Lithium trimethylsilyldiazomethane

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>. 

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. 

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>. 

The addition of organometaiiics to unactivated pyrimidines normally produces unstable dihydro derivatives which readily oxidize back to the pyrimidine oxidation level, although successful conjugate addition to pyrimidinone derivatives can occur. Thus, the addition of lithium trimethylsilyldiazomethane [TMSC(Li)N2] to 1,3-dimethyluracil 418 occurred at the 6-position to produce a mixture of the two pyrazolo[4,3-rf]pyrimidine-5,7-diones 419 and 420, where the initial addition had been accompanied by cyclization <1997T7045>. 

E)-l-Trimethylsilyl-l-alkenes.1 These alkenes can be prepared by reaction of the lithium anion (1) of trimethylsilyldiazomethane with primary alkyl halides followed by decomposition with CuCl (86-96% yield). (E)-2-Aryl-l-trimethylsi-lylethylenes are obtained directly by reaction of trimethylsilyldiazomethane with benzylsulfonyl chlorides and triethylamine. 

Treatment of the aminoketone 243 with lithium trimethylsilyldiazomethane gave the 3-pyrroline 244 (Equation 78). Annulation of related amides provided a corresponding series of 3-pyrroline-2-ones <1996H(42)75>. Likewise, pyrroles may also be obtained upon exposure of N-substituted /3-aminoketones to lithium trimethylsilyldiazomethane <1997SL1063>. 

In the first step 21 is deprotonated with LDA to form lithium trimethylsilyldiazomethane (35), which attacks aldehyde 34 to give 36. Then 38 results via 37 by Peterson olefination under basic conditions. Next, 38 loses N2 to form carbene 39, which rearranges finally to the alkyne 40. Alkyne 22 was used without further purification in the next steps. 

A route to 3-trimethylsilyl-indazoles involves the interaction of lithium trimethylsilyldiazomethane with benzynes, generated in situ from a halo-benzene. ... 

Reaction of ketones with lithium trimethylsilyldiazomethane 2 (Peterson olefination) to give after rearrangement the homologous alkynes. 

Several reports have been published on the synthesis of indazoles. [3-i-2]-Cycloaddition of lithium trimethylsilyldiazomethane with benzynes, generated from halobenzenes 19, gave the corresponding 3-trimethylsilylindazoles 20 and 21 in various ratios <04TL1769>. These trimethylsilylindazoles could also react with aryl aldehydes in the presence of cesium fluoride to give 3-(arylhydroxymethyl)indazoles in good to moderate yields <04S1183>. 2-... 

A new two-step preparation of pyrroles from (3-amino ketones and trimethylsilyldiazo-methane was developed by Aoyama and Shioiri <97SL1063>. Treatment of the N-substituted (5-amino ketones 15 with lithium trimethylsilyldiazomethane affords the alkylidene carbene intermediates 16 which undergo intramolecular insertion to yield the 2-pyrrolines 17. In this instance, dehydrogenation to the corresponding pyrroles was accomplished using Mn02-... 

Trimethylsilyldiazomethane has been shown to have a nucleophilicity between that of silyl enol ethers and enamines in dichloromethane. Trimethylsilyldiazomethane is 1.5 orders of magnitude less nucleophilic than diazomethane and 4 orders of magnitude more nucleophilic than ethyl diazoacetate. A crystal structure of lithium trimethylsilyldiazomethane, TMSC(Li)N2, has also been obtained. ... 

Lithium trimethylsilyldiazomethane has proved particularly useful in the conversion of ketones into alkylidene carbenes, vide supra, that readily undergo 1,5 C-H insertion reactions to afford cyclopentenes (eq 56). Yields are generally good and the chemoselectivity of C-H insertion is predictable. The C-H insertion of the singlet carbene into heteroatom-bearing stereocenters proceeds with retention of stereochemistry (eqs 57 and 58). Reaction with acetals affords spiroketals (eq 59) or 2-cyclopentenones after acetal hydrolysis (eq 60). ... 

Arynes have also been reported to undergo [3+2] cycloaddihons. Indeed, a [3+2] cycloaddition reaction of lithium trimethylsilyldiazomethane [TMSC(Li)N2] with... 

The ring-opening of W-alkoxycarbonylpyroglutamic acid esters 60 by lithium trimethylsilyldiazomethane at < -100 °C afforded diazo-norleucinates 61 with minimum formation of polymeric by-products. The Wolff rearrangement of 61 in the presence of silver benzoate in aqueous dioxane at 70 °C for 6 h led to the A-Boc a-ethyl ester of a-aminoadipic acid 62. With the use of ultrasound, the reaction proceeded at ambient temperature furnishing good yields of 62a-c. ... 

Owing to the high stereospecificity of the reaction, a singlet vinylidene is thought to be the intermediate in the formation of a methylenecyclopropane by addition of lithium trimethylsilyldiazomethane to an aliphatic ketone in the presence of an alkene. ... 

Preparative Methods prepared in situ by lithiation of trimethylsi-lyldiazomethane using n-butyllithium prepared in situ by lithiation of trimethylsilyldiazomethane (TMSCHN2) using butyllithium, lithium diisopopylamide (LDA), or lithium 2,2,6,6-tetramethylpiperidide (LTMP). The lithium salt is easily converted to the corresponding magnesium bromide salt (eq 1). 

Lithium trimethylsilyldiazomethane has proved particularly useful in the conversion of ketones into alkylidene carbenes. 

The reaction of the lithium salt of trimethylsilyldiazomethane 137 with isothiocyanates affords 2-amino-l,3,4-thiadiazoles . When the reaction product is quenched with alkyl... 

Trimethylsilyldiazomethane reacts with n-butyl lithium to give Me3SiC(Li)N2, which undergoes a [3+2] cycloaddition reaction with ketenimines to give the 1,2,3-triazoles 93 in 67-82 % yields... 

From Epoxysilanes.—Epoxysilane rearrangements continue to provide useful routes to carbonyl compounds. For instance, homologation of a ketone to the corresponding aldehyde using lithium trimethylsilyldiazomethane (2) involves the intermediate formation and the subsequent hydrolysis of an a,/3-epoxysilane (3). Furthermore, it has been shown that pyrolysis of a,/8-epoxysilanes yields silyl enol ethers which, on hydrolysis, would give carbonyl compounds structurally isomeric to those which would be obtained by direct hydrolysis (Scheme 7). ... 

Metalation of diazomethane produces the lithiated compound 11a having a structure similar to 10a except for the C-Li bond in particular, the C-N and N-N bonds do not change much on metalation. Moreover, since there is no lone pair on the central nitrogen, the lithium does not bridge between C and N. In 11b the CN bond is computed to be much shorter and the NN bond much longer than in 11a, The isomeric lithium derivative 11b is computed to be more stable than 11a, The interconversion of the two isomers probably occurs via the dimers that are substantially more stable than the monomers. A crystal structure that contains the related lithiated trimethylsilyldiazomethane, (CH3)3SiCHN2, was interpreted with the help of model calculations. ... 

---