Trimethylsilyldiazomethane

Form Supplied in commercially available as 2 M and 10 w/w% solutions in hexane, and 10 w/w% solution in CH2CI2 also available as 2 M solutions in diethyl ether or hexanes. 

Analysis of Reagent Purity concentration in hexane is determined by H NMR.  

Preparative Methods prepared by the diazo-transfer reaction of Trimethylsilylmethylmagnesium Chloride with Diphenyl Phosphorazidate (DPPA) (eq 1).  

Handling, Storage, and Precautions should be protected from light. 

Takayuki Shioiri Toyohiko Aoyama Nagoya City University, Nagoya, Japan 

Related Reagents. Lithium Cyano(dimethylphenylsilyl)-cuprate Trimethylsilyllithium. 

(a) Sarkar, T. K., Synthesis 1990,969. (b) Colvin, E. W. Silicon Reagents in Organic Synthesis, Academic New York, 1988 pp 27,51. (c) Colvin, E. W. Silicon in Organic Synthesis, Butterworths Boston, 1981 p 134. 

Various ketones react with TMSCHN2 in the presence of Boron Trifluoride Etherate to give the chain or ring homologated ketones (eqs 4-6). The bulky trimethylsilyl group of TMSCHN2 allows 

Alkylation of the lithium salt of TMSCHN2 (TMSC(Li)N2) gives a-trimethylsilyl diazoalkanes which are useful for the preparation of vinylsilanes and acylsilanes. Decomposition of a-trimethylsilyl diazoalkanes in the presence of a catalytic amount of Copper(I) Chloride gives mainly ( )-vinylsilanes (eq 12),  

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Accordingly, we examined the cycloaddition reactions using trimethylsilyldiazomethane and 3-crotonoyl-2-oxazolidinone in the presence of a wide variety of Lewis... 

Unfortunately the reaction of trimethylsilyldiazomethane with 2-acryloyl-2-oxa-zolidinone led to a racemic result. Since 2-acryloyl-2-oxazolidinone has a terminal-... 

The desilylacetylated qrcloadducts, produced from the reactions of trimethylsilyl-diazomethane with 3-crotonoyl-2-oxazolidinone or 3-crotonoyl-4,4-dimethyl-2-oxa-zolidinone, were transformed to methyl traws-l-acetyl-4-methyl-l-pyrazoline-5-car-boxylate through the reactions with dimethoxymagnesium at -20 °C. When the optical rotations and chiral HPLC data were compared between these two esters, it was found that these two products had opposite absolute stereochemistry (Scheme 7.39). The absolute configuration was identified on the basis of the X-ray-determined structure of the major diastereomer of cycloadduct derived from the reaction of trimethylsilyldiazomethane to (S)-3-crotonoyl-4-methyl-2-oxazolidi-none. 

Jorgensen has recently reported similar enantioselective reactions between N-tosylimines 107 and trimethylsilyldiazomethane (TMSD) catalyzed by chiral Lewis acid complexes (Scheme 1.32) [57, 53]. The cis-aziridine could be obtained in 72% ee with use of a BINAP-copper(i) catalyst, but when a bisoxazoline-copper(i) complex was used the corresponding trans isomer was fonned in 69% ee but with very poor diastereoselectivity. 

Trimethylsilyldiazomethane reacts under similar conditions with N-tosylimines in the presence of (ft)-Tol-BINAP, with better enantiocontrol, but the process does not live up to the standards expected of modern asymmetric transformations (Scheme 4.28) [34],... 

For a method of conducting the reaction with trimethylsilyldiazomethane instead of CH2N2, see Aoyama, T Shioiri, T. Tetrahedron Lett., 1980, 21, 4461. 

UV photolysis (Chapman et al., 1976 Chedekel et al., 1976) and vacuum pyrolysis (Mal tsev et al., 1980) of trimethylsilyldiazomethane [122]. The silene formation occurred as a result of fast isomerization of the primary reaction product, excited singlet trimethylsilylcarbene [123] (the ground state of this carbene is triplet). When the gas-phase reaction mixture was diluted with inert gas (helium) singlet-triplet conversion took place due to intermolecular collisions and loss of excitation. As a result the final products [124] of formal dimerization of the triplet carbene [123] were obtained. 

Aryldiazomethane can also be used for iron porphyrin-catalyzed alkene cyclopropanation [55]. For example, the treatment of p-tolyldiazomethane with styrene in the presence of [Fe(TTP)] afforded the corresponding arylcyclopropapane in 79% yield with a high transicis ratio of 14 1 (eq. 1 in Scheme 11). Interestingly, when bulkier mesityldiazomethane was used as carbene source, ds-selectivity was observed (cisitrans = 2.0 1). Additionally, mesityldiazomethane was found to react with frans-p-styrene, the latter was found not to react with EDA or trimethyl-silyldiazomethane under the similar reaction conditions, to give l-mesityl-2-methyl-3-phenylcyclopropane in 35% yield. Trimethylsilyldiazomethane is also an active carbene source for [Fe(TTP)]-catalyzed cyclopropanation of styrene, affording l-phenyl-2-trimethylsilylcyclopropane in 89% yield with transicis ratio of 10 1 (eq. 2 in Scheme 11). 

The scope of the multi-residue method is extended permanently by testing and then including further active substances that can be determined by GC. Acidic analytes (such as phenoxyacetic acids or RCOOH metabolites) are included into the homogeneous partitioning by acidifying the raw extracts to a pH below the pKs value of the carboxylic acids. To include these analytes in the GC determination scheme they have to be derivatized with diazomethane, diazoethane, trimethylsilyldiazomethane, acidic esterification or benzylation, or by silanizing the COOH moiety. 

Bispyribac-sodium is recovered as the free acid, bispyribac, from plant material and soil by acetonitrile-water (4 1, v/v) solvent extraction. After filtration, the acetoni-tirile is evaporated under reduced pressure. The aqueous residue is dissolved in buffer solution (pH 7.4) and washed with ethyl acetate to separate the impurities from the extract. Then the solution is acidified and extracted with ethyl acetate. The ethyl acetate is evaporated. The residue is methylated with trimethylsilyldiazomethane. 

Dissolve the residue prepared as in Section 6.1.2 or 6.2.1 in 1 mL of diethyl ether-methanol (4 1, v/v). Add 0.8 mL of 10% trimethylsilyldiazomethane in n-hexane to the mixture and allow the reaction mixture to stand at room temperature for 1 h. Concentrate the mixture to dryness under reduced pressure. 

Methylation of the residues of the ethyl acetate extract prepared in Section 6.2.1 should immediately be performed with trimethylsilyldiazomethane, because bispyribac is unstable under acidic conditions. 

Suspend the residue with 1 mL of acetone. Add 50 pL of methanol and 100 pL of 10% trimethylsilyldiazomethane-hexane solution and allow to stand for about 30 min at room temperature. Concentrate the reaction mixture under an N2 gas flow at about 40 °C. 

Alkylating reagents such as boron trifluoride-methanol, sulfuric acid-methanol, methanol-hydrochloric acid and methyl iodine-sodium hydride do not react efficiently with pyrithiobac. Trimethylsilyldiazomethane may be used for the methyl-ation of pyrithiobac. 

The main drawback to this reaction is the toxicity of diazomethane and some of its precursors. Diazomethane is also potentially explosive. Trimethylsilyldia-zomethane is an alternative reagent,42 which is safer and frequently used in preparation of methyl esters from carboxylic acids.43 Trimethylsilyldiazomethane also O-methylates alcohols.44 The latter reactions occur in the presence of fluoroboric acid in dichloromethane. 

On the other hand, 3,5-disubstituted [l,2,4]diazaphosphole 29 could be obtained from the reaction of tri-ferf-butylphenylphosphaethyne (25) with freshly prepared lithiated trimethylsilyldiazomethane (30) and subsequent treatment of the initially formed diazaphospholide ion (31) with trifluoroacetic acid (Scheme 9) [33],... 

In a quite different approach, shown in Scheme 204, cycloaddition of nitrile 1232 to trimethylsilyldiazomethane provides silylated triazole 1233, isolated in 75% yield. Treatment with tetrabutylammonium fluoride removes the trimethylsilyl group and simultaneously the silyl protection of the carboxylic group to afford 4-substituted triazole derivative 1234 in 81% yield <2003PEN699>. 

Reaction of lithium trimethylsilyldiazomethane (TMSC(Li)N2) with thiocarbonyl compounds has proved to be a convenient method for the preparation of 5-substituted 1,2,3-thiadiazoles. This reaction is very similar to the Pechmann-Nold reaction but probably does not proceed through a dipolar cycloaddition pathway. A number of examples of this type of reaction were described in CHEC-II(1996). More recently, it was reported that TMSCN2Li also reacts with diethylaminothiocarbonyl chloride to afford a mixture of 1,2,3-thiadiazoles 66 and 67 (Equation 19) <1997BSB533>. 

The use of thiocarbonyl compounds and also trimethylsilyldiazomethane in the Pechmann-Nold synthesis has greatly increased the scope of this reaction in recent years. Wolff s synthesis has also benefited from advances in the synthesis of both diazoketones and thionating reagents. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

The use of a carbene as the one-carbon component provides an alternative and efficient entry into the [4 + 2+1]-reaction manifold. Montgomery and Ni have developed a nickel-catalyzed process where the carbene is generated from trimethylsilyldiazomethane (Scheme 45).135 It is not known, however, if the seven-membered ring forms via a Cope rearrangement of a divinylcylopropane or if the metal is intimately involved in the step that leads directly to... 

Reaction of the digermene 57 with diazomethane or trimethylsilyldiazomethane yields the azadigermiranes 58 via a [2+l]-cycloaddition (Equation (119)).158 Coupling of a cyclic carbene and a cyclic germylene furnishes the zwitter-ionic species 59 (Equation (120)).159... 

An example of an iron-catalyzed C-C bond formation reaction was reported in 2001 [89]. Treatment of propargyl sulfides 87 with trimethylsilyldiazomethane in the presence of 5 mol% FeCl2(dppb) gave substituted homoallenylsilanes 88 in good to moderate yields (Scheme 3.43). The silanes 88d and 88e, which bear two centers of chirality, were obtained as 1 1 mixtures of diastereomers. Slight diastereoselectivity (2 1) was seen for the formation 88f, which is an axially chiral allene with a sterogenic center. 

In contrast to A5-phosphorus-substituted diazo derivatives, which have been known for a long time,22 the synthesis of the first o -diazophosphine was reported as recently as 1985.23 This compound, namely the [bis(diiso-propylamino)phosphino](trimethylsilyl)diazomethane la, was obtained by treatment of the lithium salt of trimethylsilyldiazomethane with 1 equiv of bis(diisopropylamino)chlorophosphine. 

Diphenyl phosphorszldate can be replaced with diethyl phosphorazidate in the above procedure. Use of other azides such as p-toluenesulfonyl azide, p-methoxybenzyloxycarbonyl azide, diphenylphosphinic azide, or diphenylthio-phosphinic azide is less satisfactory. No reaction occurs when trimethylsilyl azide, dimethylthiophosphinic azide, or alkaline azides are used, while decomposition of formed trimethylsilyldiazomethane seems to occur when... 

The NMR of the hexane solution showed the presence of a trace of diethyl ether. The concentration of trimethylsilyldiazomethane was determined by the NMR analysis as follows Ninety-one milligrams of dibenzyl was... 

Trimethylsilyldiazomethane, as a stable and safe substitute for hazardous diazomethane, is useful both as a reagent for introducing a Cj-unit and as a C-N-N synthon for the preparation of azoles. Many methods are described in the literature for the preparation of trimethylsilyldiazomethane, including the trimethylsilylation of diazomethane (7-74S), the alkaline decomposition of N-nitroso-N-(trimethylsilylmethyl)amides (25-61%) and the diazo group transfer reaction of trimethylsilylmethyllithium with p-toluenesulfonyl azide (38%). The present modified diazo group transfer method appears to be the most practical, high-yield, and large scale procedure for the preparation of... 

A very similar reaction to that of Pechmann and Nold but which probably does not proceed through a dipolar cycloaddition manifold is the formation of 1,2,3-thiadiazole (6) via a thionoester and lithium trimethylsilyldiazomethane (Equation (17)) <86H(24)589>. Lithium trimethylsilyl-diazomethane also reacts with thioketones to produce 1,2,3-thiadiazoles <87H(26)1467>. 

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