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In this work, we investigated the catalytic effects of a Sharpless dimeric titanium (IV)–tartrate–diester catalyst on the epoxidation of allylalcohol with methyl–hydroperoxide considering four different orientations of the reacting species coordinated at the titanium atom (reactions R1–R4) as well as a model for the non-catalyzed reaction (reaction R0). As major analysis tools, we applied the URVA (Unified Reaction Valley Approach) and LMA (Local Mode Analysis), both being based on vibrational spectroscopy and complemented by a QTAIM analysis of the electron density calculated at the DFT level of theory. The energetics of each reaction were recalculated at the DLPNO-CCSD(T) level of theory. The URVA curvature profiles identified the important chemical events of all five reactions as peroxide OO bond cleavage taking place before the TS (i.e., accounting for the energy barrier) and epoxide CO bond formation together with rehybridization of the carbon atoms of the targeted CC double bond after the TS. The energy decomposition into reaction phase contribution phases showed that the major effect of the catalyst is the weakening of the OO bond to be broken and replacement of OH bond breakage in the non-catalyzed reaction by an energetically more favorable TiO bond breakage. LMA performed at all stationary points rounded up the investigation (i) quantifying OO bond weakening of the oxidizing peroxide upon coordination at the metal atom, (ii) showing that a more synchronous formation of the new CO epoxide bonds correlates with smaller bond strength differences between these bonds, and (iii) elucidating the different roles of the three TiO bonds formed between catalyst and reactants and their interplay as orchestrated by the Sharpless catalyst. We hope that this article will inspire the computational community to use URVA complemented with LMA in the future as an efficient mechanistic tool for the optimization and fine-tuning of current Sharpless catalysts and for the design new of catalysts for epoxidation reactions. [ABSTRACT FROM AUTHOR]

In this work, we investigated the catalytic effects of a Sharpless dimeric titanium (IV)–tartrate–diester catalyst on the epoxidation of allylalcohol with methyl–hydroperoxide considering four different orientations of the reacting species coordinated at the titanium atom (reactions R1–R4) as well as a model for the non-catalyzed reaction (reaction R0). As major analysis tools, we applied the URVA (Unified Reaction Valley Approach) and LMA (Local Mode Analysis), both being based on vibrational spectroscopy and complemented by a QTAIM analysis of the electron density calculated at the DFT level of theory. The energetics of each reaction were recalculated at the DLPNO-CCSD(T) level of theory. The URVA curvature profiles identified the important chemical events of all five reactions as peroxide OO bond cleavage taking place before the TS (i.e., accounting for the energy barrier) and epoxide CO bond formation together with rehybridization of the carbon atoms of the targeted CC double bond after the TS. The energy decomposition into reaction phase contribution phases showed that the major effect of the catalyst is the weakening of the OO bond to be broken and replacement of OH bond breakage in the non-catalyzed reaction by an energetically more favorable TiO bond breakage. LMA performed at all stationary points rounded up the investigation (i) quantifying OO bond weakening of the oxidizing peroxide upon coordination at the metal atom, (ii) showing that a more synchronous formation of the new CO epoxide bonds correlates with smaller bond strength differences between these bonds, and (iii) elucidating the different roles of the three TiO bonds formed between catalyst and reactants and their interplay as orchestrated by the Sharpless catalyst. We hope that this article will inspire the computational community to use URVA complemented with LMA in the future as an efficient mechanistic tool for the optimization and fine-tuning of current Sharpless catalysts and for the design new of catalysts for epoxidation reactions.

A convergent and flexible synthetic route for the synthesis of C3–C12 fragment of iriomoteolide-1a is described. The key steps are: Mannich reaction, Keck asymmetric allylation, Sharpless asymmetric epoxidation and cross-metathesis protocol.

We describe a new and straightforward approach to the formal synthesis of the hepatitis B virus inhibitor entecavir, an important hepatitis B drug, in ten steps overall. Key features of the route are a Morita–Baylis–Hillman reaction, a Sharpless asymmetric epoxidation, a reductive epoxide opening of an α,β-epoxy ketone, and a Riley selenium dioxide oxidation. [ABSTRACT FROM AUTHOR]

Abstract In this work, new heterogeneous catalysts intended for enantioselective Sharpless epoxidation were prepared. The catalysts are based on Ti(IV) complexes of cross-linked swellable spherical copolymer beads of styrene with ethyl-(4-vinylbenzyl)-L-tartrate, or with ethyl-(2 R ,3 R)-2,3-dihydroxy-4-oxo-5-(4-vinylphenyl)pentanoate. These catalysts were tested in epoxidation of cinnamyl alcohols. High conversion (up to 99%) and high enantioselectivity (up to 99% ee) were achieved in the case of catalysts based on copolymers of styrene with ethyl-(4-vinylbenzyl)-L-tartrate (5, 20, 50%). Unfortunately, the copolymers lost their enantioselectivity due to the leaching of L-tartrate, caused by alcoholysis of ester bond. This problem has been overcome by replacing the ester bond by a stable keto bond. The prepared catalyst based on the copolymer of styrene with ethyl-(2 R ,3 R)-2,3-dihydroxy-4-oxo-5-(4-vinylphenyl)pentanoate (20%) achieved a similarly high conversion and enantioselectivity as in the previous case (up to 99%, up to 99% ee) and was successfully recycled. [ABSTRACT FROM AUTHOR]

A convergent and flexible synthetic route for the synthesis of C3–C12 fragment of iriomoteolide-1a is described. The key steps are: Mannich reaction, Keck asymmetric allylation, Sharpless asymmetric epoxidation and cross-metathesis protocol. [ABSTRACT FROM AUTHOR]

A convergent and stereoselective approach for the synthesis of C1-C11, C12-C22, and C23-C28 fragments of cytotoxic natural products cruentaren A and B are accomplished. Highlights of the strategy include a Sharpless epoxidation followed by a regioselective opening of epoxide to generate anti and syn -stereochemistry at C9-C10 and C15-C16, an Alder-Rickert reaction between a 1,5-dimethoxy-1,4-cyclohexadiene and dienophile to construct the aromatic ring, and a lithium-mediated aldol reaction to install the C17-C18 anti -stereochemistry. The synthesis of C1-C11 and C12-C22 fragments proceed with a longest linear sequence of 10 and 17 steps from commercially available 2-butyne-1,4-diol and cis -2-butene-1,4-diol respectively. [ABSTRACT FROM AUTHOR]

A stereoselective synthesis of (6R,7R,8S)-8-chlorogoniodiol has been achieved in a linear sequence of 12 steps and 19.8% overall yield from cinnamyl alcohol. The key steps include Sharpless asymmetric epoxidation, regioselective ring opening of epoxide, indium-mediated Barbier allylation, and Still-Gennari olefination. [ABSTRACT FROM AUTHOR]

Conversion of fatty acid hydroperoxides to epoxyalcohols is a well known secondary reaction of lipoxygenases, described for S-specific lipoxygenases forming epoxyalcohols with a trans-epoxide configuration. Here we report on R-specific lipoxygenase synthesis of a cis-epoxyalcohol. Although arachidonic and dihomo-γ-linolenic acids are metabolized by extracts of the Caribbean coral Plexaura homomalla via 8R-lipoxygenase and allene oxide synthase activities, 20:3ω6 forms an additional prominent product, identified using UV, GC-MS, and NMR in comparison to synthetic standards as 8R,9S-cis-epoxy-10S-erythro-hydroxy-eicosa-11Z,14Z-dienoic acid. Both oxygens of 18O-labeled 8R-hydroperoxide are retained in the product, indicating a hydroperoxide isomerase activity. Recombinant allene oxide synthase formed only allene epoxide from 8R-hydroperoxy-20:3ω6, whereas two different 8R-lipoxygenases selectively produced the epoxyalcohol.A biosynthetic scheme is proposed in which a partial rotation of the reacting intermediate is required to give the observed erythro epoxyalcohol product. This characteristic and the synthesis of cis-epoxy epoxyalcohol may be a feature of R-specific lipoxygenases.

A stereoselective synthesis of the polyol side chain (C(1) - C(28)) of amphidinol 3 has been accomplished following Sharpless epoxidation, Crimmins aldol reaction, Jacobsen kinetic resolution, Sharpless asymmetric dihydroxylation, and our own reaction for the synthesis of a chiral allylic alcohol from an epoxy alcohol. The olefin functionality was introduced by a cross metathesis and Julia- Kocienski olefination. [ABSTRACT FROM AUTHOR]

Amphidinolide N, the structure of which has been recently revised, is a 26-membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10-epimer of the proposed structure of amphidinolide N, we have synthesized the C1-C13 subunit enantio- and diastereoselectively. Key reactions include an l-proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao-Fleming oxidation. To aid late-stage manipulations, we also developed the 4-( N-benzyloxycarbonyl- N-methylamino)butyryl group as a novel ester protective group for the C9 alcohol. [ABSTRACT FROM AUTHOR]

The stereospecific total synthesis of the pro-resolving and tissue-regenerative Protectin sulfido-conjugates: 16 R ,17 S -PCTR1, 16 R ,17 S -PCTR2, and 16 R ,17 S -PCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 16 S ,17 S -epoxy-Protectin methyl ester was synthesized using the Sharpless catalytic asymmetric epoxidation to generate the chiral centers at C16 and C17. A Cs 2 CO 3 promoted coupling provided the skipped diyne intermediate. Wittig reactions and epoxide opening with glutathione, l -cysteinylglycine, and l -cysteine methyl ester hydrochloride, respectively, were the key steps in the synthesis. [ABSTRACT FROM AUTHOR]

The total synthesis of the nonenolide xyolide is described as a convergent synthesis in 16 steps from the commercially available starting material butane-1,4-diol. The key reactions involved are: Sharpless asymmetric epoxidation, Pinnick oxidation, acid-mediated nucleophilic regioselective epoxide ring opening, Steglich esterification, and ring-closing metathesis. [ABSTRACT FROM AUTHOR]

Homogeneous linear poly(tartrate ester) ligands provide high chemical yields and enantiomeric excesses in the epoxidation of trans-hex-2-en-1-ol using Ti(OPri)4-tert-butyl hydroperoxide. Branched poly(tartrate ester) can be use as heterogeneous ligands in the epoxidation of trans-hex-2-en-1-ol using Ti(OPri)4-tert-butyl hydroperoxide. Removal and recovery of the polymer catalyst is a simple filtration at the end of reactions.

Using a one-pot Sharpless asymmetric epoxidation/regioselective epoxide ring-opening as a key step, the protecting-group-free total synthesis of goniothalesdiol A was accomplished in only three steps starting from commercially available trans -cinnamaldehyde in 55.1% overall yield. In 6 previously reported total syntheses, 6–11 steps were required. [ABSTRACT FROM AUTHOR]

Abstract: A stereoselective synthesis of tetrahydropyran–tetrahydrofuran (THP–THF) core 2 of (+)-muconin (1) has been achieved using Prins cyclization as a key step to construct tetrahydropyran moiety. Other important transformations such as Wittig olefination, Sharpless epoxidation, regio-, and stereoselective exo-cyclization of the epoxy alcohol, titanocene induced regioselective deoxygenation of 2,3-epoxy alcohol, Grignard reaction, and Barton–McCombie reaction are successfully employed to accomplish the synthesis of THP–THF core 2. [Copyright &y& Elsevier]

A stereoselective synthesis of (5 S,6 S)-6-[(2 S,5 S,7 R,8 E,10 E)-5-(benzyloxy)-7-{[( tert-butyl)dimethylsilyl]oxy}-11-phenylundeca-8,10-dien-2-yl]-5-ethyl-5,6-dihydro-2 H-pyran-2-one (=(+)-9- O-benzyl-11- O-[( tert-butyl)dimethylsilyl]bitungolide F) is reported. The strategy involves Gilman reaction, olefin cross-metathesis, and HornerWadsworthEmmons olefination as key steps. [ABSTRACT FROM AUTHOR]

An efficient stereoselective total synthesis of (+)-Cephalosporolide D (2) from commercially available and inexpensive starting material, (±)- propylene epoxide, is described. The key steps involved in this synthesis are Sharpless epoxidation and Yamaguchi macrolactonization as key steps. [ABSTRACT FROM AUTHOR]

A stereoselective total synthesis of multiplolide A ( 1) and of its diastereoisomer 2 was described from easily accessible starting materials ( Schemes 2- 4). The synthetic strategy involves a Jacobsen resolution, Sharpless epoxidation, Swern oxidation, Yamaguchi reaction, and ring-closing metathesis (RCM). [ABSTRACT FROM AUTHOR]

The first stereoselective total synthesis of the naturally occurring anti-emetic diarylheptanoid (3 R,5 R)-1-(4-hydroxyphenyl)-7-phenylheptane-3,5-diol ( 1) was accomplished starting from 4-hydroxybenzaldehyde and involving a Sharpless kinetic resolution and an asymmetric epoxidation as the key steps ( Scheme 2). The enantiomer 1a of this compound was also simultaneously prepared. [ABSTRACT FROM AUTHOR]

The first enantioselective total synthesis and a concise racemic synthesis of zenkequinone B are reported here by utilizing a sequential enyne metathesis, Diels-Alder and aromatization reactions. [ABSTRACT FROM AUTHOR]

Abstract: The first total synthesis of (−)-bitungolide E is described. The key steps include a Myers’ alkylation, modified Evans’ syn aldol-reaction, using Crimmins protocol, Sharpless asymmetric epoxidation and ring-closing metathesis reaction. [Copyright &y& Elsevier]

Abstract: A convergent stereoselective total synthesis of (+)-anamarine via cross-metathesis (CM) protocol starting from 2-butyn-1,4-diol and vinyl lactone is reported. Other key features of the strategy include the use of Sharpless asymmetric epoxidation, Sharpless dihydroxylation, and Red-Al reduction. [ABSTRACT FROM AUTHOR]

Abstract: The first stereoselective total synthesis of synargentolide A isolated from Syncolostemon argenteus has been achieved from commercially available (R)-benzyl glycidyl ether using Sharpless asymmetric epoxidation and cross-metathesis reactions as the key steps. Comparing the spectral data of the synthesized and naturally occurring synargentolide A, the C4′ and C6′- stereogenic centers of the natural synargentolide A were assigned a corrected anti relationship. [Copyright &y& Elsevier]

Abstract: Introduction in therapy of the naturally occurring trioxane artemisinin opened a new era in malaria treatment and prompted the development of semisynthetic and synthetic derivatives characterized by the presence of the key peroxide bridge. The 1,2-dioxane ring is present in some natural endoperoxides such as plakortin and dihydroplakortin, which are endowed with interesting antimalarial properties. Here we describe the development of a versatile stereocontrolled synthetic strategy to 1,2-dioxanes functionalized at the critical C3, C4, and C6 positions, potentially useful for the development of innovative antimalarials. [Copyright &y& Elsevier]

Abstract: A highly stereoselective asymmetric total synthesis of marine polypropionate (−)-baconipyrone C has been achieved. Utilization of desymmetrization technique to create five stereogenic centres, Sharpless epoxidation, Gilman''s reaction and resolution of methyl group using enzyme PS-C is the highlight of the synthesis. [Copyright &y& Elsevier]

Abstract: The heterogeneous sharpless-type catalyst was prepared by an in situ method using MCM-48 as the support. The influence of the incorporation process on the structure of MCM-48 was studied by the XRD, FT-IR, 29Si MASNMR and N2 adsorption–desorption. The obtained materials showed the definite catalytic activity on the epoxidation of allyl alcohol under the system of acetone (solvent) and peroxycarbamide (oxidant). [Copyright &y& Elsevier]

Abstract: Radical-mediated opening of chiral 2,3-epoxy alcohols, containing suitably positioned β-(alkoxy)acrylate moieties, using Cp2TiCl triggered intramolecular cyclization to give tetrahydrofuran and tetrahydropyran moieties. [Copyright &y& Elsevier]

Abstract: The synthesis of (4,5,6-13C)-deoxymannojirimycin is described. The route employed is based on Sharpless asymmetric epoxidation of (1,2,3-13C)(E)-2,4-pentadien-1-ol and uses ring-closing metathesis as a key step. The labeled compound may be easily used for protein-binding experiments using NMR spectroscopic methods. [Copyright &y& Elsevier]

Twenty five years before the tetrahedral structure for carbon was proposed in 1874 to explain the optical activity and other properties of organic compounds, Louis Pasteur discovered the existence of enantiomerism in tartaric acid. He separated the oppositely shaped crystals of tartaric acid by handpicking, found their optical rotation to be in opposite directions, and concluded that this optical property was attributable to the existence of two oppositely shaped tartaric acid molecules. Thus the new subject of stereochemistry was heralded. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of densely functionalized acyclic long chain terminal alkenic alcohols was achieved by reductive opening of glycal derived 2,3-epoxy-1-iodides, with commercial zinc dust alone in a short reaction time with excellent yields involving a simple reaction procedure and easy work-up. A mechanism involving an organometallic intermediate is proposed. [Copyright &y& Elsevier]