Asymmetric Epoxidation Reaction Research Articles

Synthetic Studies on Tedanolide: Stereoselective Synthesis of the C1-C7 Fragment

Tedanolide (1), an 18-membered macrolide, was isolated by Schmitz et al. in 1984 from the Caribbean sponge Tedania ignis and structurally related 13-deoxytedanolide (2) was isolated from a Japanese sea sponge, Mycale adhaerens, by Fusetani et al. in 1991. Both tedanolide (1) and 13-deoxytedanolide (2) exhibit very potent biological activities against certain tumor cell lines. Their complex structures and distinctive biological properties make them extremely attractive targets for synthetic chemists. Recently Kalesse and Smith have reported successful total syntheses of tedanolide (1). As shown in Scheme 1, our retrosynthetic strategy for tedanolide (1) was the disconnection to two subunits 4 and 5 via cleavage at ester C-O bond and the aldol condensation transformation. The subunit 5 was envisioned to be obtained from the coupling between precursors 6 and 7. Herein we disclose our efforts in the construction of the C1-C7 fragment 6 of tedanolide (1). At first stage, we have utilized the Roush protocol as a key methodology toward fragment 6. The synthesis began with the known aldehyde 9. The Roush asymmetric crotylation upon 9 with 10 gave the desired product in 80% yield as a 92:8 mixture of two diastereomers, which was methylated to the methyl ether 11 in good yield. Ozonolysis of 11 furnished aldehyde 12. The second Roush crotylation on 12 did not yield the desired product. Instead we obtained a mixture of diastereomers (Scheme 2). Because of the observed lability of aldehyde 12 during the second crotylation, we considered the modification of the synthetic pathway. As a replacing measurement for the second Roush crotylation, we devised the combined application of Sharpless asymmetric epoxidation and Gilman cuprate reaction. As shown in Scheme 3, we established a highly stereoselective synthesis of precursor 6 via epoxide ring-opening and Mitsunobu reaction. The oxidative cleavage of the terminal vinyl group of 11 followed by immediate HornerWadsworth-Emmons reaction provided α,β-unsaturated ester 15 in 75% yield over two steps (trans:cis = 96:4). Subsequent reduction of ester 15 using DIBAL-H gave the intermediate allylic alcohol and Sharpless epoxidation upon this alcohol with Ti(OPr)4, L-DET and TBHP afforded stereoselectively epoxide 8 in nearly quantitative yield (β/α ≥ 30). Epoxide ring opening of 8 by the treatment with MeLi and CuI furnished the intermediate 1,3-diol (1,3-diol:1,2diol = 88:12) and the exposure of the resulting 1,3-diol to 16 with PPTS yielded p-methoxyphenyl acetal 17 in 70% yield. To introduce the requisite stereochemistry at C2, the

Asymmetric epoxidation, Michael addition, and triple cascade reaction using polymer-supported prolinol-based auxiliaries

The applicability of polymer-supported diphenylprolinol derivatives in directing either asymmetric epoxidation or Michael addition of suitable α,β-unsaturated substrates has been assessed. Epoxidation of cinnamaldehyde in the solid state give poorer yields and stereoselectivities than in the solution-phase systems. In contrast Michael additions of several aldehyde enolates to 2-nitro-1-arylalkenes gave results that approached or surpassed those in solution, and could be extended successfully to a three-component Michael/Michael/aldol cascade process. Comparisons of the results of pendant- versus crosslinked functionalized resins in these applications were revealing of the benefits and limitations of each, as were attempts to reuse the polymer-bound auxiliaries.

Enantioselective Organocatalytic Epoxidation Driven by Electrochemically Generated Percarbonate and Persulfate

AbstractAn organocatalytic asymmetric epoxidation reaction using iminium salt catalysts is described, in which the stoichiometric persulfate oxidant is generated electrochemically. This system offers comparable ees to the use of commercially available persulfate. Electrochemically generated percarbonate ion is also a successful and novel oxidant system for use with iminium salts.

Novel Chiral Calix[4]arenes by Direct Asymmetric Epoxidation Reaction

We report the first asymmetric synthesis of trans optically active (+) C 2 1,3-bisarylepoxide of calix[4]arene in excellent chemical yield and >99% ee, and its enantiospecific conversion to the corresponding bis-dioxolane.

First Concise Total Synthesis of 5‐Epi‐prelactone B

First short total synthesis of 5‐epi‐prelactone B has been achieved involving Sharpless asymmetric epoxidation and intramolecular hydride transfer reaction for formation of the aldol product by nonaldol chemistry as the key steps.

Attempts Towards the Synthesis of Feigrisolide B

Synthesis of lactones 3 and 4 is reported in an attempt towards the synthesis of natural product feigrisolide B. Sharpless asymmetric epoxidation and Gillman epoxide opening reactions were used for the construction of the required framework containing two stereocentres. The lactones 3 and 4 revealed that the proposed structure for feigrisolide B is incorrect. Keywords: Feigrisolide B, sharpless asymmetric epoxidation, yamaguchi cyclisation, wittig reaction, gillman epoxide opening reaction, oxidation

A Short and Efficient Synthetic Strategy for the Total Syntheses of (S)‐(+)‐ and (R)‐(–)‐Plakolide A

AbstractConcise and efficient total syntheses of anticancer agents (S)‐(+)‐Plakolide A and (R)‐(–)‐Plakolide A were accomplished in eight steps and an overall yield of 39 % starting from geraniol. The key steps in our strategy are Sharpless asymmetric epoxidation, double elimination, and Stille coupling reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Aspartate-catalyzed asymmetric epoxidation reactions.

We report enantioselective epoxidation reactions that are catalyzed by aspartic acid-containing peptides. The strategy involves the transient conversion of the aspartate carboxylic acid side chain to the corresponding peracid. Reaction of olefin with the activated catalyst regenerates that catalyst, which may be subjected to multiple turnovers through a carbodiimide-mediated dehydration pathway. Enantioselectivities of up to 92% ee are observed for a class of urethane-substituted olefins.

Amine‐Catalyzed Asymmetric Epoxidation of α,β‐Unsaturated Aldehydes

AbstractThe direct organocatalytic enantioselective epoxidation of α,β‐unsaturated aldehydes with different peroxides is presented. Proline, chiral pyrrolidine derivatives, and amino acid‐derived imidazolidinones catalyze the asymmetric epoxidation of α,β‐unsaturated aldehydes. In particular, protected commercially available α,α‐diphenyl‐ and α,α‐di(β‐naphthyl)‐2‐prolinols catalyze the asymmetric epoxidation reactions of α,β‐unsaturated aldehydes with high diastereo‐ and enantioselectivities to furnish the corresponding 2‐epoxy aldehydes in high yield with up to 97:3 dr and 98 % ee. The use of non‐toxic catalysts, water and hydrogen peroxide, urea hydroperoxide or sodium percarbonate as the oxygen sources could make this reaction environmentally benign. In addition, one‐pot direct organocatalytic asymmetric tandem epoxidation‐Wittig reactions are described. The reactions were highly diastereo‐ and enantioselective and provide a rapid access to 2,4‐diepoxy aldehydes. Moreover, a highly stereoselective one‐pot organocatalytic asymmetric cascade epoxidation‐Mannich reaction, which proceeds via the combination of iminium and enamine activation, is presented. The mechanism and stereochemistry of the amino acid‐ and chiral pyrrolidine‐catalyzed direct asymmetric epoxidation of α,β‐unsaturated aldehydes are also discussed.

Homogeneous and heterogeneous ruthenium catalysts in the synthesis of fine chemicals

Two examples of the application of ruthenium catalysts in fine chemical synthesis are given in this paper. In the first part, protocols for both asymmetric and non-asymmetric epoxidation reactions of olefins employing hydrogen peroxide as a “green” re-oxidant are described. Ruthenium pyridine-2,6-dicarboxylate complexes containing tridentate N-donor ligands are used as homogeneous catalysts. In the second part, a method for the stereoretentive hydrogenation of α-amino acids with water as a solvent is presented. The use of heterogeneous ruthenium catalysts, modified with rhenium, permits the efficient synthesis of the respective amino alcohols with high enantiomeric excess.

Self‐Supported Chiral Catalysts for Heterogeneous Enantioselective Reactions

The development of heterogeneous chiral catalysts for enantioselective reactions is highly desirable in order to overcome some drawbacks of homogeneous catalysts. Different from the conventional approaches by using various types of supports or biphasic systems for the recovery and reuse of homogeneous catalysts, a conceptually new strategy for heterogenization of homogeneous chiral catalysts, that is, a "self-supporting" approach, has been developed to use homochiral metal-organic coordination polymers generated by the self-assembly of chiral multitopic ligands with metal ions, and thus obviates the use of any support. In this concept article, the success of this "self-supporting" strategy will be exemplified in heterogeneous catalysis of asymmetric carbonyl-ene, sulfoxidation, epoxidation, and asymmetric hydrogenation reactions.

Studies on epoxidation of enantiomerically pure 2,3-dideoxy hex-2-enitols: a convenient access to highly functionalized enantiomerically pure tetrahydrofuran derivatives

A detailed comparative study on the epoxidation of enantiomerically pure allylic alcohols 8– 14 derived from their respective glycals with Sharpless, m-CPBA and Camp’s reagents was carried out in order to obtain 2,3-epoxy alcohols keeping in view the versatility of these synthons in synthetic chemistry for the preparation of various molecules of biological importance by suitable chemical transformations. During the course of this study, the Sharpless asymmetric epoxidation reaction was found to be an unprecedented alternative, due to its mild reaction conditions, for synthesizing highly functionalized enantiomerically pure tetrahydrofuran derivatives. A detailed mechanistic pathway of their formation has also been studied.

Enantioselective total synthesis of aigialomycin D

An efficient, convergent approach for the total synthesis of aigialomycin D 1 is described. Key features of the synthetic strategy include (a) a Sharpless asymmetric epoxidation reaction and selective opening of a 2,3-epoxy alcohol to elaborate the two hydroxy-bearing stereogenic centers at the C5′ and C6′ positions; (b) a Kocienski modified Julia protocol to construct the two E-configured double bonds; and (c) Yamaguchi macrolactonization to acccess the 14-membered macrocyclic ring.

A Short and Efficient Enantiomeric Synthesis of Antitumor Fused Tetrahydrofurans

AbstractA short and efficient enantiomeric synthesis of fused tetrahydrofuran derivatives is reported. The methodology is based on a regio‐ and stereoselective double exo‐cyclization of enantiomeric bis‐epoxy‐diols. The six stereocenters of the bis‐epoxy diols were introduced by the application of Katsuki–Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. In vitro cytotoxicities on HL60 human promyelocytic leukemia cells were determined for the bicyclic products. Active products showed exceptionally steep dose–response curves and DNA laddering. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Organocatalytic Asymmetric Epoxidation Reactions in Water—Alcohol Solutions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A new approach for the asymmetric total synthesis of umbelactone

The asymmetric total syntheses of (R)-(+)- and (S)-(-)-umbelactone were achieved by using the Sharpless asymmetric epoxidation reaction to generate the stereogenic center and a ring-closing metathesis (RCM) for the formation of the lactone structure. Starting from 3-methyl-2-buten-1-ol, the asymmetric total synthesis was achieved in an efficient 6-step protocol with an overall yield of 16%.

Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Esters Using an Yttrium‐Biphenyldiol Complex.

We succeeded in a catalytic asymmetric epoxidation reaction of α,β-unsaturated esters via a conjugate addition of an oxidant using 2−10 mol % of the yttirium-chiral biphenyldiol catalyst. A variety of substrates with β-aryl and β-alkyl substituents were epoxidized efficiently, yielding the corresponding α,β-epoxy esters in up to 97% yield and 99% ee.

Highly stereoselective synthesis of antitumor agents: both enantiomers of goniothales diol, altholactone, and isoaltholactone

A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans and α,β-unsaturated-δ-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulfonic acid.

Catalytic Asymmetric Epoxidation of α,β-Unsaturated Esters Using an Yttrium-Biphenyldiol Complex

We succeeded in a catalytic asymmetric epoxidation reaction of alpha,beta-unsaturated esters via a conjugate addition of an oxidant using 2-10 mol % of the yttirium-chiral biphenyldiol catalyst. A variety of substrates with beta-aryl and beta-alkyl substituents were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy esters in up to 97% yield and 99% ee.

Asymmetric Organocatalytic Epoxidation of α,β-Unsaturated Aldehydes with Hydrogen Peroxide

The first asymmetric organocatalytic epoxidation of alpha,beta-unsaturated aldehydes is presented. A chiral bisaryl-silyl-protected pyrrolidine acts as a very selective epoxidation organocatalyst using simple oxidation agents, such as hydrogen peroxide and tert-butyl hydroperoxide. The asymmetric epoxidation reactions proceed under environmental friendly reaction condition in, for example, water mixtures of alcohols, and the scope of the reaction is demonstrated by the formation of optically active alpha,beta-epoxy aldehydes in high yields and enantioselectivities >94% ee. Furthermore, the direct synthesis of the sex pheromone from an acaric mite by asymmetric epoxidation of citral is presented.