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Stereoselective synthesis has been emerging as a resourceful tool because it enables the obtaining of compounds with biological interest and high enantiomeric purity. Flavonoids are natural products with several biological activities. Owing to their biological potential and aiming to achieve enantiomerically pure forms, several methodologies of stereoselective synthesis have been implemented. Those approaches encompass stereoselective chalcone epoxidation, Sharpless asymmetric dihydroxylation, Mitsunobu reaction, and the cycloaddition of 1,4-benzoquinone. Chiral auxiliaries, organo-, organometallic, and biocatalysis, as well as the chiral pool approach were also employed with the goal of obtaining chiral bioactive flavonoids with a high enantiomeric ratio. Additionally, the employment of the Diels–Alder reaction based on the stereodivergent reaction on a racemic mixture strategy or using catalyst complexes to synthesise pure enantiomers of flavonoids was reported. Furthermore, biomimetic pathways displayed another approach as illustrated by the asymmetric coupling of 2-hydroxychalcones driven by visible light. Recently, an asymmetric transfer hydrogen-dynamic kinetic resolution was also applied to synthesise (R,R)-cis-alcohols which, in turn, would be used as building blocks for the stereoselective synthesis of flavonoids. [ABSTRACT FROM AUTHOR]

Natural and synthetic coumarins are often considered privileged scaffolds for obtaining pharmacological agents with hypoglycemic activity. Chemical modification of coumarins often leads to antidiabetic agents with greater efficacy. In the present work, twenty monoterpene-substituted 7-hydroxycoumarins were synthesized. A new approach using the Mitsunobu reaction was shown to be effective for the synthesis of target compounds. All of the synthesized compounds were evaluated in an oral glucose tolerance test, and two of them containing geranyl and (-)-myrtenyl substituents showed in vivo hypoglycemic action. A possible mechanism of action of these compounds may include inhibition of DPP IV, which was proved in an in vitro test. [ABSTRACT FROM AUTHOR]

The diversity of polyhydroxylated indolizidine (PI) iminosugars is ever-expanding due to the wide range of methods developed and substrate choice during synthesis. This study used an HWE precursor derived from d -glucose to extend the chain length at the C1 position. A double reductive amination and dihydroxylation of the resulting olefin, followed by intramolecular cyclization, enabled the successful synthesis of a new PI. In addition, the precursor intermediate for Mitsunobu reaction was utilized in synthesis of a new iminononulol. [Display omitted] • This study describes a methodology for synthesizing a new polyhydroxylated indolizidine iminosugar from an HWE precursor. • The methodology also enabled the synthesis of a new iminononulol. • The enone generated from the HWE reaction can be used in 1,4-Michael addition reactions to increase the diversity of polyhydroxylated indolizidines. [ABSTRACT FROM AUTHOR]

A simple and rapid access to fluorinated dithioesters was developed by a one-pot sequence corresponding to a Grignard reaction—Mitsunobu type substitution. These activated dithioesters have shown excellent reactivity in an aminolysis reaction from simple or more complex primary amines such as cinchona alkaloids. A stoichiometric amount of amine was sufficient to prepare various thioamides, including a 4-styrenylthioamide cinchonidine monomer, under environmentally friendly conditions, at room temperature, and in a very short time.

The Mitsunobu reaction plays a vital part in organic chemistry due to its wide synthetic applications. It is considered as a significant reaction for the interconversion of one functional group (alcohol) to another (ester) in the presence of oxidizing agents (azodicarboxylates) and reducing agents (phosphines). It is a renowned stereoselective reaction which inverts the stereochemical configuration of end products. One of the most important applications of the Mitsunobu reaction is its role in the synthesis of natural products. This review article will focus on the contribution of the Mitsunobu reaction towards the total synthesis of natural products, highlighting their biological potential during recent years. [ABSTRACT FROM AUTHOR]

The Mitsunobu reaction of tris(2-hydroxyphenyl)phosphine oxide with 3-butyn-1-ol has afforded bis[2-(3′′-butynyloxy)phenyl](2′-hydroxyphenyl)phosphine oxide, which has been converted into the corresponding triazole via click reaction with PhN3. Asymmetric tripodal ligand containing three 1,2,3-triazole groups in the molecule has been prepared from this triazole via the reaction with propargyl bromide and PhN3. Structure of the ligand has been elucidated by means of single-crystal X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Novel di- and tetra-substituted calix[4]arene derivatives bearing diacetylene moieties at the lower rim of macrocycle were synthesized via the Mitsunobu and Williamson reactions. The dealkylation of diacetylene moieties of calix[4]arene was for the first time discovered in the DMSO—hydrazine hydrate system. An important role in the dealkylation of diacetylene moieties is played by neighboring unsubstituted OH groups at the macrocycle. Blocking of OH groups with butyl substituents and elongation of the linker between the butadiynyl fragments and the macrocyclic platform significantly reduce the affinity of macrocycle to reductive cleavage. The unique reactivity of calix[4]arene in its reaction with hydrazine hydrate was demonstrated in comparison with a model conjugate of diacetylene with 4-tert-butylphenol. The reductive cleavage may proceed via the formation of pyrazole derivative of calix[4]arene. Pyrazole derivatives were the most reactive ones in the reaction with hydrazine hydrate among the studied isostructural calixarenes containing an active α-arylmethyleneoxy moiety. Results of performed quantum chemical calculations allowed us to propose a scheme for the reductive cleavage of oxymethylene derivatives of pyrazole with hydrazine hydrate. [ABSTRACT FROM AUTHOR]

To test the RInChI algorithm, the RInChI and the RInChI keys (Long-RInChIKey, Short-RInChIKey and Web-RInChIKey) for the entire reaction part of the database were calculated. Keywords: Cheminformatics; InChI; integrating reaction data; reaction databases; RInChI; SAVI; SPRESI EN Cheminformatics InChI integrating reaction data reaction databases RInChI SAVI SPRESI 643 655 13 08/09/22 20220601 NES 220601 Introduction This is an exciting time in the computational analysis of reactions. Reaction duplicate checks in SPRESI by InfoChem InfoChem GmbH [[18]], Munich, Germany, publishes the chemical database SPRESI containing 5.8 million molecules abstracted from literature, nearly 6.6 million reactions, 700 000 references and 164 000 patents with the major focus on organic chemistry covering the years 1974-2014 [[5]]. Cheminformatics, SAVI, SPRESI, InChI, integrating reaction data, reaction databases, RInChI. [Extracted from the article]

S-(−)-trans-Verbenol (1) and its antipode, R-(+)-trans-verbenol (1′) have been confirmed as the critical pheromone components of bark beetles. Synthesis of these two active secondary alcohols (1 and 1′) from commercially available starting materials S-α-pinene and R-α-pinene was reported. The key steps were mainly depended on the effective SN2 stereo-inversion of the hydroxy group of sterically hindered alcohols (3 and 3′), using Mitsunobu reaction or hydrolysis of mesylate ester, alternatively. Our results provide a new and stereo-selectivity way to obtain optically active insect pheromones. [ABSTRACT FROM AUTHOR]

A catalytic enantioselective β‐O‐elimination reaction is reported in the form of a zirconium‐catalyzed asymmetric opening of meso‐ketene acetals. Furthermore, a regiodivergent β‐O‐elimination is demonstrated. The reaction proceeds under mild conditions, at low catalyst loadings, and produces chiral monoprotected cis‐1,2‐diols in good yield and enantiomeric excess. The combination with a Mitsunobu reaction or a one‐pot hydroboration/Suzuki reaction sequence then gives access to additional diol and aminoalcohol building blocks. A stereochemical analysis supported by DFT calculations reveals that a high selectivity in the hydrozirconation step is also important for achieving high enantioselectivity, although it does not constitute the asymmetric step. This insight is crucial for the future development of related asymmetric β‐elimination reactions. [ABSTRACT FROM AUTHOR]

The glycosylation of protecting‐group‐free pyranoses with flavonoids to generate flavonoid O‐glycosides under Mitsunobu conditions was reported. The methodology allows to prepare a wide range of natural 7‐flavonoid O‐glycosides and their derivatives from commercially available chemicals in good to excellent yields with exclusive 1,2‐trans‐stereoselectivity regardless the anomeric configuration of employed pyranoses. The highly regioselective glycosylation was also achieved among different types of hydroxyl groups on the glycosyl acceptors. [ABSTRACT FROM AUTHOR]

In the present study, we continue our work related to the synthesis of 1,8-naphthalimide and carborane conjugates and the investigation of their anticancer activity and DNA-binding ability. For this purpose, a series of 4-carboranyl-1,8-naphthalimide derivatives, mitonafide, and pinafide analogs were synthesized using click chemistry, reductive amination, amidation, and Mitsunobu reactions. The calf thymus DNA (ct-DNA)-binding properties of the synthesized compounds were investigated by circular dichroism (CD), UV–vis spectroscopy, and thermal denaturation experiments. Conjugates 54–61 interacted very strongly with ct-DNA (∆Tm = 7.67–12.33 °C), suggesting their intercalation with DNA. They were also investigated for their in vitro effects on cytotoxicity, cell migration, cell death, cell cycle, and production of reactive oxygen species (ROS) in a HepG2 cancer cell line as well as inhibition of topoisomerase IIα activity (Topo II). The cytotoxicity of these eight conjugates was in the range of 3.12–30.87 µM, with the lowest IC50 value determined for compound 57. The analyses showed that most of the conjugates could induce cell cycle arrest in the G0/G1 phase, inhibit cell migration, and promote apoptosis. Two conjugates, namely 60 and 61, induced ROS production, which was proven by the increased level of 2′-deoxy-8-oxoguanosine in DNA. They were specifically located in lysosomes, and because of their excellent fluorescent properties, they could be easily detected within the cells. They were also found to be weak Topo II inhibitors. [ABSTRACT FROM AUTHOR]

A series of 2′‐deoxy carbocyclic nucleosides characterized by various 6′‐substitutions were synthesized and evaluated for their antiviral activities against three viruses, including hepatitis B virus (HBV), hepatitis C virus, and influenza virus. The in vitro antiviral assays indicated that these nucleosides only showed inhibitory activities against HBV, and the substituted groups at the 6′ position significantly affected the activity. Among them, the guanosine analog 2b bearing a 6′‐α‐hydroxyl methyl group was the most potent compound with an EC50 value of 80 nM. The present study provided useful information for the discovery of antiviral carbocyclic nucleosides. [ABSTRACT FROM AUTHOR]

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)2(acac), was attested by 31P NMR, which presented a doublet in the range of δ = 120 ppm, with a 1J(103Rh-31P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm−1 and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene. [ABSTRACT FROM AUTHOR]

α‐Allenol is a versatile synthon in organic synthesis. The catalytic asymmetric synthesis of α‐allenols from readily available starting materials remains a prominent challenge, especially when simultaneous control over axial and central chirality is required. Herein, we describe the Cr‐catalyzed enantioconvergent allenylation of aldehydes with racemic propargyl halides to rapidly access a wide range of chiral α‐allenols with adjacent axial and central chiralities. This method features excellent regio‐, diastereo‐ and enantioselectivity control with broad substrate scope, and provides facile access to all four stereoisomers when allied with a Mitsunobu reaction. Preliminary mechanistic studies support radical‐based reaction pathways. The synthetic utility is demonstrated by the application in late‐stage functionalization and the formal total synthesis of (+)‐varitriol. [ABSTRACT FROM AUTHOR]

It was recently reported that a (2-hydroxybenzyl)phosphine oxide (2-HOBPO) can serve as a phosphorus-centered catalyst for the stereo-invertive coupling of aliphatic alcohols and acidic pronucleophiles (akin to a Mitsunobu reaction, but without additional reagents). Herein, we report an improved synthesis, which provides direct access to systematically varied 2-HOBPOs in a single step from commercially available precursors (salicylaldehydes and secondary phosphines). The efficiency and generality of the synthetic method enabled limited structure–activity relationship (SAR) studies, from which it was determined that substituents on both the phenolic and phosphine oxide portions can exert significant influence on the turnover frequency (TOF) of each catalyst. Importantly, for all catalytically active 2-HOBPOs examined, the molecularity of catalyst in the rate law of the alcohol coupling was determined to be <1. Thus, for high catalyst loadings, differences in catalytic activity between 2-HOBPOs appear to be dominated by differences in catalytic auto-inhibition, while for low catalyst loadings, differences are attributed to inherent differences in the energetic span of the catalytic cycle, ignoring off-cycle species, in good agreement with density functional theory (DFT) modeling at the ωB97X-D/6-311G(d,p) level. [ABSTRACT FROM AUTHOR]

Phosphine‐mediated deoxygenative nucleophilic substitutions, such as the Mitsunobu reaction, are of great importance in organic synthesis. However, the conventional protocols require stoichiometric oxidants to trigger the formation of the oxyphosphonium intermediates for the subsequent nucleophilic additions. Through dual catalysis of photoredox and cobaloxime, we realized a radical strategy for the catalytic formation of acyloxyphosphonium ions that enables direct amidation. The deoxygenative protocol exhibits a broad scope and has been used in the late‐stage amidation of drug molecules. In addition to batch reactions, a continuous‐flow reactor was developed, enabling rapid peptide synthesis on gram scale. The successful assembly of a tetrapeptide on the solid support further demonstrated the versatility of this photocatalytic system. Moreover, experimental and computational studies are consistent with the hypothesis of acyloxyphosphonium ions being formed as the key intermediates. [ABSTRACT FROM AUTHOR]

Routes are reported for the synthesis of both (1 R)- and (1 S)- tert -butyl-(4-oxocyclopent-2-en-1-yl)carbamate 2. Featuring Mitsunobu reactions with di- tert -butyl iminodicarbonate, both syntheses begin from (S)-4-[(tert -butyldimethylsilyl)oxy]cyclopent-2-en-1-one (3) and take advantage of the 1,4-cyclopentenyl dioxygenation pattern of this optically active starting material. Thus both (−)- and (+)- 2 have been accessed from 3 in an enantiodivergent manner in 11% and 10% overall yield over five and seven reaction steps, respectively. [ABSTRACT FROM AUTHOR]

All possible stereoisomers of cis- and trans-2-fluorocyclopentan-1-ols were obtained by kinetically controlled deracemization in the presence of lipases in organic media. High enantioselectivities and good yields of stereomers were obtained for all substrates. Optically pure 1,2-fluorocyclopentan-1-ols were converted to 2- fluoro-cyclopentan-1-amines using the Mitsunobu reaction. The absolute configurations were determined using the Kazlauskas rule and chemical correlation. The interaction of substrates with enzymes has considered using Koshland induced fit theory. [ABSTRACT FROM AUTHOR]

Conversion of alcohols to carbonate was observed under the mild conditions of Mitsunobu reaction in presence of silver salt. An investigation is undertaken to explore this unexpected observation, where the presence of DEAD (Diethylazodicarboxylate) and silver salt is essential, while Ph3P is not required. The formation of carbonate is stereospecific, follows with retention of configuration; iso‐propyl carbonate is formed when DIPAD (Diisopropylazodicarboxylate) is used. The method is extended for several examples of alcohols, while it doesn't works for phenols. [ABSTRACT FROM AUTHOR]

An efficient total synthesis of the naturally occurring anti-inflammatory and antitumour 8-O-4′-neolignans, surinamensinols A and B, has been accomplished from commercially available allyl alcohol and (S)-ethyl lactate. The synthetic sequence involves a palladium-catalysed Suzuki–Miyaura cross-coupling reaction followed by a chiral Mitsunobu­ reaction as the key steps. This is the first report of the simultaneous stereoselective total synthesis of surinamensinols A and B through a single approach involving only six steps.

Abstract Two series of N-methyliminodiacetic acid (MIDA) boronates were prepared and their mesomorphic properties were investigated. MIDA-substituted benzoic acid esters were synthesized via the Mitsunobu reaction. The second series of MIDA benzyl ether derivatives was prepared via Williamson etherification and subsequent borylation. Both series exhibit smectic A (SmA) phases. In the case of MIDA boronate esters, a substitution with perfluorinated side chains led to increased transition temperatures and broadening of the SmA phases. The phase geometries of the mesophases were determined by X-ray diffraction. Quantum-chemical calculations provided further insight into the packing model.

Tetrahydropyrenophorol, an interesting macrodiolide, was isolated from the plant Fagonia cretica. The total synthesis of (–)-1-tetrahydropyrenophorol was achieved in an elegant and linear manner from readily an accessible racemic epoxide. The archetypal reactions include regioselective opening of the epoxide, Sharpless asymmetric dihydroxylation, and Mitsunobu cyclodimerization to construct the requisite 16-membered bis-lactone. The synthetic approach demonstrated here is very simple and could be used for the syntheses of related compounds in an economic and highly stereoselective way.

With unique chemical reactivity, α‐oxoketene S,S‐ and N,S‐acetals have attracted enormous attention in the past decades, whereas limited reports exist for their synthesis via eco‐compatible protocols. Herein, we developed a one‐pot protocol for symmetrical and unsymmetrical α‐oxoketene S,S‐/N,S‐acetals through chemoselective alkylation of α‐enolic dithioesters using Mitsunobu chemistry at room temperature. The operationally simple and user‐friendly mild protocol tolerates a wide range of alcohols and α‐enolic dithioesters/β‐ketothioamides. Short reaction time, good yields, highly selective C−S functionalization, and E/Z‐stereoselectivity are imperative characteristics of this strategy. [ABSTRACT FROM AUTHOR]

A polystyrene-supported version of the Denton catalyst for redox-neutral Mitsunobu reactions, (2-hydroxybenzyl)diphenylphosphine oxide, has been developed and used in catalytic inversion of enantiopure secondary alcohols (21 examples, up to 97% yield and 98% ee) with 2-nitrobenzoic and 2,4-dinitrobenzoic acids. The use in the reaction of alternative pronucleophiles has also been explored (8 successful and 3 unsuccessful examples). The functional resin shows high recyclability (10 cycles, 30 days operation) and can be re-activated by simple treatment with butylamine with further extension of its useful life. [ABSTRACT FROM AUTHOR]

The first total synthesis of anti-inflammatory cyclic peptide fanlizhicyclopeptide B based on the Mitsunobu reaction is reported. The pre-made Fmoc-Tyr-OAllyl building block was coupled to the Wang resin via the Mitsunobu reaction catalyzed by triphenylphosphine and diethyl azodicarboxylate. After the remaining amino acids were assembled, macrocyclization was realized on solid support. Finally, the crude product was cleaved from resin and then purified by preparative reverse-phase high-performance liquid chromatography (RP-HPLC) to provide the pure target fanlizhicyclopeptide B. [ABSTRACT FROM AUTHOR]

Cellulose esters of hydroxycinnamic acids, namely ferulic‐, p‐coumaric‐, and caffeic acid, are synthesized by Mitsunobu esterification applying triphenylphosphine and diisopropyl azodicarboxylate in N,N‐dimethylacetamide/LiCl. The reaction is found to be highly selective and took place at primary hydroxyl groups at position 6 of cellulose without undesired conversion of double bonds and phenolic hydroxyl groups. Molecular structure characterization is performed by FTIR‐ and NMR spectroscopy. The products are soluble in dimethyl sulfoxide and possessed degree of substitution (DS) values of up to 0.5. DS values are determined by two independent methods, namely 1H NMR spectroscopy of peracetylated derivatives and UV spectroscopy of extracted ferulic acid. The synthesis of cellulose hydroxycinnamates is very important to design lignocellulosic model systems and antioxidative bioinspired materials. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the issue on topics including Synthesis of Donor-Acceptor π-Conjugated Macrocycles by Post-Functionalization, Five Novel Pterocarpan Derivatives from Sophora flavescens, and Intra-Ring Bridging: A Strategy for Molecular Design of Highly Energetic Nitramines.

A deoxyamination methodology of activated and unactivated alcohols is presented. The reaction is mediated by phosphonium intermediates generated in situ from N‐haloimides and triphenylphosphine. The protocol allows for the synthesis of phthalimide and amine derivatives in moderate to good yields at room temperature. A series of NMR experiments have provided insight into the reactive intermediates involved and the mechanism of this deoxyamination reaction. [ABSTRACT FROM AUTHOR]

In the current research on 13C-labeled compounds breath test of liver function, methacetin-methoxy-13C is the most potential substrate. To study a new method for synthesis methacetin-methoxy-13C, methanol-13C was used as the labeled material, methacetin-methoxy-13C was synthesized efficiently through Mitsunobu reaction and functional group modification. The synthesis yield was 63% and the chemical purity was above 99%. At the same time, this method was used to synthesize 4-methoxybenzoic acid-methoxy-13C with methanol-13C as the labeled material. The synthesis yield was 67% and the chemical purity was above 99%. The new scheme for the synthesis of methacetin-methoxy-13C with Mitsunobu reaction as the key reaction could provide a basis for the study of liver function by breath test.

The Mitsunobu reaction plays a vital part in organic chemistry due to its wide synthetic applications. It is considered as a significant reaction for the interconversion of one functional group (alcohol) to another (ester) in the presence of oxidizing agents (azodicarboxylates) and reducing agents (phosphines). It is a renowned stereoselective reaction which inverts the stereochemical configuration of end products. One of the most important applications of the Mitsunobu reaction is its role in the synthesis of natural products. This review article will focus on the contribution of the Mitsunobu reaction towards the total synthesis of natural products, highlighting their biological potential during recent years.

The N-alkylation of diketopyrrolopyrroles (DPPs) represents a fundamental step to ensure solubility and further processability. Commonly used nucleophilic substitution in halogenated derivatives is replaced in this work by the Mitsunobu reaction affording unprecedented DPPs with α-branched and chiral chains. [ABSTRACT FROM AUTHOR]

A concise enantioselective total synthesis of the neoclerodane diterpene (−)‐salvinorin A is reported. The stereogenic center at C‐12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two intramolecular Diels‐Alder reactions were applied to generate the tricyclic core. A chemoselective Mitsunobu inversion of a syn 1,2‐diol allowed for further streamlining of the original reaction sequence by two steps. Overall, (−)‐salvinorin A was synthesized in only 16 steps starting from 3‐furaldehyde with 1.4 % total yield. Furthermore, an alternative intramolecular Diels‐Alder strategy employing a 2‐bromo‐1,3‐diene moiety was investigated. [ABSTRACT FROM AUTHOR]

To find a potent α-glucosidase inhibitor, 24 tyrosol derivatives with different substituents located at the meta, ortho, or para position of the phenyl group have been synthesised via the Mitsunobu reaction, characterised by 1H NMR, 13C NMR, ESI-MS and IR and evaluated for inhibition. The derivatives possessed varying degrees of in vitro inhibitory activity against α-glucosidase and a relationship between the structure and activity was subsequently established for all compounds. Two of these compounds with substituents at the para position showed significant inhibitory effects surpassing that of the control standard acarbose. Molecular docking studies performed to better understand the binding interactions between the enzyme and the two most active compounds showed substantial binding within the active site of α-glucosidase. Taken together, these results indicate that the position of the substituent plays a crucial role in this inhibition and may facilitate the development of new α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

A synthesis of novel fluorescent 2-azolyl-6-piperidinylpurine derivatives was designed. Azolyl substituent at purine C-2 atom was introduced via nucleophilic aromatic substitution or in the case of tetrazolyl and 1,2,3-triazolyl substituents via a ring formation on a preinstalled amine or azide moiety, respectively. The obtained purine intermediates were functionalized at N-9 position using Mitsunobu reaction conditions to achieve amorphous compounds, which form thin-layer films of good quality. The synthesized push-pull systems exhibited fluorescence with emission in range of 360–400 nm and quantum yields up to 66% in CH2Cl2 solution and up to 45% in the thin-layer film. [ABSTRACT FROM AUTHOR]

In recent past, dialkyl azodicarboxylates have been embraced as versatile reagents in synthetic strategies other than Mitsunobu reactions. These azo compounds have been utilized as an oxidant or dehydrogenating reagent in oxidative transformations, such as cross dehydrogenative coupling, oxidative Ugi‐type reaction, dehydrogenation etc. Moreover, they have been utilized in different types of bond construction like C‐Heteroatom (C‐Het) and S−N bond. Very recently, these azo compounds have also been explored in photochemical reactions. Such types of reported reactions and their reaction pathways are presented here in this minireview, which manifested the oxidative abilities and advantageous features of dialkyl azodicarboxylates. [ABSTRACT FROM AUTHOR]

The article presents a study of the effectiveness of Transformer Neural Networks (TNN) in the unsupervised learning of organic chemical reactions. Topics discussed include the significance of the model to downstream applications requiring atom-mapping and chemical reaction rules, benefit of using symbolic representations and the means to autonomously learn from chemical data, and the role of the attention matrix construction for a selected layer and head in the attention-guided algorithm.

Our recent studies on the development of new synthetic methods using molecular oxygen (O2), which is an environmentally friendly oxidant, are described in this Account. The character of O2 as an electron acceptor can be utilized for activation of simple organic molecules to generate reactive species. Such reactive species are applicable to advanced molecular transformation, such as C–C and C–X (X = heteroatom) bond formation, functionalization of inactivated C(sp3)–H, and catalytic Mitsunobu reaction, by avoiding direct quenching of the reactive species by O2. 1 Introduction 2 Reactions with Iron Catalysts and Oxygen 2.1 Reactions Using Redox Hydration of Alkenes 2.2 Reactions Using Oxidation of Heteroatoms 3 Reactions with tert -Butyl Nitrite and Oxygen 4 Conclusion [ABSTRACT FROM AUTHOR]

It was recently reported that a (2-hydroxybenzyl)phosphine oxide (2-HOBPO) can serve as a phosphorus-centered catalyst for the stereo-invertive coupling of aliphatic alcohols and acidic pronucleophiles (akin to a Mitsunobu reaction, but without additional reagents). Herein, we report an improved synthesis, which provides direct access to systematically varied 2-HOBPOs in a single step from commercially available precursors (salicylaldehydes and secondary phosphines). The efficiency and generality of the synthetic method enabled limited structure–activity relationship (SAR) studies, from which it was determined that substituents on both the phenolic and phosphine oxide portions can exert significant influence on the turnover frequency (TOF) of each catalyst. Importantly, for all catalytically active 2-HOBPOs examined, the molecularity of catalyst in the rate law of the alcohol coupling was determined to be

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)2(acac), was attested by 31P NMR, which presented a doublet in the range of δ = 120 ppm, with a 1J(103Rh-31P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm−1 and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.

We have developed a two‐step protocol for iodotrimethylsilane‐mediated deoxy‐functionalization of primary and secondary alcohols to afford products containing a C−N, C−S, or C−O bond. In the first step the alcohol undergoes iodination with iodotrimethylsilane, and in the second, the iodine atom is replaced by a N, S, or O nucleophile. Compared with traditional Mitsunobu reaction, non‐acidic pre‐nucleophiles can be used, and the reaction proceeds with retention of configuration. This operationally simple, highly efficient protocol can be used for some natural products and small‐molecule drugs containing hydroxy‐group. [ABSTRACT FROM AUTHOR]

A convergent approach for the synthesis of the two key fragments (C1-C4 and C5-C14) of cytospolide D is described. Key transformations include MacMillan's crossed aldol, Sharpless asymmetric dihydroxylation (AD) and Mitsunobu inversion reactions. [ABSTRACT FROM AUTHOR]

The coupling of a nucleobase is a key step in the synthesis of most nucleoside analogs, e.g. carbocyclic nucleosides, isonucleosides and acyclic nucleosides. The synthetic strategies for nucleosides based on Nglycosylation are not applied when the nucleobase is not linked to the anomeric center. Thus, other methods have been employed, mainly those based on the alkylation of nucleobases. The Mitsunobu reaction, in which a hydroxy group is replaced by a nucleophile, has also been extensively applied, generating a diversity of molecules, including pharmaceuticals and their precursors. In this review the usefulness of this reaction for the coupling of nucleobases to non-anomeric positions of sugars, carbasugars and other homocyclic and linear structures is highlighted and discussed, covering purines and pyrimidines as pronucleophiles. [ABSTRACT FROM AUTHOR]

Mitsunobu reactions of cannabidiol (CBD) as the acid component and primary alcohols, for example benzyl, allyl, propargyl and methyl glycolate as the alcohol component gave the corresponding bis-alkylated CBD derivatives which were also obtained by alkylating CBD with the corresponding alkyl bromides. Alkylation of CBD with methyl bromoacetate followed by saponification of the two ester moieties and neutralization of the di-carboxylic acid afforded a water-soluble CBD bis-acetate bis-potassium salt. [ABSTRACT FROM AUTHOR]

Enantioselective synthesis of the neurokinin 1 receptor antagonist (+)-L-733,060 has been achieved using Jacobsen's hydrolytic kinetic resolution strategy. Intermediate tert-butyl (2S,3S)-3-hydroxy-2-phenylpiperidine-1-carboxylate has been synthesized with an overall yield of 10.25% and more than 98% ee via sequential reactions starting from cinnamyl alcohol and using Grubbs metathesis in the final stage. [ABSTRACT FROM AUTHOR]

The Mitsunobu reaction basically consists in the conversion of an alcohol into an ester under inversion of configuration, employing a carboxylic acid and a pair of two auxiliary reagents, mostly triphenylphosphine and a dialkyl azodicarboxylate. This reaction has been frequently used in carbohydrate chemistry for the modification of sugar hydroxy groups. Modification at the anomeric position, leading mainly to anomeric esters or glycosides, is of particular importance in the glycosciences. Therefore, this review focuses on the use of the Mitsunobu reaction for modifications of sugar hemiacetals. Strikingly, unprotected sugars can often be converted regioselectively at the anomeric center, whereas in other cases, the other hydroxy groups in reducing sugars have to be protected to achieve good results in the Mitsunobu procedure. We have reviewed on the one hand the literature on anomeric esterification, including glycosyl phosphates, and on the other hand glycoside synthesis, including S- and N-glycosides. The mechanistic details of the Mitsunobu reaction are discussed as well as this is important to explain and predict the stereoselectivity of anomeric modifications under Mitsunobu conditions. Though the Mitsunobu reaction is often not the first choice for the anomeric modification of carbohydrates, this review shows the high value of the reaction in many different circumstances.