Sharpless Catalytic Asymmetric Dihydroxylation Research Articles

Catalytic asymmetric synthesis of carboranylated diols bearing two adjacent stereocenters located at the α,β-position of o-carborane cage carbon.

Despite the great interest in carborane-containing molecules, there is a lack of literature on the generation of central chiralities, via catalytic asymmetric transformations using prochiral carboranyl substrates. Herein, we have synthesized novel optically active icosahedral carborane-containing diols via Sharpless catalytic asymmetric dihydroxylation of carborane-derived alkenes, under mild conditions. The reaction showed a good substrate scope with 74-94% yields and 92->99% ee. This synthetic approach facilitated the creation of two adjacent stereocenters respectively located at the α,β-position of o-carborane cage carbon, with a single syn-diastereoisomer. In addition, the obtained chiral carborane-containing diol product can be transformed to cyclic sulfate and can subsequently undergo a nucleophilic substitution and reduction to obtain the unexpected nido-carboranyl derivatives of chiral amino alcohols in the form of zwitterions.

A highly stereoselective synthesis of C-24 and C-25 oxysterols from desmosterol

A new highly stereoselective construction of the side chain of the C-24 and C-25 oxysterols has been achieved by using desmosterol acetate as the starting material and an improved Sharpless catalytic asymmetric dihydroxylation with 100% d.e. (diastereomeric excess) as the key step. The result is much better than the usual asymmetric dihydroxylation procedure. t-Butyl nitrite/2,2,6,6-tetramethylpiperidine N-oxyl radical/FeCl3 catalyst system was developed to activate molecular oxygen for the aerobic oxidation of 24-hydroxycholesterol and the 24-ketocholesterol was obtained in 86.2% yield. The oxidation system has never been reported before. The mechanism for the catalytic aerobic oxidation was also proposed.

Sharpless Asymmetric Dihydroxylation of Olefins in WaterSurfactant Media with Recycling of the Catalytic System by Membrane Nanofiltration

AbstractThis paper presents a new and more sustainable alternative approach for the Sharpless catalytic asymmetric dihydroxylation (AD) of olefins using a water/surfactant system as reaction media. The AD reaction was performed using several cationic and anionic surfactants allowing yields and enantiomeric excesses higher or comparable with the conventional systems (using organic mixtures). The use of this water/surfactant medium offers the additional advantage of performing the reactions without the need of a slow addition of olefins. Asymmetric dihydroxylation of 1‐hexene in a 1.5 mM sodium cholate aqueous solution, using N‐methylmorpholine N‐oxide (NMO) as co‐oxidant was selected as model system to evaluate the feasibility of recycling the Sharpless catalytic system by nanofiltration. The reaction media was processed by nanofiltration, the product was isolated in the permeate, whereas the catalytic system and surfactant were retained by the membrane and recycled through six successive reactions, improving the catalyst turn‐over number. The experimental results were compared with the ones calculated on the basis of mass balances, membrane rejections to product and reaction yields.

Asymmetric Dihydroxylation of 2‐Substituted 1‐Vinylferrocenes: The First Non‐Enzymatic Kinetic Resolution of Planar‐Chiral Ferrocenes

AbstractThe first non‐enzymatic kinetic resolution of planar chiral ferrocenes has been achieved by the Sharpless catalytic asymmetric dihydroxylation (AD) of a set of racemic 2‐substituted 1‐ethenylferrocenes 1a–d. The enantioselectivity factor krel varies from 20 to 62 [for (DHQD)2PYR ligands], and from 5 to 27 [for (DHQ)2PYR ligands]. The stereochemical outcome of the resolution can be easily predicted by the mnemonic device for AD, with the additional hypothesis that in the preferred transition state the olefin group and the upper cyclopentadiene ring of vinylferrocenes exhibit an essentially coplanar geometry.

First stereoselective synthesis of potassium aeschynomate and its no-natural stereomers

The synthesis of potassium aeshynomate and its non-natural stereomers was achieved using the Sharpless catalytic asymmetric dihydroxylation of ( Z) or ( E) vinylogous glycine as the key step. The resulting γ-amino α,β-dihydroxyester stereomer was deprotected and coupled with the caffeic acid to afford stereoselectively potassium aeshynomate or its stereomers. A detailed study of the NMR data of the different stereomers is reported that corrects the literature data.

Ionic liquids as a convenient new medium for the catalytic asymmetric dihydroxylation of olefins using a recoverable and reusable osmium/ligand.

The use of room-temperature ionic liquids (RTILs) in the Sharpless catalytic asymmetric dihydroxylation (AD) as a cosolvent or replacement of the tert-butanol was studied in detail by screening 11 different RTILs. The AD reaction is faster in 1-n-butyl-3-methylimidazolium hexafluorophosphate [C(4)mim][PF(6)] as a cosolvent than in the conventional system of tert-butanol/H(2)O. For the range of six substrates tested, comparable or even higher yields and enantiomeric excess (ee) were found using [C(4)mim][PF(6)] or 1-n-octyl-3-methylimidazolium hexafluorophosphate [C(8)mim][PF(6)] compared to the conventional solvent system. Due to high affinity of the catalytic osmium/quiral ligand system to the ionic liquid, the use of ionic liquid/water (biphasic) or ionic liquid/water/tert-butanol (monophasic) solvent systems provides a recoverable, reusable, robust, efficient, and simple system for the AD reaction. Using 1-hexene and [C(4)mim][PF(6)] as RTIL it was possible to reuse the catalytic system for 9 cycles with only a 5% of yield reduction from the first cycle, allowing an overall yield of 87%, TON = 1566, and with similar ee. Additionally, for each cycle, after extraction of the reaction mixture with diethyl ether, the osmium content in the organic phase (containing the AD product) and in the aqueous phase was in the range of the detection limit (<or=3%, <or=7 ppb) and 3-6% of initial amount, respectively. In contrast, the ionic liquid phase retained more than 90% of the osmium content of the previous cycle.

An enantioselective synthesis of the C 1C 9 segment of antitumor macrolide peloruside A

A stereocontrolled synthesis of the C 1C 9 segment of the marine natural product peloruside A is described. The key steps involve Sharpless's catalytic asymmetric dihydroxylation reaction, a chelation-controlled reduction of chiral β-alkoxy ketones to elaborate the syn-1,3-diol functionality and a ring-closing olefin metathesis of a homoallylic alcohol-derived acrylate ester to form an α,β-unsaturated δ-lactone.

An Enantioselective Total Synthesis of Phomopsolide C.

A flexible enantioselective route to highly functionalized α,β-unsaturated δ-lactones, has allowed for the synthesis of phomopsolide C. This approach derives its asymmetry from (S)-lactic acid and by applying the Sharpless catalytic asymmetric dihydroxylation to vinylfuran. The resulting diols are produced in high enantioexcess and can be stereoselectively transformed into α,β-unsaturated-δ-lactones via a short highly diastereoselective oxidation and reduction sequence. A Wittig olefination reaction was used to introduce the side chain in either cis or trans form that was further elaborated into phomopsolide C.

An enantioselective total synthesis of phomopsolide C

A flexible enantioselective route to highly functionalized α,β-unsaturated δ-lactones, has allowed for the synthesis of phomopsolide C. This approach derives its asymmetry from ( S)-lactic acid and by applying the Sharpless catalytic asymmetric dihydroxylation to vinylfuran. The resulting diols are produced in high enantioexcess and can be stereoselectively transformed into α,β-unsaturated-δ-lactones via a short highly diastereoselective oxidation and reduction sequence. A Wittig olefination reaction was used to introduce the side chain in either cis or trans form that was further elaborated into phomopsolide C.

ChemInform Abstract: A New Highly Stereoselective Construction of the Sidechain of Squalamine Through Improved Sharpless Catalytic Asymmetric Dihydroxylation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An olefination approach to the enantioselective syntheses of several styryllactones

A flexible enantioselective route to highly functionalized α,β-unsaturated δ-lactones, has allowed for the syntheses of the styryllactones: altholactone, isoaltholactone, 3-epi-altholactone, 2-epi-altholactone and 5-hydroxy goniothalamin in 2.5, 10, 5, 1 and 13% overall yields from furfural, respectively. This approach derives its asymmetry by applying the Sharpless catalytic asymmetric dihydroxylation to vinylfuran. The resulting diols are produced in high enantioexcess and can be stereoselectively transformed into α,β-unsaturated-δ-lactones via a short highly diastereoselective oxidation and reduction sequence. Wittig olefination or Julia olefination reactions were used to introduce the phenyl group side chain either cis or trans selectively and these intermediates were further elaborated into the altholactone isomers via selective epoxidation reactions.

ChemInform Abstract: Process Development of the Sharpless Catalytic Asymmetric Dihydroxylation Reaction to Prepare Methyl (2R,3S)‐2,3‐Dihydroxy‐3‐phenylpropionate.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A new highly stereoselective construction of the sidechain of squalamine through improved Sharpless catalytic asymmetric dihydroxylation

A new highly stereoselective construction of the sidechain of squalamine has been achieved by using methyl-3-keto-5α-chenodeoxycholanate ( 2 ) as the starting material and an improved Sharpless catalytic asymmetric dihydroxylation as the key step.

Process Development of the Sharpless Catalytic Asymmetric Dihydroxylation Reaction To Prepare Methyl (2R,3S)-2,3-Dihydroxy-3-phenylpropionate

A typical Sharpless catalytic asymmetric dihydroxylation (ADH) process to make methyl (2R,3S)-2,3-dihydroxy-3 phenylpropionate has been successfully developed. The ADH reaction was exothermic and complete in 2−3 h without affecting the optical purity and yield. The major impurity of methyl (2R)-hydroxy-3-keto-phenylpropionate, which may seriously damage the quality of diol, has been identified and removed properly in the process.

Enantioselective syntheses of isoaltholactone, 3-epi-altholactone, and 5-hydroxygoniothalamin.

A flexible enantioselective route to highly functionalized alpha, beta-unsaturated delta-lactones has allowed for the syntheses of the styryllactones: isoaltholactone, 3-epi-altholactone, and 5-hydroxygoniothalamin in 10%, 5%, and 13% overall yields from furfural, respectively. This approach derives its asymmetry by applying the Sharpless catalytic asymmetric dihydroxylation to vinylfuran. The resulting diols are produced in high enantioexcess and can be stereoselectively transformed into alpha,beta-unsaturated delta-lactones via a short highly diastereoselective oxidation and reduction sequence.

Syntheses of four d- and l-hexoses via diastereoselective and enantioselective dihydroxylation reactions

An expeditious approach to various protected hexoses has been developed by the use of the Sharpless catalytic asymmetric dihydroxylation reaction. Applying the Sharpless catalytic asymmetric dihydroxylation reaction on vinylfuran, diols with high enantioexcess are produced. The resulting diols can be stereoselectively transformed into either protected d- or l-mannose in five steps and approximately 39% yield from furfural. Similarly, both d- and l-talose and gulose have been synthesized in 19% overall yields, respectively. Using a modified strategy, both protected d- and l-gulo- and allo-sugar-δ-lactones were synthesized in eight steps and ∼20% overall yield from furfural.

Sharpless asymmetric dihydroxylation of 5-aryl-2-vinylfurans: application to the synthesis of the spiroketal moiety of papulacandin D.

[formula: see text] Using the Sharpless catalytic asymmetric dihydroxylation reaction on 5-aryl-2-vinylfurans, diols are produced in high enantioexcess. The resulting diols can be efficiently transformed into the spiroketal ring precursor of the antifungal compound papulacandin D. Stereoselective reduction of this precursor followed by a diastereoselective dihydroxylation completes the synthesis of a mannopyranoside isomer of a papulacandin derivative.

Enantioselective synthesis of 5-substituted α,β-unsaturated δ-lactones: application to the synthesis of styryllactones

A flexible enantioselective synthesis of highly functionalized 5-substituted α,β-unsaturated δ-lactones has been achieved by applying the Sharpless catalytic asymmetric dihydroxylation to vinylfuran as the key step. The resulting diols are produced in high enantio excess and can be stereoselectively transformed into differentially protected δ-lactones through a short reaction sequence.

Total Syntheses of All Four Stereoisomers of Piscidic AcidviaCatalytic Asymmetric Dihydroxylation of (Z)- and (E)-trisubstituted Olefins

All four stereoisomers of (2S, 3R)-(+)-piscidic acid were synthesized with high optical purity via Sharpless catalytic asymmetric dihydroxylation of (Z)- and (E)-trisubstituted olefins in 6 steps from (4-hydroxyphenyl)pyruvic acid. The Wittig reaction of methyl (4-hydroxyphenyl)pyruvate with (carbomethoxymethylene)triphenylphosphorane gave (Z)- and (E)-trisubstituted olefins in a 3:1 ratio. After protecting the phenolic hydroxyl group as the tert-butyldimethylsilyl ether, the (Z)-olefin was subjected to asymmetric dihydroxylation by using the chiral ligand, dihydroquinidine 1,4-anthraquinonediyl diether, and the reaction proceeded with 89% e.e. Desilylation and subsequent alkaline hydrolysis gave (2S, 3R)-(+)-piscidic acid. The optical purity was increased to >99% e.e. by recrystallization. The use of dihydroquinine 1,4-anthraquinonediyl diether enable (2R, 3S)-(-)-piscidic acid to be obtained. In the asymmetric dihydroxylation of the (E)-olefin, phthalazine ligands (dihydroquinidine and dihydroquinine 1,4-phthalazinediyl diethers) gave high e.e. values. Via the same deprotection procedure, (2S, 3S)-(+)-3-epi-piscidic acid and (2R, 3R)-(-)-2-epi-piscidic acid were respectively obtained.

Total Synthesis of (+)-(2S,3R)-Piscidic Acid via Catalytic Asymmetric Dihydroxylation of a Trisubstituted Olefin.

(+)-(2S,3R)-Piscidic acid was efficiently synthesized with high optical purity (90% e.e.) via Sharpless catalytic asymmetric dihydroxylation of a trisubstituted olefin in only 6 steps from commercially available 4-hydroxyphenylpyruvic acid as the starting material. The reaction proceeded with high optical purity by using the chiral ligands, dihydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether or dihydroquinidine 1,4-anthraquinonediyl diether.