Lithium diisopropylamide-Chlorotrimethylsilane

Silylnitronates 1 are prepared14-24,25 by metalation of primary nitroalkanes with lithium diisopropylamide and treatment of the lithionitronates with either chlorotrimethylsilane or (/er/-butyldimethyl)chlorosilane. Nonaqueous workup and distillation gives the silylnitronates in >75% yield as moisture sensitive, but thermally stable, products. (e/7-Butyldimethylsilylni-tronates are more stable than the corresponding trimethylsilyl compounds. 

The first reference to 2-trimethylsilyloxy-l,3-butadiene (1) was a report2 of its reaction with tetracyanoethylene by Cazeau and Frainnet without mention of any experimental details. Later, Conia3 reported its synthesis in 50% yield with only a reference made to the usual House procedure4 for silyl enol ethers. The diene 1 has also been prepared using lithium diisopropylamide as base and chlorotrimethylsilane in tetrahydrofuran-ether (1 1) in yields up to 65%, but on a smaller scale.s... 

At this point, consideration was next accorded to proper introduction of the pair of substituents as in 34. As expected, the regiocontrolled introduction of a methyl group proved not to be problematic, and lithium diisopropylamide came to be favored as the base. The p isomer 29 predominted by a factor of 5 1 over the a isomer for the usual steric reasons (Scheme 5). To reach silyl enol ether 31, it was most efficient and practical to react the 29/30 mixture with chlorotrimethylsilane under thermodynamic conditions. This step proved to be critical, as it allowed for implementation of the Lewis acid-catalyzed acetylation of 31 under conditions where the benzyloxy substituent was inert. Equally convenient was the option to transform the modest levels of enol acetate produced competitively back to starting ketone by saponification with methanolic potassium hydroxide. 

Oxidative 1,3-coupling of dicarboxylic esters via treatment with lithium diisopropylamide in the presence of chlorotrimethylsilane gave bis-silylenol ethers, which on reaction with tita-nium(IV) chloride produced cyclopropanedicarboxylic esters 11 in moderate yield.It is assumed that initial conversion to an enoxy radical takes place via a titanium enolate, followed by a diradical 1,3-coupling. 

Unquestionably, the most attractive procedure for the preparation of dialkyl l-(trimethylsilyl)meth-ylphosphonates is the carbanionic route. The obvious transmetallation difficulties occurring when carbanionic reagents are employed in conjunction with activated methylene groups have led to the development of procedures based on the trapping of a-metallated phosphonates with chlorosilanes in the presence of lithium diisopropylamide (LDA) in excess. For example, the addition at -70°C of chlorotrimethylsilane (1 eq) to a solution of dialkyl 1-lithioalkylphosphonates prepared from dialkyl alkylphosphonates (1 eq) and LDA (2 eq) produces, after workup, dialkyl l-(trimethylsilyl)alkylphos-phonates in 75-90% yields of isolated product, via the quantitative and clean generation of stable dialkyl l-lithio-l-(trimethylsilyl)alkylphosphonates (Scheme Varying the phosphorus reac-... 

The introduction of bromo substituents can convert the commercial 1,2,3-trifluorobenzene into useful building blocks (Scheme 1-2). Consecutive treatment with 5ec-butyllithium and elemental bromine gives l-bromo-2,3,4-trifluorobenzene (1, 95%). l,5-Dibromo-2,3,4-trifluorobenzene (2, 87%) forms when the silane obtained by in situ trapping of 5-bromo-2,3,4-trifluorophenyllithium with chlorotrimethylsilane is heated in the presence of elemental bromine. Upon incubation with lithium diisopropylamide, a basicity gradient-driven heavy halogen migration occurs to provide an intermediate that affords with tetrabromomethane or methanol l,2,3-tribromo-4,5,6-trifluorobenzene (3, 67%) and l,2-dibromo-3,4,5-trifluorobenzene(4,92%), respectively. 

A solution of 2-methylcycloheanone (11.2 g, 100 mmol) in THF (10 mL) is added to a stirred solution of lithium diisopropylamide [prepared in situ by addition of a 1.6-M solution of -butyllithium (66 mL, 106 mmol) in hexane to diisopropylamine (16.8 mL, 120 mmol) in dry THF (240 mL) at -78 C] under a nitrogen atmosphere at -78 °C over 10 min. The solution is stirred for a further 1 h, then chlorotrimethylsilane (22 mL, 170 mmol) is added over 5 min. The solution is allowed to warm to rt and, after being stirred for 1 h, the solvent is evaporated in vacuo. Dry pentane (100 mL) is added and LiCl thus precipitated is removed by filtration. The filtrate is concentrated in vacuo, refiltered (if necessary), and distilled (bp 59-61 °C at 7 mmHg) to give the title compound in 97% yield. ... 

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