Use Of Silylation Research Articles

ChemInform Abstract: Recent Advances in Silyl Protection of Alcohols

AbstractReview: 82 refs.

Pd(0)-Catalyzed Alkene Oxy- and Aminoalkynylation with Aliphatic Bromoacetylenes

Tetrahydrofurans and pyrrolidines are among the most important heterocycles found in bioactive compounds. Cyclization-functionalization domino reactions of alcohols or amines onto olefins constitute one of the most efficient methods to access them. In this context, oxy- and aminoalkynylation are especially important reactions, because of the numerous transformations possible with the triple bond of acetylenes, yet these methods have been limited to the use of silyl protected acetylenes. Herein, we report the first palladium-catalyzed oxy- and aminoalkynylation using aliphatic bromoalkynes, which proceeded with high diastereoselectivity and functional group tolerance. A one-pot hydrogenation of the triple bond gave then access to alkyl-substituted tetrahydrofurans and pyrroldines. Finally, a detailed study of the side products formed during the reaction gave a first insight into the reaction mechanism.

Simple and efficient preparation of 3-substituted 6-(4-chlorophenyl)-9-methyl-12H-[1]benzofuro[3,2-e][1,2,4]triazolo[4,3-b][1,2]diazepines via a silylation–amination reaction

A series of new 3-substituted 6-(4-chlorophenyl)-9-methyl-12H-[1]benzofuro[3,2-e][1,2,4]triazolo[4,3-b][1,2]diazepines was synthesized from the corresponding bicyclic 1-(4-chlorophenyl)-3,5-dihydro-8-methyl-4H-[1]benzofuro[2,3-d][1,2]diazepin-4-one. The synthesis strategy makes use of silylation–amination as the key step, allowing a wide range of derivatives to be prepared. .

Silyl Nitronate 1,3-Dipolar Cycloaddition Reactions with meso-Tetraarylporphyrins

Isoxazoline-fused chlorins were obtained in moderate yields from the reaction of silyl nitronates and 5,10,15,20-tetra(pentafluorophenyl)porphyrin in toluene at 85 °C. Chlorins are a class of reduced porphyrins characterized by one saturated pyrrolic Cβ–Cβ bond. Besides being at the core of natural photosynthetic system such as chlorophylls, chlorins have attracted a great deal of attention due to their distinctive optical and photochemical properties. Most notably, their strong absorption near the red end of the visible spectrum has made them one of the highly desired tetrapyrrolic macrocycles for their potential utility as second generation photosensitizers in photodynamic therapy of cancer. Such and other newly emerging applications have made these molecules attractive targets for chemical synthesis. Apart from total synthesis and modification of naturally occurring chlorins, a highly practical strategy has been the derivatization of simple and easily available porphyrins. In this context, amongst β-β addition reactions, 1,3-dipolar cycloaddition reactions feature prominently as an one step strategy to obtain five-membered heterocycle-fused chlorins. Not surprisingly, a host of dipolar molecules including azomethine ylides, diazoalkanes, nitrones, carbonyl ylides, nitrile oxides and nitrile imines have been examined for their 1,3-dipolar cycloaddition reaction with porphyrins. Isoxazolines are noteworthy for their biological applications and have proven particularly useful as precursors for several multi-functional intermediates such as β-hydroxyketones, α,β-unsaturated ketones, γ -amino alcohols, etc., to name a few. Although nitrile oxide 1,3-dipolar cycloaddition provides access to isoxazoline-fused chlorins, the method suffers from poor selectivity (both chlorins and bacteriochlorins are formed) and instability of the reagent. Noting the difference in reactivity we envisaged that an alternate strategy could be the use of silyl nitronates as 1,3-dipoles to make isoxazoline-fused chlorins. Here, we report the results of our initial investigation of the reactivity of silyl nitronates towards meso-tetraarylporphyrins. Published as: Ebrahim, M. M.; Moreau, M.; Senge, M. O. (2011): Silyl Nitronate 1,3-Dipolar Cycloaddition Reactions with meso-Tetraarylporphyrins. Heterocycles 83, 627–630.

Self-Consistent Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C via Controlled Oligomerization

Despite the prevalence of repeating subunits in chiral natural products, stereocontrolled oligomerization is a largely unexplored strategy for construction of carbon skeletal frameworks. This report describes the use of silyl glyoxylates as dipolar glycolic acid synthons in a controlled oligomerization reaction for the efficient construction of the squalene synthase inhibitor zaragozic acid C. This new methodology allows rapid, stereocontrolled formation of the carbon skeleton with a desirable protecting group scheme while minimizing functional group repair and oxidation state manipulations.

GC–MS Analysis of gamma-Hydroxybutyric Acid Analogs

An upper-division forensic chemistry experiment is described. It involves using glycolic acid and sodium glycolate as analogs of γ-hydroxybutyric acid and its sodium salt. The experiment shows the use of silylation in GC–MS analysis and gives students the opportunity to work with a commonly used silylating reagent, N,O-bis[trimethylsilyl]trifluoroacetamide (BSTFA). GC–MS is used to show the problem with analyzing an organic acid without derivatization and to analyze the products of silylation.

The use of silylation for minimizing the interference effects caused by contamination in ultra-low level mercury analytics.

The use of silylation of glassware in mercury analytics was investigated. By treating the glassware with 5% (v/v) dichlorodimethylsilane in toluene, the surfaces of the vessels were inactivated. Method development proved that silylation can extend the range of stabile, contamination-free area as low as 1 ng/L mercury without any significant investments in laboratory clean-room facilities. The resilylation had to be done once a month.

Use of silyl ethers as fluoride scavengers in RNA synthesis

Use of a fluoride ion scavenger significantly simplifies isolation of synthetic RNA.

Pore size and surface texture modification of silica via trialkylsilylation

Although surface modification of silica via silylation is often undertaken to change surface chemistry and, hence, adsorption characteristics, the use of silylation for modifying pore size, size distribution, and surface texture is rarely considered. In principle, by use of silylating agents of the form R{sub n}SiCl{sub 4-n} where n is typically 3, pore size and texture may be varied by changing the R group, n, and/or surface coverage. When the silica is microporous, this approach should be particularly effective for changing the pore size. However, many questions exist concerning the effect of small-scale surface roughness, the fractional surface coverage, and R group size on the effective pore size. Modification of various silicas (Vycor, CPG-75, two-step acid/base catalyzed silica gel) was conducted by trialkylsilylation. The degree of silylation/surface coverage was monitored by thermogravimetric analysis and elemental analysis. Pore structure was studied by nitrogen adsorption and condensation and small angle X-ray scattering. The results show that surface area, surface texture, pore size distribution, and total pore volume are indeed changed in a controlled fashion due to silylation. Generally, the mean pore size is smaller, the pore size distribution is significantly narrower, and the pore surface is smoother after silylation. The magnitudes of more » those changes are shown as a function of R, coverage, and surface roughness. 17 refs., 8 figs., 4 tabs. « less

The synthesis of oligoribonucleotides. III. The use of silyl protecting groups in nucleoside and nucleotide chemistry. VIII

The synthesis of all isomeric mono- and disilyl derivatives of cytidine, guanosine, and their N-benzoyl analogues using the tert-butyldimethylsilyl protecting group is described. These compounds and those containing a 5′-monomethoxytrityl group have been condensed via the phosphodichloridite procedure to produce nucleotides rapidly and in good yields. The synthesis of 2′–5′-linked nucleotides is described. A cautionary note is introduced in regard to the preparation of 5′-monomethoxytritylguanosine and a novel methanolysis of certain N-benzoylcytidines is mentioned.

The synthesis of oligoribonucleotides. II. The use of silyl protecting groups in nucleoside and nucleotide chemistry. VII

The synthesis of oligonucleotides derived from uridine and adenosine using the tert-butyldimethylsilyl protecting group and the trichloroethylphosphorodichloridite condensation procedure is described. These procedures involve rapid preparation of protected starting materials and equally rapid condensation of units to form nucleotides. Optimum yields using collidine as base in tetrahydrofuran as solvent are between 65 and 80%. The utility of the procedure is rendered complete by the capability to remove both the phosphate protecting groups and the alkylsilyl groups in a single 30 min step using tetrabutylammonium fluoride in tetrahydrofuran.

The Use of Silylation in Organic Syntheses

AbstractThe term silylation is used to denote the introduction of a triorganosilyl moiety, especially the trimethylsilyl species, into organic compounds. ‐ Silylated amino acids and sugars are particularly suitable for the syntheses of peptides and saccharides, respectively, since the silyl group can be cleaved off readily under mild conditions. Many diamines undergo ring closure, e.g. with phosgene, only after silylation. ‐ O‐silylated lactim ethers (i.e. cyclic imino ethers) are converted into N‐alkyl derivatives by alkyl halides. Compounds with a strongly polarized SiC bond may be used for chain extension. Silyl esters of halogeno fatty acids yield lactones with silver cyanate. ‐ Trimethylsilyl azide is thermally very stable and behaves like organic azides. It reacts with acetylenic compounds, trialkylphosphines, and triarylphosphines to yield silylated triazole derivatives, trialkylphosphines N‐silylimines, and triarylphosphines to yield silylated triazole dervatives, trialkylphosphine N‐silylimines, and triarylphosphine N‐silylimines, respectively, from which the silyl groups can be removed under mild conditions.