Nonstabilized Ylides Research Articles

Optimal Oriented External Electric Fields to Trigger a Barrierless Oxaphosphetane Ring Opening Step of the Wittig Reaction.

The Wittig reaction is one of the most important processes in organic chemistry for the asymmetric synthesis of olefinic compounds. In view of the increasingly acknowledged potentiality of the electric fields in promoting reactions, here we will consider the effect of the oriented external electric field (OEEF) on the second step of Wittig reaction (i. e. the ring opening oxaphosphetane) in a model system for non-stabilized ylides. In particular, we have determined the optimal direction and strength of the electric field that should be applied to annihilate the reaction barrier of the ring opening through the polarizable molecular electric dipole (PMED) model that we have recently developed. We conclude that the application of the optimal external electric field for the oxaphosphetane ring opening favours a Bestmann-like mechanism.

One-pot Dess-Martin periodinane-mediated oxidative deprotection and olefination of trimethylsilyl-protected pyranosides and pyranoses

The selective functionalization of carbohydrates provides a powerful method for introducing structural complexity, allowing access to unique drug scaffolds with distinctive pharmaceutical profiles. Herein, we describe an efficient and selective carbon-carbon bond forming reaction of a variety of common trimethylsilyl-protected pyranosides and pyranoses at C-6 using a one-pot Dess-Martin periodinane-mediated oxidation deprotection. This is followed by addition of stabilized and non-stabilized ylides to generate alkenoate carbohydrates and related analogs in good to moderate yields. We also report on the rapid deprotection of the remaining trimethylsilyl ether groups in near quantitative yields using an acidic resin-mediated ethanolysis.

Ultrasound-Assisted Wittig Reaction for the Synthesis of 3-Substituted 4-Chloroquinolines and Quinolin-4(1H)-ones with Extended π-Conjugated Systems

3-(Vinyl-/buta-1,3-dien-1-yl/4-phenylbuta-1,3-dien-1-yl)-4-chloro quinolines and quinolin-4(1H)-ones were synthesized by ultrasound-assisted Wittig reaction of the corresponding 4-chloro-3-formylquinoline and 3-formylquinolin-4(1H)-ones with nonstabilized ylides. Ease execution, mild conditions, and high yields make this method exploitable for the generation of libraries of 3-substituted 4-chloroquinolines and quinolin-4(1H)-ones with extended π-conjugated systems. To demonstrate the usefulness of these compounds as precursors for the synthesis of more complex structures, 3-vinylquinolin-4(1H)-ones were used as dienes in the Diels–Alder reaction with N-methylmaleimide to produce novel acridone derivatives. The attempted Diels–Alder reaction with 3-(buta-1,3-dien-1-yl)quinolin-4(1H)-one did not afford the expected cycloadduct; instead, 2-methyl-2H-pyrano[3,2-c]quinoline was obtained. The structures and stereochemistry of the new compounds were established by NMR studies.

Observation of intermediates in Wittig reactions of non-stabilized phosphonium ylides bearing a phosphaheteratriptycene skeleton containing Group 15 elements with benzaldehyde

The heteroatom effect of Group 15 elements (P, As, Sb and Bi) has been investigated on stereochemical drift in the Wittig reactions of non-stabilized phosphonium ylides bearing a phosphaheteratriptycene skeleton with benzaldehyde. 1,2-Oxaphosphetanes were observed as intermediates and the isomerization from cis-form to trans-form, the origin of stereochemical drift, was detected between −90 °C and 25 °C by VT-31P{1H} NMR spectroscopy. The isomerization was found to start at lower temperatures as the raw number of heavier period elements. Cross experiments showed that the isomerization occurred through equilibrium between 1,2-oxaphosphetanes and phosphonium ylides-benzaldehyde.GRAPHICAL ABSTRACT

Wittig reactions of non-stabilized phosphonium ylides bearing a phosphaheteratriptycene skeleton containing group 14 and 15 elements with benzaldehyde

Wittig reactions of non-stabilized phosphonium ylides bearing a phosphaheteratriptycene skeleton containing Group 14 and 15 elements (PhSi, PhGe, PhSn, n-BuSn, P, As, Sb, and Bi) at another bridgehead position with benzaldehyde provided (Z)-olefins as a major product in the cases of period 3 elements (PhSi, P) and (E)-olefins as a major product in the cases of below period 4 elements (PhGe, PhSn, n-BuSn, As, Sb, and Bi). These results are attributed to stereochemical drift of the intermediates come from the heteroatom effect at another bridgehead position of the phosphaheteratriptycene skeleton.

Efficient synthesis of functionalized olefins by Wittig reaction using Amberlite resin as a mild base

ABSTRACTA convenient procedure for the synthesis of olefins by the reaction of stabilized, semistabilized, and nonstabilized phosphorous ylides with various aldehydes or ketone using Amberlite resin as a mild base is described. Our developed method offers facile and racemization-free synthesis of α,β-unsaturated amino esters and chiral allylic amine. The developed methodology offers mild reaction conditions, high efficiency, and facile isolation of the final products, a practical alternative to known procedures.

The E/Z selectivity in gas phase Wittig reaction of non-stabilized, semi-stabilized and stabilized Me3P and Ph3P phosphorus ylides with monocyclic ketone: A computational study

The gas phase Wittig reactions of non-stabilized (X3P=CHMe), semi-stabilized (X3P=CHPh) and stabilized (X3P=CHCO2Me) ylides (X=methyl or phenyl group) with 2,2-di-methyl cyclopentanone have been investigated at B3LYP/6-31G∗∗ level of theory to understand the E/Z selectivity. Our results strongly support the generally accepted salt free oxaphosphetane mechanism. In reactions with all ylides, a high E selectivity was observed. It is shown that the E/Z selectivity cannot be fully understood without considering the energy of the elimination TS in reactions of non- and semi-stabilized Me3P ylides. The reversibility of oxaphosphetane formation is explained by the influence of the ylide stabilization and nature of the substituents on the phosphorus of the ylide and was observed in the reactions of non- and semi-stabilized Me3P ylide reactions only. It is shown that the puckering ability of addition TS doesn’t depend on ylide stabilization but an interplay of 1,2; 1,3 and CH⋯O interactions decides the geometry of TS1s and that the selectivity is determined by the combined effect of 1,2 and 1,3 steric interactions. In all reactions, addition transition states were found to be planar in Z isomers and very slightly puckered in the E isomers. Due to the low reactivity of 2,2-dimethyl cyclopentanone, the first steps are slightly exothermic in reactions with non-stabilized ylides and endothermic in reactions involving semi-stabilized and stabilized ylides.

E-Selective Wittig reactions using a nonstabilized phosphonium ylide bearing a phosphastibatriptycene skeleton with benzaldehydes under salt-free conditions

GRAPHICAL ABSTRACT

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives.

We provide a comprehensive account of the 1,3-dipolar cycloaddition reactions of azomethine ylides with carbonyl dipolarophiles. Many different azomethine ylides have been studied, including stabilized and non-stabilized ylides. Of the carbonyl dipolarophiles, aldehydes including formaldehyde are the most studied, although there are now examples of cycloadditions with ketones, ketenes and carboxyl systems, in particular isatoic anhydrides and phthalic anhydrides. Intramolecular cycloadditions with esters can also occur under certain circumstances. The oxazolidine cycloadducts undergo a range of reactions triggered by the ring-opening of the oxazolidine ring system.

Experimental and Theoretical Study of the Effectiveness and Stability of Gold(I) Catalysts Used in the Synthesis of Cyclic Acetals

Different [AuL]+ fragments (L = tertiary phosphines, ylides, or NHC carbene) have been tested under mild conditions as suitable catalysts for the transformation of terminal or internal alkynes into the corresponding cyclic acetals upon reaction with ethylene glycol. We have obtained a moderate to negligible activity when using tertiary phosphines or nonstabilized ylides as ligands. However, a very high catalytic activity is reached when the IPr N-heterocyclic carbene ligand is used. We have analyzed the key stages in this type of gold-catalyzed reaction, namely, (i) electronic activation (alkynophilicity); (ii) protodeauration; and (iii) decomposition of the gold catalyst. The first two stages have been analyzed through DFT computation of the minimum-energy reaction pathways employing different catalysts. An explanation of the catalysts’ stability has been proposed through the analysis of in situ time-resolved nuclear magnetic resonance spectra of the catalysts.

ChemInform Abstract: Catalytic Wittig Reactions of Semi‐ and Nonstabilized Ylides Enabled by Ylide Tuning.

AbstractDifferent phosphinoxide catalysts are employed in the Wittig reaction between aromatic aldehydes, benzyl halogenides, and alkyl halogenides.

Aryltriolborates as Air- and Water-Stable Bases for Wittig Olefination

Tetrabutylammonium aryltriolborates have been synthesized in 37–66% yield by a one-pot procedure from arylboronic acids, 1,1,1-tris(hydroxymethyl)ethane, and aqueous tetrabutylammonium hydroxide. The aryltriolborates can be used as bases in Wittig reactions of aromatic aldehydes with all three types of phosphorus ylides: stabilized and semistabilized ylides can be generated at room temperature, and nonstabilized ylides at 120 °C (bath temperature).

Catalytic wittig reactions of semi- and nonstabilized ylides enabled by ylide tuning.

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

ChemInform Abstract: Use of Silver Carbonate in the Wittig Reaction.

An efficient synthesis of olefins by the coupling of stabilized, semistabilized, and nonstabilized phosphorus ylides with various carbonyl compounds in the presence of silver carbonate is reported. Wittig olefination of aromatic, heteroaromatic, and aliphatic aldehydes (yields >63%) and a ketone (yield 42%) are demonstrated. These reactions proceed overnight at room temperature, under weakly basic conditions, and as such extend the applicability of the Wittig reaction to base-sensitive reactants.

Wittig Reaction: Role of Steric Effects in Explaining the Prevalent Formation of Z Olefin from Nonstabilized Ylides

For understanding the mechanism involved in the Wittig reaction, it is important to know the factors which influence the stability of 1,2-oxaphosphetane intermediates with pentacoordinate phosphorus; in these intermediates, the steric factor plays a predominant role. Studying the Wittig reaction between nonstabilized ylides and different aldehydes, we noted that the stereochemical outcome driving toward Z-olefin formation was influenced only by different steric factors. The proposed mechanism differs from those previously reported because it underlines the fundamental role of the two cis/trans oxaphosphetane intermediates with the oxygen atom in equatorial position.

ChemInform Abstract: Distinction Between Polar and Electron-Transfer Routes. A Mechanistic Study on the Wittig Reactions of Nonstabilized Ylides.

The Wittig reaction of nonstabilized ylides with benzaldehyde and benzophenone was investigated in detail by means of carbonyl- 14 C kinetic isotope effects, substituent effects, and isotope-scrambling and probe experiments. The reaction with benzophenone gave the carbon isotope effects and the Hammett p values of considerable magnitude both in Li salt-free and salt-present conditions. In contrast, they are quite small for the reaction with benzaldehyde. Enone-isomerization and dehalogenation probe experiments indicated that the nonstabilized ylide has enough ability to transfer an electron to benzaldehyde and benzophenone

Convenient Route to Primary (Z)-Allyl Amines and Homologs

A convenient two-step procedure for the synthesis of primary (Z)-allyl amines, (Z)-homoallyl amines [(Z)-but-3-enylamines], and (Z)-pent-4-enylamines using the Wittig reaction was achieved. The use of nonstabilized ylides from triphenylphosphonium salt, potassium salt, and apolar solvent produced (Z/E)-geometric isomer ratios generally greater than 1.6. The amine moiety was masked using a phtalimide group that was removed successfully in the last step of the process in two different conditions, NH2NH2/EtOH/rt or CH3NH2/EtOH/rt. However, in some cases, reduction of the C = C double bond in the deprotection with hydrazine was concomitantly observed.

Synthesis of Unsaturated Organotrifluoroborates via Wittig and Horner−Wadsworth−Emmons Olefination

The stereoselective synthesis of unsaturated organotrifluoroborates by using the Wittig and Horner-Wadsworth-Emmons olefination is described. These reactions were general for both alkyl- and aryltrifluoroborates. The synthesis of di- and trisubstituted olefins was achieved by using formyl- and acetyl-substituted organotrifluoroborates. The products were isolated in moderate to excellent yield. The Wittig reaction with nonstabilized ylides was performed under salt free conditions in most cases to obtain the Z-isomer. The E-isomer was accessed by using preformed stabilized ylides. The Horner-Wadsworth-Emmons reaction also gave the E-isomer as expected.

(E)‐Selective Wittig Reactions of Garner′s Aldehyde with Nonstabilized Ylides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

( E)-Selective Wittig reactions of Garner's aldehyde with nonstabilized ylides

In the Wittig olefination reactions of Garner's aldehyde with certain nonstabilized ylides, the ( E)-alkenes could be produced as a major product by simply quenching the reactions with a large excess of MeOH at −78 °C. Even under the salt-free conditions, more than a 10:1 ratio of the ( E)- to ( Z)-alkene was resulted consistently from the ylides of a linear alkyl chain. Without addition of MeOH, usual selectivity for the ( Z)-alkene was obtained in a ratio of 94:6.