Asymmetric Dihydroxylation Reaction Research Articles

First enantioselective total synthesis of glutinone and its C(7) and C(11) epimers

A facile and efficient asymmetric synthesis of glutinone 1 and its C(7) and C(11) epimers 1b– d is presented, using the Sharpless asymmetric dihydroxylation reaction as the key step. By comparing the spectral data of the natural product with that of the synthetic samples, we could confirm the absolute configuration of glutinone 1.

A simple and effective soluble polymer-bound ligand for the asymmetric dihydroxylation of olefins: DHQD-PHAL-OPEG-OMe

The synthesis of a novel soluble polymer-bound ligand DHQD-PHAL-OPEG-OMe and its application in the catalytic asymmetric dihydroxylation (AD) reaction are described. 1,4-Dichlorophthalazine was used as the coupling reagent to connect dihydroquinidine and polyethylene glycol monomethyl ether (MW=5000, Fluka) while providing an aromatic group at the 9- O-position of dihydroquinidine. Enantiomeric excesses for trans-disubstituted olefins in the AD reaction, with K 3Fe(CN) 6 as secondary oxidant, are up to 98%.

Enantioselective synthesis for the (-)-antipode of the pyrazinone marine alkaloid, hamacanthin A.

A short enantioselective total synthesis for the (-)-antipode of the antifungal marine alkaloid, hamacanthin A, (6R)-3,6-bis(6-bromoindol-3-yl)-5,6-dihydro-2(1H)-pyrazinone, is described. This synthesis proceeds through the coupling of 3-indolyl-alpha-oxoacetyl chloride and 3-indolyl azidoethylamine, followed by intramolecular aza-Wittig type cyclization. A concise and useful approach for the synthesis of (1R)-1-(indol-3-yl)-2-azidoethylamine using the Sharpless asymmetric dihydroxylation reaction followed by stereospecific azidation is also presented.

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.

Substrate Binding in the Asymmetric Dihydroxylation Reaction − Investigation of the Stereoselectivity in the Dihydroxylation ofCs-Symmetric Divinylcarbinol Derivatives

The mechanism of the asymmetric dihydroxylation (AD) reaction has been hotly disputed. We have studied the stereochemical outcome of the AD reaction on a series of Cs-symmetric divinylcarbinol derivatives in order to shed light on the binding mode of the substrate to the osmium tetroxide−ligand complex. The product distribution is dependent on the size of the allylic substituent, and on the type and class of ligand. It is postulated that the diastereospecificity of the reactions originates from attractive forces between the substrate and the ligand. These interactions are independent of the interactions responsible for the enantioselectivity in the AD reaction.

Enantioselective synthesis of ( S)- and ( R)-α-methylserines: application to the synthesis of ( S)- and ( R)- N-Boc- N, O-isopropylidene-α-methylserinals

This report describes the synthesis of enantiomerically pure ( S)- and ( R)-α-methylserines on a multigram scale, starting from the Weinreb amide of 2-methyl-2-propenoic acid and using a stereodivergent synthetic route that involves a Sharpless asymmetric dihydroxylation reaction. As a synthetic application of these quaternary α-amino acids, they were used as starting materials in the synthesis of the well-known valuable homochiral ( S)- and ( R)- N-Boc- N, O-isopropylidene-α-methylserinal building blocks.

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.

Total synthesis of (+)-zaragozic acid C.

A total synthesis of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous acetonide deprotection-dithiane removal-ketalization procedure leading exclusively to the 2, 8-dioxabicyclo[3.2.1]octane core 34; and a novel triple oxidation procedure allowing installation of the tricarboxylic acid.

Total synthesis of asimicin and bullatacin.

The efficient total synthesis of asimicin, 1, and bullatacin, 2, has demonstrated the advantages of three different strategies for the synthesis of the tricyclic intermediates 6 and 7, which represent the key fragment of the bis-THF Annonaceous acetogenins. The naked carbon skeleton strategy is based on the production of all asymmetric centers by selective placement of the oxygen functions onto an unsaturated, nonfunctionalized carbon skeleton. Diversity in this approach arises from the relative timing of highly stereoselective reactions, such as the Sharpless asymmetric dihydroxylation (AD) reaction, the Kennedy oxidative cyclization (OC) with rhenium(VII) oxide, the Mitsunobu-type alcohol epimerization reaction, and the Williamson etherification reaction. The convergent strategy, which is based on the combinatorial coupling of two series of diastereomeric fragments, to produce intermediates such as 11 and 12, enjoys the advantages of both efficiency and versatility. The third approach, which is based on partially functionalized intermediates, such as 13, combines the advantages of both the linear and the convergent strategies-synthetic efficiency and diversity.

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.

Highly enantioselective osmium dihydroxylation of unsubstituted allyl N-phenylcarbamate using AD- mix reagents

A prominent effect of the phenylcarbamoyl protecting group on the asymmetric dihydroxylation (AD) reaction was confirmed in both of the reactions of allyl N-phenylcarbamate with AD- mix-α and -β, bringing about excellent enantioselectivity (>99% ee) to give ( R)- and ( S)-glycerol 1-( N-phenylcarbamate) in quantitative yields, respectively.

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.

Expanding Synthetic Utilities of Asymmetric Dihydroxylation Reaction: Conversion of syn-Diols to syn-Amino Alcohols

Expanding Synthetic Utilities of Asymmetric Dihydroxylation Reaction: Conversion of <i>syn</i>-Diols to <i>syn</i>-Amino Alcohols

Anomalous enantioselectivity in the sharpless asymmetric dihydroxylation reaction of 24-nor-5beta-cholest-23-ene-3alpha,7alpha,12alpha-triol: synthesis of substrates for studies of cholesterol side-chain oxidation.

Recently we described a block in bile acid synthesis in cerebrotendinous xanthomatosis (CTX), a lipid storage disease related to an inborn error of bile acid metabolism. In this disease a defect in hepatic microsomal (24S) hydroxylation blocks the transformation of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into (24S) 5beta-cholestane-3alpha,7alpha,12alpha,24,25- pentol and cholic acid. Mitochondrial cholesterol 27-hydroxylation has also been reported to be abnormal in CTX subjects, but the relative importance of the enzymatic defect in this alternative microsomal pathway (namely, the 24S hydroxylation of 5beta-cholestane-3alpha,7alpha, 12alpha,25-tetrol relative to the abnormality in mitochondrial 27-hydroxylase) has not been established in CTX. To delineate the sequence of side-chain hydroxylations and the enzymatic block in bile acid synthesis, we synthesized the (23R and 23S) 24-nor-5beta-cholestane-3alpha,7alpha, 12alpha,23,25-pentols utilizing a modified Sharpless asymmetric dihydroxylation reaction on 24-nor-5beta-cholest-23-ene-3alpha, 7alpha, 12alpha-triol, a C26 analog of the naturally occurring C27 bile alcohol, 5beta-cholest-24-ene-3alpha,7alpha,12alpha-triol . Stereospecific conversion of the unsaturated 24-nor triol to the corresponding chiral compounds (23R and 23S), 24-nor-5beta-cholestane-3alpha,7alpha,12alpha,23 ,25-pentols, was quantitative. However, conversion of the unsaturated 24-nor triol to the chiral nor-pentols had absolute stereochemistry opposite to the products predicted by the Sharpless steric model. The absolute configurations and enantiomeric excess of the C26 nor-pentols and the C27 pentols (synthesized from 5beta-cholest-24-ene-3alpha,7alpha,12alpha-triol for comparison) were confirmed by nuclear magnetic resonance and lanthanide-induced circular dichroism Cotton effect measurements. These results may contribute to a better understanding of the role of the 24S-hydroxylation vs. 27-hydroxylation step in cholic acid biosynthesis.

Synthesis of novel C2 symmetrical and enantiomerically pure thiepines

Novel thiepines were synthesised using a Sharpless asymmetric dihydroxylation reaction to introduce the two chiral centres and with ring closure achieved by using sulfur diimidazole in conjunction with either a double ortho-lithiation or a double bromine/lithium exchange.

Concerning kinetic resolution by the Sharpless asymmetric dihydroxylation reaction

The transition state for the product-determining step in the Sharpless asymmetric dihydroxlation reaction is not product-like, and effective kinetic resolution can occur when one face of a chiral alkene is hindered.

ChemInform Abstract: Asymmetric Dihydroxylation Reactions Leading to Novel Chiral Ferrocene Derivatives.

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.

Synthesis of 3-hydroxy and 3-amino 2-substituted N-heterocycles via enamine oxidation and aziridination

Reaction of the N-sulfonyl heterocyclic enamines ( 1a/b) under asymmetric epoxidation and dihydroxylation reaction conditions leads to 2,3-dihydroxypyrrolidines and piperidines, ( 2a) and ( 2b). Only diols are observed under aminohydroxylation conditions, but Mn-mediated aziridination of ( 1a) provides a route to the 3-amino-2-methoxypyrrolidine derivatives ( 6) and ( 7).

Total Synthesis of Uvaricin.

The first total synthesis of naturally occurring (+)-uvaricin was achieved using three consecutive Sharpless asymmetric dihydroxylation (AD) reactions to place the necessary oxygen functions on a "naked" carbon skeleton in a regio- and enantioselectively controlled manner. The appropriate bis-THF ring system was constructed using a Williamson type etherification reaction on a functionalized bis-mesylate intermediate.

Asymmetric dihydroxylation reactions leading to novel chiral ferrocene derivatives

Several ferrocenyl alkenes were used as starting materials for asymmetric dihydroxylation reactions. Although they turned out to be unreactive employing Sharpless' standard conditions, by systematic variation of the reaction conditions the desired novel ferrocenyl diols could be obtained in good yields and in enantiomeric excesses up to >99%.