Asymmetric Epoxidation Reaction Research Articles

Conformational Analysis and Organocatalytic Activity of Helical Stapled Peptides Containing α-Carbocyclic α,α-Disubstituted α-Amino Acids.

Conformational freedom-restricted peptides, such as stapled peptides, play a crucial role in the advancement of functional peptide development. We synthesized stapled octapeptides using α-carbocyclic α,α-disubstituted α-amino acids, particularly 3-allyloxy-1-aminocyclopentane-1-carboxylic acid, as the crosslink motifs. The organocatalytic capabilities of the synthesized stapled peptides were assessed in an asymmetric nucleophilic epoxidation reaction because the catalytic activities are known to be proportional to α-helicity. Despite incorporating side-chain crosslinks, the enantioselectivities of the epoxidation reaction catalyzed by stapled octapeptides were found to be comparable to those obtained using unstapled peptides. Interestingly, the stapled peptides using α-carbocyclic α,α-disubstituted α-amino acids demonstrated higher reactivities and stereoselectivities (up to 99% ee) compared to stapled peptides derived from (S)-α-(4-pentenyl)alanine, a commonly used motif for stapled peptides. These differences could be attributed to the increased α-helicity of the former stapled peptide in contrast to the latter, as evidenced by the X-ray crystallographic structures of their N-tert-butoxycarbonyl derivatives.

Synthesis of Novel C 2 Bishydroxamic Acid Ligands and their Application in Asymmetric Epoxidation Reactions

AbstractAsymmetric oxidation reactions have significantly benefited from bishydroxamic Brønsted acid ligands, and they can proceed with remarkable stereoselectivity. Designing and synthesizing these ligands are essential for achieving high enantioselectivity in metal-catalyzed oxidation reactions. This paper presents a straightforward method for synthesizing novel phenyl-ring-centric bishydroxamic acids (BHA). A preliminary analysis of Ti-BHA-catalyzed reactions resulted in asymmetric epoxides with an exceptional enantiomeric excess (>99% ee). At the same time, ongoing experiments aim to improve the reaction conversion for enhanced overall efficiency.

Theoretical and experimental investigations of the enantioselective epoxidation of olefins catalyzed by manganese complexes

The enantioselective epoxidation of olefin by MnII(R,R-PMCP)(OTf)2, H2O2 and H2SO4 was explored by DFT calculations and experiments. Theoretical results suggest that [MnV(O)(R,R-PMCP)(SO4)]+ species with a triplet ground spin state serves as the active species for the olefin epoxidation. It can be generated by the H2SO4 assisted O-O heterolysis of MnIII(OOH) species. MnIII-persulfate is also involved in this system, but it cannot promote the olefin epoxidation directly, preferring instead to transform into MnV(O). Actually, the asymmetric epoxidation reactions with H2O2/H2SO4 or Oxone provide similar enantioselectivity in the presence of manganese catalyst. These observations further support the transformation of MnIII-persulfate to MnV(O) species.

Construction of an Asymmetric Porphyrinic Zirconium Metal-Organic Framework through Ionic Postchiral Modification.

Herein, one kind of neutral chiral zirconium metal-organic framework (Zr-MOF) was reported from the porphyrinic MOF (PMOF) family with a metallolinker (MnIII-porphyrin) as the achiral polytopic linker [free base tetrakis(4-carboxyphenyl)porphyrin] and chiral anions. Achiral Zr-MOF was chiralized through the exchange of primitive anions with new chiral organic anions (postsynthetic exchange). This chiral functional porphyrinic MOF (CPMOF) was characterized by several techniques such as powder X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, 1H NMR, energy-dispersive X-ray spectroscopy, scanning electron microscopy, and Brunauer-Emmett-Teller measurements. In the resulting structure, there are two active metal sites as Lewis acid centers (Zr and Mn) and chiral species as Brønsted acid sites along with their cooperation as nucleophiles. This CPMOF shows considerable bimodal porosity with high surface area and stability. Additionally, its ability was investigated in asymmetric catalyses of prochiral substrates. Interactions between framework chiral species and prochiral substrates have large impacts on the catalytic ability and chirality induction. This chiral catalyst proceeded asymmetric epoxidation and CO2 fixation reactions at lower pressure with high enantioselectivity due to Lewis acids and chiral auxiliary nucleophiles without significant loss of activity up to the sixth step of consecutive cycles of reusability. Observations revealed that chiralization of Zr-MOF could happen by a succinct strategy that can be a convenient method to design chiral MOFs.

A novel synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by sharpless asymmetric epoxidation method

Synthesis of (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol by the Sharpless asymmetric epoxidation reaction has been achieved. 2,4,5-Trifluorobenzaldehyde with methyl 2-(triphenyl-λ5-phosphanylidene)acetate gave methyl (E)-3-(2,4,5-trifluorophenyl)acrylate in 83% yield. The reduction of ester group with DibalH followed by Sharpless asymmetric epoxidation gave ((2R,3R)-3-(2,4,5-trifluorophenyl)oxiran-2-yl)methanol. Pd/C-catalyzed hydrogenation of epoxy alcohol furnished (2S)-3-(2,4,5-trifluorophenyl)propane-1,2-diol with >90% ee and 71% yield.

Highly enantioselective epoxidation of olefins by H2O2 catalyzed by a non-heme Fe(ii) catalyst of a chiral tetradentate ligand.

The chiral tetradentate N4-donor ligand, 1-methyl-2-({(S)-2-[(S)-1-(1-methylbenzimidazol-2-yl methyl)pyrrolidin-2-yl]pyrrolidin-1-yl}methyl) benzimidazole (S,S-PDBzL), based on a chiral dipyrrolidine backbone, has been synthesized and its corresponding Fe(ii) complex has been prepared and characterized. The X-ray structure of the complex reveals that the Fe(ii) ion is in a distorted octahedral coordination environment with two cis-oriented coordination sites occupied by (labile) triflate anions. The ability of the iron complex to catalyze asymmetric epoxidation reactions of olefins with H2O2 was investigated, using 2-cyclohexen-1-one, 2-cyclopenten-1-one, cis-β-methylstyrene, isophorone, chalcones and tetralones as substrates. Different carboxylic acids were used as additives to enhance yields and enantioselectivities, and 2-ethylhexanoic acid was found to give the best results. The catalysis results indicate that the Fe(ii) complex is capable of effecting comparatively high enantioselectivities (>80%) in the epoxidation reactions.

Chiral Calcium-Catalyzed Asymmetric Epoxidation Reactions Using Hydrogen Peroxide as the Terminal Oxidant.

Asymmetric epoxidation reactions of chalcone derivatives catalyzed by chiral calcium complexes using hydrogen peroxide were developed. The epoxidation reactions proceeded smoothly to afford the desired products in good yields with good enantioselectivities. This is the first example of chiral calcium-catalyzed asymmetric epoxidation reactions using hydrogen peroxide as the terminal oxidant.

Evidence of a Sole Oxygen Atom Transfer Agent in Asymmetric Epoxidations with Fe-pdp Catalysts

Iron complexes with chiral tetradentate ligands based on the pdp scaffold (pdp = N,N′-bis(2-pyridylmethyl)-2,2′-bipyrrolidine) are efficient and versatile catalysts for the highly enantioselective epoxidation of a wide range of olefins. The nature of the species responsible for oxygen atom transfer to the olefin in these reactions is under debate. In order to investigate this question, the enantioselectivity of the epoxidation reaction has been used as a mechanistic probe. The enantioselectivities obtained under different reaction conditions for two iron catalysts (S,S)-[Fe(CF3SO3)2(Me2Npdp)] ((S,S)Me2N1Fe) and (S,S)-[Fe(CF3SO3)2(dMMpdp)] ((S,S)dMM1Fe) have been analyzed. Reactions were performed with a series of peracids, and enantioselectivities of these reactions were compared with those obtained by combining peroxides and carboxylic acids. This analysis provides conclusive experimental evidence that the same oxidant is responsible for the asymmetric epoxidation reaction in both scenarios. The study al...

Studies Towards the Synthesis of Stereoisomer of Acremolide B

A convergent synthetic approach towards all carbon chain frame work of cyclicdepsipeptides acremolides A–D is described. The two key fragments, acyclic chain with four chiral centers and a dipeptide with two chiral centers were coupled together through an amide bond formation. Sharpless asymmetric epoxidation and Evans syn aldol reaction are the other key reactions involved in generating chiral centers.in the aliphatic side chain fragment.

Recent Advances in Iminium‐Salt‐Catalysed Asymmetric Epoxidation

Epoxides are important functional groups that are present in bioactive natural products and serve as useful building blocks for the formation of more complex molecular architectures. While asymmetric epoxidation methods have been known for four decades, in recent years there has been a drive to carry out transformations using organocatalysts. In this review we will discuss the application of iminium salts as organocatalysts in asymmetric epoxidation reactions, which has received a lot of attention over the last decade. We pay particular attention to the use of dihydroisoquinolinium salts and iminium salts based on binaphthyl and biphenyl systems in the asymmetric epoxidation of a broad range of olefin substrates.

(Salen)Mn(III) Catalyzed Asymmetric Epoxidation Reactions by Hydrogen Peroxide in Water: A Green Protocol.

Enantioselective epoxidation reactions of some chosen reactive alkenes by a chiral Mn(III) salen catalyst were performed in H2O employing H2O2 as oxidant and diethyltetradecylamine N-oxide (AOE-14) as surfactant. This procedure represents an environmentally benign protocol which leads to e.e. values ranging from good to excellent (up to 95%).

Asymmetric epoxidation of alkenes catalyzed by novel chiral porphyrin metal complexes

Novel chiral porphyrin ligands were synthesized from four different chiral aldehydes. In situ transition metal complexes of these novel chiral porphyrin ligands were found to catalyze asymmetric epoxidation reaction of styrene possessing various substituents. The chiral epoxides were formed in excellent yield and ee.

Stereochemical Communication within a Chiral Ion Pair Catalyst.

Ionic interactions are increasingly appreciated as a key, asymmetry-inducing factor in enantioselective catalytic transformations, including those involving Brønsted acid or base catalysis, phase-transfer catalysis, and related processes. However, a detailed understanding of these interactions is often lacking. Herein, we show how an enantiopure anion enforces a chiral conformation onto a catalytically relevant achiral cation. Specifically, we use vibrational circular dichroism (VCD) spectroscopy to monitor the transmission of stereochemical information from a chiral phosphate anion to a flexible manganese(III)-salen cation. We show that VCD can be used to study solvent effects and that the obtained chiroptical data directly and quantitatively correlate with the experimentally observed enantioselectivity in an asymmetric olefin epoxidation reaction.

Self-Supported Chiral Polymeric MnIII Salen Complexes as Highly Active and Recyclable Catalysts for Epoxidation of Nonfunctionalized Olefins.

A series of self-supported chiral polymeric MnIII N,N'-ethylenebis(salicylimine) (salen) complexes were synthesized through metalation of the corresponding salen ligands obtained by condensation of several bis/tris-aldehydes with (1R,2R)-1,2-diaminocyclohexane. Upon employment in the asymmetric epoxidation reaction of nonfunctionalized olefins, all complexes showed enhanced activity and enantioselectivity relative to the classical Jacobsen's monomeric salen complex. However, 1,3,5-triazole-based polymeric MnIII salen complex 7 was noticeably preferred over others owing to its ability to render higher enantioselectivity at the expense of lower catalyst loading. Furthermore, complex 7 was recycled and reused in eight recycling experiments with marginal loss in catalytic activity.

Tsutomu Katsuki (1946-2014).

Professor Tsutomu Katsuki died on October 30, 2014, at the age of 68. His research career focused largely on asymmetric oxidation using metal complexes as catalysts. Taking inspiration from nature, he was motivated to achieve high catalytic efficiency with complete stereo- and enantioselectivity, using molecular oxygen as oxidant. These goals continue to animate the field, with Katsuki’s contributions serving as examples to many. Katsuki was born on September 23, 1946 in Saga, Kyushu (Japan). He was an undergraduate and graduate student at Kyushu University, Fukuoka, receiving his PhD degree in 1976 under the direction of Professor Masaru Yamaguchi. During this time, he contributed to the development of the Yamaguchi esterification, which has become a standard reaction in the synthesis of macrolactones and highly functionalized esters. In 1979, Katsuki joined K. Barry Sharpless at Stanford University as a postdoctoral research associate, beginning his adventures in the use of metal catalysis for olefin oxidation with ruthenium tetraoxide as oxidizing agent. On January 18, 1980, he combined a tartrate diester, a titanium tetraalkoxide, tert-butylhydroperoxide, and a racemic allylic alcohol, and found that the reaction slowed down dramatically halfway through. A less discerning chemist might have dismissed this observation as a reaction gone wrong, but the careful and perceptive Katsuki realized its unusual nature. The result was the discovery of the asymmetric epoxidation (AE) reaction of allylic alcohols, the uniformly high enantioselectivity of which caused an immediate sensation in the chemical community, and led to the awarding of the 2001 Nobel Prize in Chemistry to Sharpless. Those days were recognized by Katsuki as the most exciting of his life. A myriad of synthetic applications of this reaction arose in the next few months, including the kinetic resolution of racemic secondary allylic alcohols and the synthesis of chiral natural products such as disparlure and sugar alcohols that had previously been unapproachable in enantioselective fashion.1 1 In 1981, Katsuki returned as a research associate to Kyushu University, where he rose to full professor in 1988. In 2011, he received the signal honor of being named University Professor at Kyushu, and in 2012 he joined the International Institute on Carbon-Neutral Energy Research (I2CNER), also located at Kyushu, as World Premier Institute Principal Investigator. Except for occasional work in total synthesis and the exploration of organic and metallic catalysts for other reactions, Katsuki focused much of his efforts on the asymmetric epoxidation of nonfunctionalized olefins. His laboratory was among the first to describe the type of chiral (salen)manganese(III) catalysts in common use today, bearing stereogenic centers in the diamine moiety and bulky and chiral substituents in the aromatic component. These systems provide high enantiomeric excess using several oxidants with substrates containing a wide variety of functional groups. Katsuki’s incisive mechanistic work on oxidations based on salen metal complexes was accompanied by his development of other enantioselective processes using these catalysts, including cyclopropanation, Baeyer–Villiger rearrangement, hetero-Diels–Alder cycloaddition, sulfoxidation, aziridination, and meso-diol desymmetrization reactions. One of Katsuki’s key goals was the development of oxidizing catalysts using air. In 2000, he published a seminal report of oxidative kinetic resolution of secondary alcohols with air at room temperature under visible-light irradiation in the presence of [(ON)Ru(salen)] complexes. Later, he extended the use of O2 to a series of important reactions such as coupling of 2-naphthols to enantiomeric binaphthols, dearomatization of 2-naphthols with construction of chiral quaternary stereocenters, and sulfide oxidation. Tsutomu Katsuki’s scholarly and scientific contributions are described in more than 300 papers that have had great impact in the chemistry community. He was honored with numerous awards and prizes, among them the Inoue Science Award (1996), the Synthetic Organic Chemistry Award, Japan (1998), the Chemical Society of Japan Award (2002), and the Ryoji Noyori Prize (2005). Katsuki’s personal contributions and influence were also profound to those who had the good fortune to know him. He considered himself first and foremost a teacher; his favorite way to start any scientific argument was “I am not sure”. This was invariably followed by a large amount of data and carefully reasoned personal remarks. The depth and breadth of knowledge of this extremely friendly and unassuming man was often astounding. While it is certainly true that we scientists stand on the shoulders of giants, few of those shoulders have belonged to more gentle and delightful pioneers than Tsutomu Katsuki.

Chiral electron deficient ruthenium helical coordination polymer as a catalyst for the epoxidation of substituted styrenes

An air and moisture stable ruthenium(III) formate complex [Ru(HCO2)Cl2]n has been synthesized and examined in the epoxidation of substituted styrenes. X-ray crystallographic data of this complex were determined and showed that the formate ligand coordinates to the ruthenium centers in a μ2–η2 fashion (syn, syn). Its asymmetric unit contains one Ru(III) ion together with the half of a formate ligand and one chloride anion, which are bridged between the metal centers, forming a 1-D chain coordination polymer. This electron deficient helical coordination polymer was employed in the epoxidation of para-fluorostyrene, affording the epoxide product in 92% yield. Natural chirality of this coordination polymer is applicable in asymmetric epoxidation reactions.

Asymmetric synthesis and biological evaluation of 1,3- and 1,4-disubstituted benzo-type lipoxin A4 analogues

The asymmetric synthesis of 1,3 and 1,4-disubstituted aromatic lipoxin A4 analogues has been accomplished. A total of eight analogues were synthesised in a convergent approach utilising Sharpless asymmetric epoxidation, asymmetric reduction and intermolecular Heck reactions. The set of analogues were assessed for their effect on the production of cytokines IL-12p40, IL-23, IL-6, IL-1β and TNFα. A positive inhibitory result was observed for the production of IL-6 and IL-1β.

Concise stereoselective total synthesis of (+)-muricatacin and (+)-epi-muricatacin

Efficient stereoselective total synthesis of (+)-muricatacin (1) and (+)-epi-muricatacin (8) was accomplished from commercially available chemical pent-4-ynoic acid via Shi's asymmetric epoxidation and Mitsunobu reaction as the key steps in 17.8% and 26.9% overall yields, respectively.

Remarkable Enhancement of Stability and Helix-sense Excess of Oligo(phenylene ethynylene) Foldamers Assisted by Linking with Achiral (Metallo)salen Tethers and Their Application to Asymmetric Catalysis

Abstract Two foldamer strands, which possess chiral amide pendants but imperfect helical handedness, were linked by an achiral (metallo)salen tether, leading to a remarkable enhancement of helical stability and helix-sense excess as a result of the intramolecular hydrogen-bond networks along the entire dimeric foldamer strand; the MnIII salen complexes catalyzed an asymmetric epoxidation reaction.

Asymmetric Epoxidation of Olefins with Homogeneous Chiral (Salen) Manganese (III) Complex

Optically active epoxides are known as versatile chiral building blocks in organic synthesis, and many efforts have been directed toward developing asymmetric epoxidation (AE) reaction of olefins. The first major breakthrough in AE using synthetic catalysts was realized by Katsuki and Sharpless in 1980, they achieved enantiomeric excesses (ee’s) greater than 90% in the titanium tartrate-based epoxidation of a variety of allylic alcohols. However, the substrates must bear specific functional groups to achieve the precoordination required for high enantioselectivity. In 1990 Jacobsen et al. and Katsuki et al. announced their independently developed systems for the catalytic AE of unfunctionalized olefins using chiral manganese (III) salen complexes. Since that time, the area of chiral manganese (III)- catalyzed AE has expanded greatly. In this review we will focus on the ligand development and the application of homogeneous chiral (salen) manganese (III)-promoted AE of olefins in recent years. Keywords: Asymmetric epoxidation, Chiral, Manganese, Salen, homogeneous, Ligand, Olefin.