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The M06-2X DFT functional has been employed to examine monomeric titanium(IV) hydroperoxo catalysts that model the individual steps in the dimeric titanium(IV)-catalyzed Sharpless reaction. This is the first example of a transition structure for titanium(IV) tert-butyl hydroperoxide-catalyzed epoxidation that describes the molecular motion required for oxygen atom transfer. These epoxidation catalysts have been examined for both bimolecular reactions with E-2-butene and the intramolecular epoxidation of allyl alcohol. The transition structure for the bimolecular peroxyacetic acid epoxidation of E-2-butene has been shown to be spiro in nature, and likewise, the intramolecular epoxidation of allyl alcohol is also nearly spiro. The significance of the O-C-C═C dihedral angle of allyl alcohol is examined for the Ti(IV) tert-butyl hydroperoxide epoxidation mechanism. Evidence is presented that supports a hexacoordinate titanium peroxo environment that exists in the dimeric form of the Sharpless catalyst. The mechanism for a 1,3-rearrangement of the alkoxide ligand in a titanium hydroperoxide to the Ti center in concert with oxygen atom transfer of the proximal oxygen to the C═C bond of the substrate is presented. The dimerization of Ti(IV)-(R,R)-diethyl tartrate-diisopropoxide and its hydrolysis have been calculated. The mechanism for rapid ligand exchange with alkyl hydroperoxides involving the Ti(O-i-Pr)4 precursor is examined to show how the active epoxidation catalyst is produced.

The Katsuki-Sharpless epoxidation reaction is one of the most recognized chiral catalytic reactions, allowing for chiral epoxides to be used as starting materials for a series of synthetic pathways. The complete understanding of this reaction mechanism depends on the identification and description of species formed from Ti(IV) alkoxides and alkyl tartrates precatalysts. Despite previous reports on the nature of a bimetallic catalyst based on IR spectroscopy and NMR analysis, some debate remains. Therefore, we carried out mass spectrometry analysis by direct extraction of the ions from the reaction media by ESI(-)-FT-ICR and evaluated the observed ions by CID and IRMPD experiments. These techniques allowed us to detect carboxylates that correlate to the species in the reaction media and to confirm the actual presence of the titanium-tartrate complexes in solution. Our IRMPD results suggest the carboxylate dimer as an asymmetric species with two tartrates coordinated to a single Ti atom, while the other Ti center is coordinated by labile alkoxydes that could be easily exchanged by the organic peroxide and the substrate, allowing the epoxidation reaction to take place.

The unified reaction valley approach (URVA) differs from mainstream mechanistic studies, as it describes a chemical reaction via the reaction path and the surrounding reaction valley on the potential energy surface from the van der Waals region to the transition state and far out into the exit channel, where the products are located. The key feature of URVA is the focus on the curving of the reaction path. Moving along the reaction path, any electronic structure change of the reacting molecules is registered by a change in their normal vibrational modes and their coupling with the path, which recovers the curvature of the reaction path. This leads to a unique curvature profile for each chemical reaction with curvature minima reflecting minimal change and curvature maxima, the location of important chemical events such as bond breaking/forming, charge polarization and transfer, rehybridization, etc. A unique decomposition of the path curvature into internal coordinate components provides comprehensive insights into the origins of the chemical changes taking place. After presenting the theoretical background of URVA, we discuss its application to four diverse catalytic processes: (i) the Rh catalyzed methanol carbonylation&mdash, the Monsanto process, (ii) the Sharpless epoxidation of allylic alcohols&mdash, transition to heterogenous catalysis, (iii) Au(I) assisted [3,3]-sigmatropic rearrangement of allyl acetate, and (iv) the Bacillus subtilis chorismate mutase catalyzed Claisen rearrangement&mdash, and show how URVA leads to a new protocol for fine-tuning of existing catalysts and the design of new efficient and eco-friendly catalysts. At the end of this article the pURVA software is introduced. The overall goal of this article is to introduce to the chemical community a new protocol for fine-tuning existing catalytic reactions while aiding in the design of modern and environmentally friendly catalysts.

A study aimed at the synthesis and structure optimization of new, efficient, optically active β-amino alcohol ligands with a structure suitable for immobilization on magnetite nanoparticles has been carried out. The optimized homogeneous amino alcohol catalysts 13a and 13b, the chirality of which arises from the Sharpless epoxidation of suitable allyl alcohols, were tested by employing the well-established enantioselective amino alcohol-promoted addition of diethylzinc to benzaldehyde, giving the corresponding benzyl alcohol with nearly quantitative yield and ee = 95%. Then, their broad applicability as chiral catalysts was evaluated by carrying out the same reaction on a family of aldehydes, including variously substituted aromatic ones as well as an aliphatic analogue. The results have confirmed the validity of the fine-tuning process performed on ligands 13a and 13b. In fact, both exhibited excellent catalytic activity as demonstrated by the chemical yields and ee obtained from all the tested aldehydes, almost independent of the position and type of substitution in the aromatic ring.

In order to better understand the epoxide-formation step of the Sharpless epoxidation process, a set of 263 oxygen-transfer reactions reflecting the complexity of the Sharpless epoxidation process were studied using density functional theory (DFT) and Bader's quantum theory of atoms in molecules (QTAIM). The diversity within these reactions reflects the different ligands in the coordination sphere of vanadium and also different substrates (alkene and an allylic alcohol both free and in the form of an alcoxo ligand). The transition states for 76 of these reactions were also characterized using DFT and QTAIM, allowing for an estimation of the impact of the different ligands and substrates on the activation barriers. A smaller subset of the latter was further subjected to an ab initio molecular dynamics (AIMD) simulation coupled to QTAIM analysis. The results show that the type of active catalyst plays an important role in the thermodinamic outcome of these reactions, with vanadium(V) tert-butylhydroperoxide adducts being responsible for the most exoenergetic reactions. On the other hand, the different ligands tested play only a limited role in modulating the thermodynamics and kinetics of these reactions. Moreover, no evidence was found to support a thermodynamic or kinetic preference for the epoxidation of an allylic alcohol over that of an unfunctionalized alkene. However, the results suggest that the reaction path is strongly influenced by the orientation of the substrate upon approximation to the active catalyst, confirming the well-known regioselectivity of the Sharpless epoxidation process.

A facile and concise synthesis of β-carboline alkaloids, such as (–)-isocyclocapitelline and (+)-cyclocapitelline, has been achieved from commercially available geraniol through a unified strategy. The key steps involved in this synthesis are Sharpless epoxidation, intramolecular ring opening of epoxide, Pictet-Spengler reaction, and dehydrogenative aromatization using 10% palladium/carbon in xylene under neutral conditions.

The stereoselective synthesis of resolvin D4 (RvD4) was achieved using the Wittig reaction of the C1–C10 dienal with the known C11–C22 phosphonium salt. The (S,E)-enantiomer (S)-10, corresponding to the C1–C8 part, was synthesized in 95% ee by the asymmetric transfer hydrogenation reaction of the corresponding acetylenic ketone followed by Red-Al reduction. Sharpless epoxidation of this alcohol using Ti(O-i-Pr)4/l-(+)-DIPT as a catalyst produced anti epoxy alcohol with >99% ee as the sole product in 82% yield. A subsequent functional group manipulation, including removal of the PMB group, produced the alcohol, which upon Swern oxidation afforded anti 4-hydroxy-5-TBS-oxy enal via epoxide ring opening of the resulting aldehyde. The Horner–Wadsworth–Emmons reaction was used to add the C9–C10 enal part to this aldehyde, and the resulting dienal was subjected to the Wittig reaction with C11–C22 phosphonium salt to furnish the entire structure of RvD4. Conversion of the primary alcohol to the methyl ester and d...

The stereospecific total synthesis of the pro-resolving and tissue-regenerative Protectin sulfido-conjugates: 16R,17S-PCTR1, 16R,17S-PCTR2, and 16R,17S-PCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 16S,17S-epoxy-Protectin methyl ester was synthesized using the Sharpless catalytic asymmetric epoxidation to generate the chiral centers at C16 and C17. A Cs2CO3 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.

A novel autophagy inducer, (+)-epogymnolactam (1), was first synthesized from cis-4-benzyloxy-2-butene-1-ol (2) in eight steps. A reliable preparation of optically pure epoxy alcohol (+)-3 from monobenzyl derivative (2) was established by a tandem strategy, Sharpless epoxidation/lipase kinetic resolution.

Nannocystin A is a novel 21-membered macrolactone isolated from myxobacterium Nanocystis sp. It is a potent elongation factor 1 inhibitor and inhibits cancer cell line growth at nanomolar concentrations. In this work, a concise asymmetric total synthesis of nannocystin A has been developed, which features Sharpless epoxidation, Stille coupling, and final macrolactamization.

Starting from the conveniently available ex-chiral pool building block (R,R)-hexa-1,5-diene-3,4-diol, the ten-membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation.

The total synthesis of enantiomer of pyrenophorol, non-natural isomer of pyrenophorol, has been accomplished in 12 steps from enantiomerically pure ( R )-Propylene oxide prepared by hydrolytic kinetic resolution. Other key steps are Sharpless epoxidation, reductive elimination of iodoepoxide, and Mitsunobu reaction for the construction of the macrolactone.

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.

A stereocontrolled, facile and high-yield approach for producing (+)-altroDNJ, has been developed starting from the inexpensive commercial cis 2-butene-1,4-diol. Sharpless epoxidation and a subsequent dihydroxylation were used for the introduction of all stereocentres; finally, the ring closure under basic conditions afforded the piperidine heterocycle.

Progress toward the synthesis of the microtubule-stabilizing agent, (-)-zampanolide, is reported. Construction of the 2,6-cis-tetrahydropyran ring was accomplished utilizing ether transfer methodology in conjunction with an intramolecular radical cyclization reaction. Efficient installation of the C16-C20 side chain relied on a one-pot cross-metathesis/olefination sequence, Sharpless epoxidation, and selective reduction of a vinyl epoxide.

A protecting group free asymmetric total synthesis of (−)-venlafaxine is reported. The strategy employs Sharpless epoxidation and regio-selective epoxide ring opening by an in situ generated Gilman reagent as key steps. This paper reports a 53% overall yield in 6 steps for total synthesis of (−)-venlafaxine.

An efficient and practical total synthesis of (+)-spirolaxine methyl ether is described. The phthalide-aldehyde 3 has been prepared via the Diels-Alder reaction between 1,4-unconjugated diene 5 and a long-chain acetylenic dienophile 6. The carbon framework of spiroketal sulfone 4 has been constructed from monobenzyl protected 1,5-pentanediol and the stereochemistry in both the phthalide portion and the spiroketal portion has been established by the Sharpless asymmetric epoxidation.

An efficient formal total synthesis of the marine natural product palmerolide A is reported herein, involving 24 longest linear steps. The key features of our synthesis involve a combination of Sharpless epoxidation and Shimizu reaction to construct the syn aldol moiety, a Julia–Kocienski reaction to construct the diene, and ring-closing metathesis to form the macrocycle.

An efficient protocol for the asymmetric synthesis of triacetyl- d - erythro -sphingosine and D-1-deoxyallonojirimycin has been developed starting from commercially available propargyl alcohol. The key steps involved Sharpless asymmetric epoxidation and Miyashita C2 selective endo -mode azide opening of the 2,3-epoxy alcohol.

A stereodivergent total synthesis of the Delta(13)-9-isofurans has been developed. The four core substituted tetrahydrofurans were prepared by the Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation followed by cascade cyclization. The relative configuration at C-8 was inverted by oxidation followed by immediate L-Selectride reduction. The relative configuration of the C-15 diastereomers was assigned by (S)-Binol/LAH/EtOH reduction of the corresponding enone. This synthesis of the Delta(13)-9-isofurans will provide sufficient material for further investigation of their biological activity.

The first total synthesis of 9-membered macrolide, stagonolide-F (3), starting from commercially available 1,5-pentane diol is reported. A combination of Jacobsen's hydrolytic kinetic resolution (HKR) and Sharpless epoxidation is used for the creation of two stereogenic centers, while ring-closing metathesis (RCM) strategy was used for the construction of the lactone ring. The molecule synthesized exhibited potent antifungal, antibacterial and cytotoxic activities against all the tested strains.

A number of isomeric bistetrahydrofuran analogues were prepared from triepoxy farnesyl bromides by a zinc-initiated reduction-elimination and in situ Lewis acid-promoted cascade cyclization.

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, Si-29 MASNMR and N-2 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). (C) 2007 Elsevier Inc. All rights reserved.

Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) were employed for coupling of segments A and B: segment A1 for the Julia coupling reaction was prepared by a combination of Sharpless asymmetric epoxidation and an epoxide-cleavage reaction with an organoaluminum reagent, while segment A2 for the NHK reaction was synthesized from optically active alcohol that had previously been prepared by lipase-catalyzed kinetic resolution. Segment B, whose structure was modified with some functional groups, was synthesized from (R)-malic acid by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation, and segment C, containing a cyclohexane moiety, was prepared by asymmetric Diels-Alder reaction. Segment B was first coupled with segment A1 via the Julia coupling reaction, but the yield was low due to unexpected epimerization. The NHK reaction of segment A2 proceeded to give the coupling product in good yield. This product was coupled with segment C via Wittig and Stille coupling reactions, and finally, phosphorylation was carried out by partial hydrolysis of a cyclic phosphate to give leustroducsin B.

Synthetic analysis of spirastrellolide E envisioned to entail a cross-metathesis union of the northern and southern hemispheres followed by a Sharpless epoxidation/methylation sequence to achieve the C(22,23) stereogenicity leads to the design of a C(1)–C(23) advanced southern hemisphere exploiting a gold-catalyzed directed spiroketalization as a key step. Stereochemical analysis of this strategic transformation provides insight on the impact of the directing group carbinol stereogenicity on the reaction efficiency and, in turn, permits the conversion of the minor isomer of the spiroketal precursor to the requisite congener for successful spiroketalization.

Condensation of a L-alanine derived delta-bromo-beta-silyloxy-propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-beta-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-alpha-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with beta-form side chain is further converted into lepadins A-C via carbon chain elongation, while the intermediate with alpha-form side chain is transformed into lepadins D, E, and H and corresponding 5'-epimers via connection with two sulfones generated from two Sharpless epoxidation products. By comparison of the rotations and NMR data, the stereochemistry of lepadins D, E, and H is assigned as 2S,3R,4aS,5S,8aR,5'R.

A multigram scale synthesis of the four stereoisomers of methyl 3-silylglycidates (epoxysilanes) with high enantiopurity is described. Key reactions include a Sharpless asymmetric epoxidation (SAE) of a trans-vinylsilane and an enzymatic resolution of a racemic cis-epoxysilane to establish the desired configurations. Few chromatographic separations (5 columns out of 13 steps) are required for purification, establishing a convenient reaction sequence for both the trans- and cis-isomers.

A simple synthesis of cis-3-hydroxy-L-proline has been achieved starting from b -alanine making use of Sharpless asymmetric epoxidation as a key step in the synthesis. cis-3-Hydroxy-L-proline is a relatively rare b -hydroxy-a -amino acid, which has been found as a component of the antibiotic teleomycin.1 In connection with the synthesis of the natural product "cyclothialidine"2, we required to synthesize the optically pure cis-3-hydroxy-L-proline in good chemical yield. Several syntheses of cis-3-hydroxy-L-proline have been reported. Apart from the enzymatic resolution3 of cisand trans-3-hydroxy proline, a variety of approaches to the synthesis of this amino acid are reported in the literature with varying degree of success and limitations.4 Most of these utilized enzymatic methods or chiron approach to get the optically pure product. We decided to study a new approach to the asymmetric synthesis of cis-3-hydroxy-Lproline 1 using Sharpless asymmetric epoxidation as a key step in the synthetic strategy. A retrosynthetic analysis of this approach is depicted in scheme-1 Cis-3-hydroxy proline can be derived from trans-3-hydroxy proline which in turn can be formed by an intramolecular cyclisation of an amino epoxide. The chiral epoxide can be generated by Sharpless epoxidation of a suitable allylic alcohol. The allylic alcohol in turn can be derived from b alanine by straightforward synthetic manipulations. The synthetic route was started with the readily available and inexpensive b -alanine. A suitable protective group for the amino group was needed which will be stable to Sharpless epoxidation conditions later in the sequence. It is well documented in the literature5 that the Boc or Cbz protected amines usually lead to the formation of cyclic urethane derivatives under these conditions. Various type of N-protecting groups that would encourage cyclization through nitrogen namely N-tosyl, N-trityl, and even unprotected derivatives have been tried but in all the cases the reaction leads to a complex mixture of products. All the problems are taken care of when nitrogen is protected both with tosyl as well as benzyl group.6 The synthetic route adopted to achieve the synthesis of 1 is presented in scheme-2. The methyl ester of b -alanine was readily converted to the N-protected methylester 2 which on reduction with lithium aluminium hydride in ether (0oC) provided the alcohol 3 in quantitative yield. The alcohol 3 was then oxidized with Dess-Martin periodinane to afford the aldehyde 4 in 97% yield while the Swern oxidation of the same compound gave the product only in 69% yield. The aldehyde 4 was allowed to react with triethylphosphono acetate7 and the trans olefin 5 was obtained in 89% yield. Initially the reduction of the unsaturated ester 5 was tried with lithium aluminium hydride in ether but it led to a mixture of allylic alcohol 6 and the corresponding saturated alcohol. However when the reduction of 5 was carried out with AlH3, generated in situ, the allylic alcohol 6 was the only product obtained in quantitative yield. Now the stage is set for carrying out Sharpless asymmetric epoxidation. The allyl alcohol 6 was treated with titanium tetraisopropoxide, tert-butyl hydroperoxide, and L-(+)-diethyl tartarate8 and the epoxy alcohol 7 was obtained in 92% yield with 98% ee. The enantiomeric excess was estimated by NMR shift reagent [Eu(hfc)3] experiments. Initially the direct oxidation of the epoxy alcohol 7 to the epoxy acid 8 with RuCl3/NaIO4 was carried out but the yield obtained in this reaction was generally poor (45% of corresponding methyl ester). Therefore the epoxy alcohol 7 was first oxidized to the aldehyde with Dess-Martin periodinane followed by oxidation with Ag2O to get the epoxy carboxylic acid 8 (91%). Compound 8 was converted to its methyl ester 9 on treatment with diazomethane in high yield. NMR experiments with chiral shift reagent [Eu(hfc)3] revealed the product 9 to have optical purity of 98% ee.

Polymers such as poly(ethylene glycol) (PEG) have proven use in a variety of applications including organic synthesis. We now disclose our investigations into the recently disputed report that PEG tartrate esters can reverse the enantioselectivity of the Sharpless asymmetric epoxidation reaction. The results presented herein have clarified that the enantioselectivity of this reaction can be reproducibly reversed solely as a function of the molecular weight of the appended PEG. By preparing a range of tartrate ligands with varying PEG chains lengths, the reversal was found to occur within a molecular weight change of only 800. As the PEG chain did not affect the inherent chirality of the ligand, the enantioreversal was proposed to occur as a result of two Ti-ligand complexes which differ in their molecularity of ligand, one monomeric in ligand and the other dimeric. Support for this hypothesis was given through equilibrium measurements which revealed that the predominant species in Ti/PEG tartrate ester mixtures is a distinct 2:1 Ti-ligand complex, as opposed to the 2:2 Ti-ligand complex of traditional Sharpless asymmetric epoxidations. In total, these data represent an unrecognized property of PEG-supported catalysts that could open up new venues in the control of asymmetric reactions by means of achiral appended polymers.

Peridinin, which was isolated from the planktonic algae dinoflagellates causing red tides, is a highly oxidized carotenoid containing an allene and a characteristic (Z)-gamma-ylidenebutenolide function in the main conjugated polyene chain in addition to functionalized cyclohexane rings at both ends of the molecule. We achieved a stereocontrolled total synthesis of peridinin by featuring the Sharpless asymmetric epoxidation under precise reaction conditions, Wittig reaction with silylfuranmethylide followed by photosensitized oxygenation, stereocontrolled Pd-catalyzed one-pot (Z)-gamma-ylidenebutenolide synthesis, and modified Julia-Kocienski olefination. This synthesis is the first example of controlling the stereochemistry of polyfunctional allenic carotenoids.

A generally applicable synthesis has been developed for 2-substituted oxirane-2-carboxylic esters, which have attracted interest as inhibitors of carnitine palmitoyltransferase-1 (CPT-1) for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). The route involves alkylation of the dianion of 2-methyl-2-propen-1-ol (methallyl alcohol) followed by Sharpless epoxidation. The utility of the method has been demonstrated by the synthesis of (R)-Etomoxir, the best known member of this class of compounds, and ethyl (R)-2-[6-(2,4dinitrophenoxy)hexyl]oxirane-carboxylate, previously synthesised only as a racemate. The high enantiomeric purity of the compounds has been demonstrated by formation of Mosher esters of the products of Sharpless epoxidation and analysis by H NMR spectroscopy.

10 pages, 7 schemes.-- PMID: 12762747 [PubMed].-- Printed version published May 30, 2003.-- Supporting information available at: http://pubs.acs.org/doi/suppl/10.1021/jo034129d, The total synthesis of phytuberin, a phytoalexin of the Solanum genus, from (−)-α-santonin is reported. The key steps include (a) reductive cleavage of the C−O bond of the γ-lactone with concomitant protection of the C1 double bond, (b) Sharpless stereocontrolled hydroxy-assisted epoxidation of allylic alcohol 6 and simultaneous deprotection of the C1 double bond, (c) a rare 4-endo-tet acid-catalyzed cyclization of an α-hydroxy epoxide, and (d) an unprecedented 4-exo selenocyclization of a homoallylic alcohol., This work was supported by the Investigation Programmes no. BQU2000-0650 and BQU2001-1665 of the Dirección General de Investigación Científica y Técnica, Spain. The inocolum of Erwinia carotovora var. carotorova (CECT 225T) was provided by the Colección Española de Cultivos Tipo.

The asymmetric synthesis of (-)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective cis-dihydroxylation using AD-mix-alpha. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.

The epoxidation of three stereolabeled methyl-substituted chiral allylic alcohols with (1,2)A and/or (1,3)A allylic strain, namely 3-methylbut-3-en-2-ol (1a), pent-3-en-2-ol (1b), and 3-methylpent-3-en-2-ol (1c), have been studied by the density-functional theory method, B3LYP/6-31+G(d,p). For each substrate we calculated the two prereaction complexes with Ti(OH)(4)/MeOOH (the oxidant model for Ti(O-i-Pr)(4)/t-BuOOH), their threo and erythro transition states for oxygen transfer, and the corresponding product complexes. For substrate 1a, the erythro transition state is 0.91 kcal/mol of lower energy than the threo one; for substrates 1b and 1c, the threo compared to the erythro transition states are by 1.05 and 0.21 kcal/mol more favorable, respectively. The threo/erythro product ratios have been estimated from the computed free energies for the competing threo and erythro transition states 3a-c in CH(2)Cl(2) solution to be 12:88 (1a), 92:8 (1b), and 77:23 (1c), which are in good accordance with the experimental values 22:78 (1a), 91:9 (1b), and 83:17 (1c). The diastereoselectivity of this diastereoselective oxyfunctionalization is rationalized in terms of the competition between (1,3)A and (1,2)A strain and the electronic advantage for the spiro transition state. In addition, solvent effects are also play a role for the diastereoselectivity at the same time.

Wilkinson's catalyst [RhCl(PPh3)3] has been used to conjugate fish oils in high yields under very mild reaction conditions. A catalyst load of 0.35 mol% of RhCl(PPh3)3, 0.43 mol% of (o-CH3C6H4)3P, and 0.87 mol% of SnCl2·2H2O in ethanol solvent at 60°C for 2 d produces 82% conjugated Norway fish oil affords 90% conjugated fish oil in 93% yield. The Sharpless epoxidation procedure has also been employed to epoxidize fish oils. Using 0.34 mol% of CH3ReO3, 8.15 mol% of pyridine, and 1.03 equivalents of aq. 30% hydrogen peroxide in methylene chloride solvent at 25°C for 6 h, the Norway fish oil ethyl ester can be 100% epoxidized in an 86% yield. The Capelin fish oil gives 100% epoxidized fish oil in a 72% yield. Decreasing the amounts of CH3ReO3 and pyridine used in the reaction results in partially epoxidized fish oils.

A series of novel hybrid compounds between indolo[b]tetrahydrofuran and imidazolium salts were prepared from tryptophol by four steps of Sharpless epoxidation, amidation, coupling and salt formation. Their structures were confirmed by H-1 NMR, C-13 NMR, HRMS and X-ray crystallographic analysis. These compounds were evaluated in vitro against a panel of human tumor cell lines. The results showed that 1-((3aR,8aS)-3,3a-dihydro-3a-hydroxy-2H-furo[2,3-b]indol-8(8aH)-yl)ethanone-3-(2-(naphthalen-2-yl)-2-oxoethyl)-5,6-dimethyl-1H-benzo[d]-imidazol-3-ium bromide (20) and 1-((3aR,8aS)-3,3a-di-hydro-3a-hydroxy-2H-furo[2,3-b]indol-8(8aH)-yl)ethanone-3-(2-naphthylmethyl)-5,6-dimethyl-1H-benzo[d]imidazol-3-ium bromide (22) exhibited higher inhibitory activity selectively against SMMC-7721, MCF-7 and SW480 cell lines compared with DDP. In particular, 1-((3aR,8aS)-3,3a-dihydro-3a-hydroxy-2H-furo[2,3-b]indol-8(8aH)-yl)ethanone-3-(2-bromobenzyl)-5,6-dimethyl-1H-benzo[d]imidazol-3-ium bromide (24) was more selective to SW-480 cell lines with IC50 values 2.0-fold lower than DDP.

The total syntheses of rubiginone A(2), C-2 and fujianmycin A are described. The synthesis involves Diels-Alder/aromatization and photo chemical reactions as key steps to construct the tetracyclic frame of benz[a]anthraquinone skeleton. Sharpless epoxidation, a copper-catalyzed regioselective epoxide opening, and enyne metathesis reactions are utilized as the key steps for the synthesis of chiral vinylcyclohexene.

The synthesis of aziridine-2-carboxylic acid derivatives of high enantiopurity is described and their synthetic utility is discussed. Ring-opening and ring-expansion reactions of both oxirane and aziridine carboxylic esters are highlighted. Convenient syntheses of a- hydroxy, b-amino and a-amino, b-hydroxy carboxylic acids with defined stereochemistry are presented. The preparation of pyrrolidinone and azetidinone derivatives from functionalized three-membered heterocycles is described. Small-ring heterocycles also serve as the basis for the synthesis of catalysts, e.g. for an asymmetric reduction and for cyclopropanation reactions. Functionalized small-ring heterocycles are highly attractive compounds from the synthetic point of view (1). Aziridine-2-carboxylic esters, for instance, are of interest as they are structurally related to a-as well as b-amino acids (2), and ring-opening reactions of oxiranecarboxylic acid derivatives allow the preparation of sterically defined a,b-functionalized carboxylic acids. The strain present in these three- membered ring compounds ensures high reactivity in ring-opening and ring-expansion reactions (2). We have developed a general and convenient synthesis of aziridine-2-carboxylic esters 1 from the corresponding oxiranecarboxylates 2 by successive treatment with sodium azide and triphenylphosphine (3). The required starting materials in turn were prepared by Sharpless epoxidation of appropriate allylic alcohols (4), followed by oxidation of the 2,3-epoxy alcohols to the corresponding carboxylic acids using either ruthenium tetroxide or a two-step process involving a Swern oxidation and subsequent oxidation with sodium chlorite (3). The sequence for the conversion of epoxy esters 2 into the aziridine esters 1 is depicted in Scheme 1.