Acetylenic Grignard Reagents Research Articles

Palladium-Free, Highly Efficient Mesoporous Tin Silicates Catalytic Acyl Sonogashira Coupling Reaction

Three-dimensional mesoporous tin silicates (PS-2) with different Si/Sn mole ratios are synthesized by direct hydrothermal treatment via a soft-templating technique under acidic conditions. The first example of PS-2 catalysts composed of tunable textural properties and designed to overcome the problems associated with stoichiometric acetylenic Grignard reagents and large amounts of uneconomical Pd catalysts indeed shows that a new synthetic approach toward direct acyl Sonogashira coupling reaction through C–C coupling has been developed under palladium metal- and ligand-free conditions. Both aromatic and aliphatic alkynes could react with acid halides to produce ynones and its derivatives under solvent-free conditions.

Nickel-catalyzed cross-coupling reaction of acetylenic sulfones with alkynyl Grignard reagents: a facile method for the preparation of unsymmetrical 1,3-diynes

Abstract The cross-coupling reaction of acetylenic sulfones with acetylenic Grignard reagents was realized by using Ni(acac) 2 as catalyst to afford unsymmetrical 1,3-diynes under mild conditions without homocoupling byproducts. By using this method, 1,4-diaryl-1,3-diynes could be obtained in moderate to good yields (59–83%), whereas, the yields for alkyl substituted 1,3-diynes are lower (30–54%).

A convergent approach toward phoslactomycins and leustroducsins

Synthetic studies devoted to the development of a convergent approach toward phoslactomycins and leustroducsins, a family of natural products inhibitors of serine/threonine phosphatase 2A, are reported. A formal synthesis of phoslactomycin B was achieved in which the key steps are a [2,3]-Wittig rearrangement to control the C4 and C5 stereocenters, a diastereoselective addition of an acetylenic Grignard reagent to an α-alkoxy ketone to create the C8 tertiary alcohol, and a relay ring-closing metathesis to construct the α,β-unsaturated δ-lactone. In this approach, all the stereocenters originate, either directly or indirectly, from catalytic enantioselective reductions of acetylenic ketones.

Synthesis of Quinolines by Catalyzed Cyclodehydration of Aminoaryl-2-yn-1-ols

A general synthesis of substituted quinolines through a copper- or palladium-catalyzed 6-endo-dig annulation-dehydration of amino­aryl-2-yn-1-ols, easily prepared using readily available acetylenic Grignard reagents, is reported. The reaction may be carried out in one pot, which is of significance since the aminoaryl-2-yn-1-ols are unstable towards purification. Unfortunately, the reaction of TMS alkynes (R4 = TMS) led to a loss of the TMS group. Otherwise, the availability of TMS-substituted quinoline products may open new routes for further desilylative substitution chemistry. The scope of the reaction with respect to substitution on both reaction partners was inadequately tested.

Acetylene‐Substituted Phosphane Oxides: Building Blocks for Macrocycles

AbstractPhosphorus‐based macrocycles with acetylenic scaffolds have been built from acetylene‐substituted phosphane oxides that were formed from diisopropylphosphoramidic dibromide (3) and an acetylenic Grignard reagent. The four‐ and six‐edged macrocycles 15 and 16, in which the iPr2NP(O) units are connected through 1,3‐butadiyne rods, were obtained from the monosilylated derivative of iPr2NP(O)(C2H)2 (7) by multiple acetylene coupling reactions under oxidative Hay conditions. Reaction of iPr2NP(O)(Br)2 (3) with lithiated 1,2‐diethynylbenzene gave a mixture of cis and trans monocyclic bis(phosphane oxide) 18. An X‐ray crystal structure determination of the trans isomer shows the ring structure to adopt a puckered form.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Building blocks for phospha[ n]pericyclynes

Reaction of i-Pr 2NPCl 2 with acetylenic Grignard reagents resulted in the formation of new acetylenic substituted phosphorus building blocks. These building blocks can be protected by forming the corresponding W(CO) 5 complex and the O and S derivatives for added stability as was demonstrated for aminophosphine ( 11a). From this building block, very sensitive product mixtures containing tetraphospha[4]pericyclynes ( 16) were obtained. In addition, the amino-substituent of phosphines ( 11) could be removed upon treatment with HCl to give chlorophosphine ( 18) from which novel trisethynylphosphines ( 19) bearing different substituted alkynes were obtained that may serve as building blocks for novel three-dimensional phospha-acetylenic scaffolds such as the (di)ethynyl-expanded phosphacubanes 8 and 25 that, according to DFT calculations, have a higher degree of cyclic electron delocalization and reduced HOMO–LUMO gaps compared to their carbon-analogues.

Computational study of the Grignard reaction with alkynes

The complexation of MgX 2, MeMgX, and Me 2Mg (X=Cl, Br) with propyne have been studied both in the gas phase and in the presence of dimethyl ether (Me 2O) by means of the density functional theory B3LYP/6-31+G* method. Solvation was modeled using the supermolecule approach. The complex formation between disolvated magnesium compound and alkyne is connected with replacement of a coordinated solvent molecule by the alkyne, being necessary for the reaction to proceed to the end. The reaction towards end products, an acetylenic Grignard reagent and an alkane, is exothermic. The transition state has a cyclic structure, which is almost triangular with practically linear proton transfer. The transition state resembles more the reagents than the products.

Stereocontrolled synthesis of trifluoromethylated (E)- or (Z)-ynenyl sulfones via sequential transformations

Diethyl 1-(phenylsulfonyl)ethylphosphonate 1 was treated with n-butyllithium in tetrahydrofuran (THF) at −78 °C and the resulting carbanion 2 reacted with trifluoroacetic anhydride to give the trifluoroacylated phosphonate 3. Without isolation, 3 was attacked by lithium acetylides and elimination of phosphate anion afforded trifluoromethylated (Z)-ynenyl sulfones (Z-4) in 57–76% yields, while treatment of 3 with acetylenic Grignard reagents gave trifluoromethylated (E)-ynenyl sulfones (E-4) in 45–54% yields. The configuration of the products could be ascertained on the basis of the crystal structure. A possible mechanism for the explanation of stereochemical results is proposed.

ChemInform Abstract: Studies in the Synthesis and Biosynthesis of C‐Nucleosides

Abstract The naturally occurring C-nucleosides show marked antiturnour and antiviral properties. We have developed, over a period of years, a general synthetic route to C-nucleosides by way of acetylenic intermediates. Tri-O-benzyl-D-ribofuranose (1) reacts with acetylenic Grignard reagents to give mixtures of D-allo and D-altro diols. The latter, on ring closure by means of toluene-p-sulphonyl chloride in pyridine, gives derivatives, (2) or (3), of β-D-ribofuranosylethyne in ∼50% yield from (1).

Studies in the Synthesis and Biosynthesis of C-Nucleosides

Abstract The naturally occurring C-nucleosides show marked antiturnour and antiviral properties. We have developed, over a period of years, a general synthetic route to C-nucleosides by way of acetylenic intermediates. Tri-O-benzyl-D-ribofuranose (1) reacts with acetylenic Grignard reagents to give mixtures of D-allo and D-altro diols. The latter, on ring closure by means of toluene-p-sulphonyl chloride in pyridine, gives derivatives, (2) or (3), of β-D-ribofuranosylethyne in ∼50% yield from (1).

Dérivés diglycosyliques. Communication préliminaire

Diglycosyl Derivatives. Preliminary communicationNovel types of diglycosyl compounds, some of them bearing a resemblance to natural di‐ or tri‐saccharides are described: a diglycosyldiyne (1), a diglycosylthiophene (2), a diglycosylaziridine (3), a diglycosyldioxolane (4), as well as six C,N‐diglycosylnitrones, 9b–9f and 14. These C,N‐diglycosylnitrones, on treatment with an acetylenic Grignard reagent, led to the expected acetylenic diglycosyl‐hydroxylamine 11, whereas diglycosylisoxazolines (f. ex. 10) were obtained when these nitrones underwent 1,3‐dipolar cycloaddition to acetylenic compounds.

C-Glycosyl Nucleosides. II. Reaction of Sugar Aldehyde with Acetylenic Grignard Reagents

Reaction of acetylenic Grignard reagents with 2, 3 : 4, 5-di-o-isopropylidene-aldehydo-D-ribose (I) or 2, 4 : 3, 5-di-o-benzylidene-aldehydo-D-ribose (VII) afforded 3-epimeric heptyne derivatives (II, III and VIII, IX). The configuration of these compounds was determined from nuclear magnetic resonance and mass spectra.

Stéréochimie de réactions d'organomagnésiens sur des organosilanes optiquement actifs. Influence du solvant sur la stéréochimie des réactions

The stereochemistry of the reactions of Grignard reagents and of dialkylmagnesium with methylphenyl-α-naphthylsilane, ethylphenyl-α-naphthylsilane, vinylphenyl-α-naphthylsilane and their derivatives has been determined. The observed stereochemistry depends on the leaving group, the Grignard reagent and the reaction medium (solvent and dissolved salts). With chlorosilanes, inversion of configuration, and with methoxysilanes, retention, are always observed. In the case of fluorosilanes the stereochemistry depends on the Grignard reagent and the solvent used. α,β-Unsaturated Grignard reagents and dialkylmagnesiums react with fluorosilanes with inversion of configuration irrespective of the solvent. Saturated or acetylenic Grignard reagents and dialkylmagnesiums react with inversion of configuration in diethyl ether. The stereochemistry is generally retention of configuration with THF or DMF as solvent. The results obtained imply that electrophilic assistance by the metal is not the essential factor orientating the stereochemistry towards retention of configuration. An S N1S i mechanism does not explain all the experimental results. It seems that the observed stereocheistry is connected with the polarity and polarisability of the leaving group as well as with the relative electron donating ability of the entering nucleophile.

Poly- isooxazoles

The reaction of hydroximic chlorides on acetylenic Grignard reagents has been applied to the synthesis of unknown poly-iso oxazoles. Some linear poly- isooxazoles of unequivocal structure, viz. 3:3′:5′:3″-tri- isooxazole (IX), 3:3′:5′:5″-tri- isooxazole (XIV), 3:3′:5′:5″:3″:3‴-tetra- isooxazole (XV) and 3:3′:5′:5″:3″:3‴:5‴:5 IV:3 IV3 V-hexa- isooxazole (XVII) have been prepared.

Additions and Corrections - The Reactions of Metal Halides with Acetylenic Grignard Reagents

Additions and Corrections - The Reactions of Metal Halides with Acetylenic Grignard Reagents

The Reaction of Metal Halides with Acetylenic Grignard Reagents

The Reaction of Metal Halides with Acetylenic Grignard Reagents

The Preparation of Dialkylacetylenes from Acetylenic Grignard Reagents and Alkyl Sulfates1

The Preparation of Dialkylacetylenes from Acetylenic Grignard Reagents and Alkyl Sulfates¹

The Reaction of Ethylene Oxide with Acetylenic Grignard Reagents

The Reaction of Ethylene Oxide with Acetylenic Grignard Reagents