 6 ]. It was shown that the ligand undergoes dihydroxylation during the reaction, affording a more polar ligand which remains in the ionic liquid phase, when the latter is extracted with diethyl ether, thus facilitating catalyst recycling. In contrast, when 1,4-bis(9- O -dihydroquininyl)phthalazine, (DHQ) 2 PHAL, which cannot undergo dihydroxylation, was used as the chiral ligand, the catalyst was extracted into the organic layer. The osmium-catalyzed hydroxylation of trans-stilbene in aqueous acetone-ionic liquid medium was enantioselective (85% ee) in the presence of the chiral ligand (D2OHQ) 2 PHAL. The chiral ligand was formed from a precursor under the reaction conditions and was recycled together with the ionic liquid.

Clean osmium-catalyzed asymmetric dihydroxylation of olefins in ionic liquids and supercritical CO2 product recovery

The combination of ionic liquids (ILs) as solvents in the asymmetric Sharpless dihydroxylation (AD) with the use of scCO(2) in the separation process allows a very simple, efficient, clean and robust system for the reuse of the AD catalytic system, which also does not need the use of organic solvents either for the reaction or for the separation of products and allows the isolation of the diol, in high yield and enantiomeric excess and basically without contamination with osmium.

Osmium-catalyzed asymmetric dihydroxylation of olefins in ionic liquidsThe effect of the chiral ligand structure on recyclability

Abstract Effective osmium-catalyzed asymmetric dihydroxylation was observed with 1,4-bis(9-O-diquininyl)phthalazine, (DQ)2PHAL, as the chiral ligand in the ionic liquid, 1-n-butyl-3-methylimidazolium hexafluorophosphate [bmim][PF6]. It was shown that the ligand undergoes dihydroxylation during the reaction, affording a more polar ligand which remains in the ionic liquid phase, when the latter is extracted with diethyl ether, thus facilitating catalyst recycling. In contrast, when 1,4-bis(9-O-dihydroquininyl)phthalazine, (DHQ)2PHAL, which cannot undergo dihydroxylation, was used as the chiral ligand, the catalyst was extracted into the organic layer.

Sodium chlorite as an efficient oxidant and hydroxy ion pump in osmium-catalyzed asymmetric dihydroxylation.

Sodium chlorite is an efficient stoichiometric oxidant in Sharpless asymmetric dihydroxylation. One sodium chlorite provides the reaction with the stoichiometric number of electrons and hydroxide ions needed to dihydroxylate two olefins without the consumption of any additional base. 100% conversion in sodium chlorite asymmetric dihydroxylation of styrene was achieved twice as fast as in the established Sharpless K(3)[Fe(CN)(6)] dihydroxylation. Even internal olefins were dihydroxylated fast with sodium chlorite without hydrolysis aids. Eight olefins were dihydroxylated to corresponding vicinal diols with yields and ees as good as those reported in the literature for other similar processes.

MTO and OsO4: an efficient catalytic couple for mild H2O2-based asymmetric dihydroxylation of olefins.

A novel and robust system for osmium-catalyzed asymmetric dihydroxylation of olefins by aqueous H2O2 with methyltrioxorhenium (MTO) as electron transfer mediator (ETM) has been developed. The MTO is catalyzing the H2O2 oxidation of the chiral ligand to its mono-N-oxide, which in turn reoxidizes OsVI to OsVIII. Thus the (DHQD)2PHAL plays a dual role serving as the chiral inductor as well as the tertiary amine generating the N-oxide required for the recycling of osmium. The present catalytic system gives vicinal diols in good isolated yields and high enantiomeric excess (up to 99 % ee).

A Mechanistically Designed Cinchona Alkaloid Ligand in the Osmium Catalyzed Asymmetric Dihydroxylation of Alkenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A New Approach to Osmium-Catalyzed Asymmetric Dihydroxylation and Aminohydroxylation of Olefins

Hydroxyaminosäure-Derivate dienen als chirale Liganden bei der hier vorgestellten Methode zur osmiumkatalysierten Dihydroxylierung und Aminohydroxylierung von Olefinen (siehe Schema). Dies sind die ersten asymmetrischen osmiumkatalysierten Prozesse, bei denen im zweiten Katalysezyklus ein Ligand permanent am Metallzentrum verbleibt.

A new approach to osmium-catalyzed asymmetric dihydroxylation and aminohydroxylation of olefins.

Simple hydroxyamino acid derivatives act as chiral ligands in osmium-catalyzed dihydroxylation and aminohydroxylation of olefins (see scheme). These are the first examples of asymmetric osmium-catalyzed processes proceeding in the second catalytic cycle with resident ligands on the metal center.

Synthesis of an optically active, bicyclic 2-pyridone dipeptide mimetic.

The eleven-step preparation of the bicyclic 2-pyridone dipeptide mimetic 1 [(3S)-6-(benzyloxycarbonylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-3-carboxylic acid] in optically active form (60% ee) is described. Key steps in the synthesis of 1 include the osmium-catalyzed asymmetric dihydroxylation of olefin 13 [(6-but-3-enyl-2-methoxypyridin-3-yl)carbamic acid benzyl ester] and the intramolecular cyclization of protected diol 19 [(3'R)-[6-[4'-(tert-butyldimethylsilanyloxy)-3'-hydroxybutyl]-2-methoxypyridin-3-yl]carbamic acid benzyl ester] to afford the pyridinium salt 20 [(3S)-[3-(tert-butyldimethylsilanyloxymethyl)-5-methoxy-2,3-dihydro-1H-indolizin-6-yl]carbamic acid benzyl ester trifuoromethanesulfonic acid salt]. Several alternate methods to prepare olefin 13 are also discussed.