Synthesis of N,N-Diethylbenzamides via a Nonclassical Mitsunobu Reaction

The use of the Mitsunobu reaction for the synthesis of N,N-diethylbenzamides affords ortho-, meta-, and para-substituted benzamides containing both electron-donating and electron-withdrawing groups. While the preparation of numerous functional groups has been efficiently demonstrated employing the Mitsunobu reaction, our methodology represents the first application of the Mitsunobu reaction for the construction of benzamides using benzoic acid and amine starting materials. Moreover, this synthetic transformation is believed to proceed via a nonclassical mechanism involving the existence of an acyloxyphosphonium ion.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Stereoselective Synthesis of Novel C-Disaccharides via Suzuki Cross-Coupling Reaction

Novel β-C-disaccharides containing a three carbon linkage using exo-glycal as the precursor were prepared stereoselectively. The synthesis was achieved by the tandem reactions of the stereoselective hydroboration of exo-glycal and Suzuki cross-coupling reaction with an iodovinyl sugar, and followed by hydrogenated deprotection under the catalysis of Pd（OH）2/C.     

Synthesis of azamacrocycles via a Mitsunobu reaction

Reaction of pernosylated diethylenetriamine and 2-substituted propane-1,3-diols in dry THF in the presence of triphenylphosphine and diisopropyl azodicarboxylate gives the corresponding protected 9-substituted 1,4,7-triazacyclodecanes. The Mitsunobu reaction was also used in the preparation of 3-substituted 1,5,9-triazacyclododecanes and macrocyclic pyridine derivatives.     

Synthesis of flavonoid 2-deoxyglucosides via the Mitsunobu reaction

The Mitsunobu reaction of flavonoids and 3,4,6-tri-O-acetyl-2-deoxy-d-glucopyranose or 3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranose is a very effective method for the stereoselective synthesis of flavonoid 2-deoxyglucosides. Since there is no C2 substituent on the sugar moieties, the observed α- or β-stereoselectivity was mainly controlled by the (acetyl or benzyl) protecting groups. Possible mechanistic insights are offered to explain the dual stereoselectivity.     

A Facile and Stereoselective Synthesis of Arylethers of Vicinal Bromohydrins by Mitsunobu Reaction

A straightforward, high yielding and stereoselective synthesis of 3,4-dihydro-4-aryloxy-3-bromo-2H-1-benzopyrans, compounds 8 and 9 by Mitsunobu coupling of the corresponding bromohydrins is reported.     

Mitsunobu反应研究进展

Mitsunobu反应可以在温和的中性条件下形成C—O,C—N,C—S,C—C等键,因此被广泛地应用于各类天然产物的全合成或化合物的官能团转化,是一个比较重要的反应.简要介绍了近年来Mitsunobu反应的研究进展.     

Stereoselective Synthesis of (Z)-1-Benzhydryl-4-cinnamylpiperazines via the Wittig Reaction

A synthetic method of producing (E)- and (Z)-isomers of 1-benzhydryl-4-cinnamylpiperazines in a specific ratio from corresponding benzhydrylpiperazine is described. Of the three compounds synthesized (5a–c), the ratio of E/Z-isomers remained around 15:85. The key intermediates, 1-benzhydryl-4-(2,2-dimethoxyethyl)piperazine derivatives (3a–c), were prepared by nucleophilic substitution reaction of benzhydrylpiperazines (2a–c) with chloroacetaldehyde dimethylacetal in good yield (up to 88%). Hydrolysis of 3a–c gave the corresponding aldehydes 4a–c, which when subjected to the Wittig reaction followed by column purification to afford 1a–c (E-isomers) and 6a–c (Z-isomers) in pure form. The isolated compounds were characterized by NMR and mass spectral analysis.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Stereoselective synthesis of styrene oxides via a Mitsunobu cyclodehydration

[reaction: see text] The Mitsunobu cyclodehydration of chiral phenethane-1,2-diols (4), readily accessed from the styrene derivative (5), has been demonstrated to provide the corresponding styrene oxides (2) with high levels of stereoretention (up to 99%). Optimized reaction conditions are described, from which the combination of tricyclohexylphosphine (Chx(3)P) and diisopropylazodicarboxylate (DIAD) in THF and R = EWG provides the best results.     

Stereoselective Synthesis of Highly Substituted Tetrahydrofurans through Diverted Carbene OH Insertion Reaction

Copper‐ or rhodium‐catalyzed reactions of diazocarbonyl compounds with β‐hydroxyketones give highly substituted tetrahydrofurans with excellent diastereoselectivity. Under mild conditions, the single‐step process starts as a carbene O? H insertion reaction, but is diverted by an intramolecular aldol reaction.     

Synthesis of New 4-Thiazolidinylphosphonates via Stereoselective Pudovik Reaction

Diastereomeric pure phosphite anions 2 adds to the C=N bond of 3-thiazolines 3 to give the corresponding derivatives 4 of the pharmacological active 4-thiazolidinylphosphonates 1 via Pudovik reaction.     

Synthesis and Structural Analysis of Organic Cyclic Polyselenides Obtained from the Reaction of a Bissilylcarbenoid with Selenium

The synthesis and isolation of the first examples of a tetraselenolane and a hexaselenepane, obtained from the reaction of a bissilylcarbenoid (R^Si₂CBrLi; R^Si=SiMePh₂) with elemental selenium, is reported. The molecular structures of these cyclic polyselenides were determined using single-crystal X-ray diffraction analysis. The selective synthesis of these polyselenides was achieved by controlling the reaction temperature. Stoichiometric deselenation of the hexaselenepane with triphenylphosphine afforded the corresponding tetraselenolane in quantitative yield. Further deselenation of the tetraselenolane with excess triphenylphosphine did not furnish the expected selenoketone but the diselenirane, as confirmed by spectroscopic analysis.     

The Mitsunobu Reaction: Origin,Mechanism, Improvements,and Applications

The Mitsunobu reaction is a widely used and versatile method for the dehydrative oxidation–reduction condensation of an acid/pronucleophile usually with a primary or secondary alcohol that requires the combination of a reducing phosphine reagent together with an oxidizing azo reagent. The utility of this reaction stems from the fact that it is generally highly stereoselective and occurs with inversion of the stereochemical configuration of the alcohol starting material. Furthermore, as carboxylic acids, phenols, imides, sulfonamides, and other compounds can be used as the acid/pronucleophile, this reaction is useful for the preparation of a wide variety of functional groups. This Focus Review of the Mitsunobu reaction summarizes its origins, the current understanding of its mechanism, and recent improvements and applications.     

A Nazarov-Ene Tandem Reaction for the Stereoselective Construction of Spiro Compounds

The different reactivity of trienones under Lewis and Brønsted acids catalysis was investigated, resulting in distinct cyclization products and carbon backbones that originated either from a conjugate Prins cyclization or an interrupted Nazarov cyclization. In particular, an unprecedented Nazarov cyclization tandem reaction is presented, terminating the oxyallyl cation by an ene-type reaction, and leading stereoselectively to bicyclic spiro compounds. The terminal olefin of this motif represents a useful handle for further functionalization, making it a strategic intermediate in total syntheses. The tandem Nazarov/ene cyclization was shown to be preferred over a Nazarov/[3+2] tandem reaction for all our substrates, independent of chain length. Deuteration studies further support the mechanistic hypothesis of the terminating ene reaction.     

Intramolecular Nicholas Reaction Enables the Stereoselective Synthesis of Strained Cyclooctynes

Cyclic products can be obtained through the intramolecular version of the Nicholas reaction, which requires having the nucleophile connected to the alkyne unit. Here, we report the synthesis of 1-oxa-3-cyclooctynes starting from commercially available (1R,3S)-camphoric acid. The strategy is based on the initial preparation of propargylic alcohols, complexation of the triple bond with Co₂(CO)₈, and treatment with BF₃·Et₂O to induce an intramolecular Nicholas reaction with the free hydroxyl group as nucleophile. Finally, oxidative deprotection of the alkyne afforded the cyclooctynes in good yields. Notably, large-sized R substituents at the chiral center connected to the O atom were oriented in such a way that steric interactions were minimized in the cyclization, allowing the formation of cyclooctynes exclusively with (R) configuration, in good agreement with theoretical predictions. Moreover, preliminary studies demonstrated that these cyclooctynes were reactive in the presence of azides yielding substituted triazoles.     

微波促进立体选择性合成烯丙酸酯类高碳糖衍生物

在微波促进下, 利用酮糖(1)及糖酸内酯(4)与叶立德(2, Ph₃PCHCOOEt)的Wittig反应, 立体选择性地合成了糖基烯丙酸酯类化合物(3和5), 反应效率显著提高, 反应时间由原来的20 h缩短为10 min; 并且研究了不同反应溶剂对反应立体选择性的影响. 提供了一种高效、 简便合成含有烯丙酸酯类高碳糖衍生物的方法.     

利用Mitsunobu反应合成川芎嗪衍生物

以川芎嗪为起始原料,利用Mitsunobu反应合成了三个3,5,6.三甲基吡嗪.2-基-甲氧基苯甲醛衍生物,收率87%～92%.其结构经1H NMR,13C NMR和ESI-MS表征.     

A Convenient Synthesis of Novel Glycosyl Azetidines Under Mitsunobu Reaction Conditions

Abstract

A facile, simple, and high-yielding protocol for synthesis of novel glycosyl azetidines was developed from glycosyl β-amino alcohols via intramolecular cyclization under Mitsunobu reaction conditions.     

Efficient Synthesis of Pyridylacrylonitriles via the Heck Reaction

A new synthetic pathway to pyridylacrylonitriles has been developed based on a palladium‐catalyzed Heck reaction. The optimized process and the preparation of related functionalized pyridylacrylonitriles are discussed.     

Mitsunobu Reaction: A Powerful Tool for the Synthesis of Natural Products: A Review

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.