Furanyl lithium

An extension of the Barbier reaction to carboxylates salts [90] affords a simple access to furanyl ketones [91]. By sonication of a mixture of a lithium carboxylate, an alkyl chloride and lithium in THE at room temperature, the intermediate organolithium reagent forms rapidly, then generates the 2-furanyl lithium which adds to the carboxylate group in high yields. The method constitutes an example of a reaction cascade , in which several intermediates are generated sequentially (Scheme 3.13). 

In the enantiospedfic synthesis of the phospholipase A2 inhibitor (+)-(4Jl)-manoahde 71, a crucial step was the generation of the furanyl-lithium 67 by transmetalation of the parent stannane 66 with s-BuLi at —60 °C by using a mixture of Et20 and pentane as the solvent. Organolithium 67 was then reacted with cuprate 65, in turn prepared by lithiation of the homoallyhc iodide 64 foUowed by reaction with 1-pentynylcopper, to give intermediate 68. The latter underwent a... 

D-lincosaminide (22) starting from aldehyde 21, prepared in 6 steps fiom D-threonine and furanyl lithium is outlined in Scheme 8. Several unprotected aldoses (D-glucose, D-galactose, D-arabinose,... 

The method has been extended to other polyfunctionnal systems, such as O-ethyl S-(tetrahydro-2-oxo-3-furanyl)dithiocarbonate. Treatment of y-butyrolactone with bis [methoxy(thiocarbonyl)]disulfide in the presence of 2.2 equivalents of lithium diisopropy-lamide at —78 °C in THF provides the lithium enolate which reacts with MgCla to furnish the magnesium enolate (equation 17). 

We recently reported a convenient and efficient synthetic route to new 3-substituted 2,3-dihydrobenzo[h]furans 278 based on the tandem cyclization-y-alkylation of 2-bromophenyl ( )-3-phenyl-2-propenyl ether 276 whose operational simplicity could find favor in many applications161. Previous attempts using 2-bromophenyl (E)-2-propenyl ether failed because the cyclic intermediate underwent a y -elimination. We thought that a likely strategy to overcome the y-elimination in the cyclic (2,3-dihydrobenzo[h]furanyl)methyllithium intermediate could be substitution by a phenyl moiety that could provide increased resonance stabilization to the cyclic lithium intermediate 277 (Scheme 85). 

A solution of 217 mg (0.654 mmol) of lxhydroxy-2a,6/i,8j8-trimethyl-10-oxo-7j8-[2-(3-tetrahydro-furanyl)ethyl]-r/ m-bicyclo[4.4.0]decane-2/t-carboxylicacid (dehydrotctrahvdromarrubic acid) in 15 mL of methanol is added with stirring to 300 niL of liquid ammonia. 800 mg of lithium metal are added in portions over a period of 30 min, waiting after each addition until the blue color has disappeared before the addition of more of the metal. When all the lithium has been added, 15 g of ammonium chloride arc slowly added to the mixture, which is left stirring until all the ammonia has evaporated. Ice water is added to the residue and the solution is acidified with hydrochloric acid. The acidified solution is extracted with ethyl acetate, and the combined ethyl acetate fractions arc washed with sat. aq sodium chloride and dried over Nu,S04. Evaporation gives the crude product [yield 211 mg (96%)] which is recrystallizcd from ethyl acetate yield 162 mg (74%) mp 179 — 184"C mixed mp 179-181 C. 

Ketones. Sonochemical Barbier reaction allows direct access to ketones from the condensation of lithium carboxylates and organohalides in the presence of Li. An interesting approach to 2-furanyl ketones involves in situ deprotonation of furan with nascent t-BuLi (generated with the assistance of ultrasound) and subsequent reaction with RCOOLi. 

Summary Pure and mixed substituted indoyl-, pyrroyl-, and furanyl-silanes are formed in the reaction of heteroaromatic compounds with lithium alkyls and halosilanes (1-3). Chains of silyl-bridged molecules are available (7). The crystal structure of a lithium derivative (10) is presented and the 1,2-silyl group migration from nitrogen to carbon is proved. Formation of a 16-membered macrocycle (12) containing four indole molecules is described. 

Gustafsson B, Ullenius C. Asymmetric induction in the conjugate addition of lithium dioragnocuprates to (—)-menthyl 3-(2-furanyl) acrylate. Tetrahedron Lett. 1977 18 3171-3174. 

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