Diethyl lithiated carbons

A solution of 0.10 mol of lithiated methoxyallene in about 70 ml of hexane and 50 ml of THF (see Chapter II, Exp. 15) was cooled to -40°C. Ory, pure acetone (0.12 mol) was added dropwise during 10 min, while keeping the temperature at about -30°. Five minutes after the addition 100 ml of saturated NHi,Cl solution, to which 5 ml of aqueous ammonia had been added (note 1), were run in with vigorous stirring. The product was extracted three times with diethyl ether. The combined organic solutions were dried over potassium carbonate and subsequently... 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

A completely different approach to lithium homoenolate synthons uses a carbon-oxygen bond cleavage. Lithiation of acrolein diethyl acetal 180 with lithium and a catalytic amount of DTBB (2.5%) in the presence of different carbonyl compounds in THF at 0°C gave, after final hydrolysis, the corresponding y-products 181 in different diastereomeric ratios (Z/ 3/1 to 20/1) (Scheme 63) . 

Gramme is a common precursor for indol-3-ylmethylation of enolates and other nucleophiles. Such reactions normally occur by an elimination-addition mechanism. Following development of procedures for 4-substitution via directed lithiation with l-(tri-/w-propylsilyl)-gramine, Iwao and Motoi have developed conditions for tandem nucleophilic substitution of the dimethylamino group. Quatemization followed by reaction with a nucleophile in the presence of TBAF leads to alkylation. <95TL5929> The carbon nucleophiles which were successfully used include nitromethane, methyl acetoacetate, diethyl malonate and diethyl 2-(acetamido)malonate. Phthalimide, thiophenol, TMS-CN and TMS-Nj were also used as sources of nucleophiles. 

Diethyl phenylselanylmethanephosphonate can be metalated with n-BuLi in THF at -78°C. The lithiated phosphonocarbanionic species led to the corresponding a-chloro-a-phenylselanylphosphonate after treatment with carbon tetrachloride [61] (Scheme 47). The carbanion derived from the ethyl a-chloro-a-selanylphosphonate was used in a Horner-Emmons olefination with ketones to give a-chlorovinylphenyl selenides. 

For lithiated allylic phosphonates, the nature of the carbon substituent affects the regioselectivity of the initial silylation as well as the reactivity of the resulting silylated anion.Whereas diethyl... 

The reaction between lithiated diethyl propenylphosphonate and ethyl propenoate leads to carbon-carbon bond formation involving either C(i) or C(3) of the phosphonate ester. Thus, ethyl but-2-enoate or but-3-en-2-one yielded 481 and 482, respectively, and the esters 483 were obtained from coumarin, all by simple addition, but addition-elimination and multiple addition processes were also described. 

The synthesis of A/-substituted 5-trifluoromethylimidazole-4-phosphonates was reported by Yuan (Scheme 61) [76]. Addition of lithiated species, derived from diethyl isocyanomethylphosphonate using n-BuLi, to A-substituted trifluoroaceti-midoyl chloride gave an imine intermediate which underwent intramolecular cycli-zation to furnish regioselectively the 5-(trifluoromelhyl)imidazole-4-phosphonate. The addition of an enamine to the isocyano carbon under these conditions, especially without any catalytic assistance, was driven by aromatization. However, replacement of n-BuLi with NaH was ineffective and produced an inseparable complex mixture. 

Phenyllithium is known to form, in equilibrium with the monomer, a dimer 25 (Scheme 1-21) held together by electron-deficient partial bonds. However, phenyllithium can also adopt the structure of a lithium lithiate ion pair 26 (Scheme 1-21). What makes the difference The solvent plays a capital role. As long as the solvation forces remain moderate as in diethyl ether, the doubly carbon-lithium-carbon bridged dimer 25 is energetically most favorable. In a 2 1 mixture of cylohexane and diethyl ether, phenyllithium even assembles a tetrameric cluster. " " in neat THF, the four-centered dimer 25 is found in equilibrium with the monomer. " However, in the presence of the powerful electron-donor hexamethylphosphoric triamide (HMPA), it is the ion pair 26 that coexists with the monomer. Analogous lithiate complexes have been identified with... 

Various [l- C]carboxylic acids have been prepared by carboxylation of carbanions stabilized by -I or -M substituents. The examples in Figure 5.7 have been selected here as prototypes, since they are of strategic interest. Deprotonation of diethyl methylphos-phonate (18 with n-BuLi followed by [ CJcarboxylation and esterification with diazoethane provided triethyl phosphonoll- Clacetate (19) in an overall radiochemical yield of 62%. Compound 19 has been widely exploited for chain extensions by a labeled two-carbon unit via its alkenylation reaction with carbonyl compounds (Homer-Wadsworth-Emmons reaction). Similarly, reaction of alkyl halides, tosylates or carbonyl compounds with LiC = CH or LiC=CH H2NCH2CH2NH2 followed by deprotonation and [ C]carboxylation of the resulting terminal alkynes has been used as a strategic tool for the incorporation of a labeled three-carbon unit, as exemphfied in a steroid platform (20 to 21). This chemistry provides outcomes complementary to those using [ C2]acetylene (Chapter 8, Section 5.1). Finally, the [ CJcarboxylation of lithiated dimethylsulfide provided an alkylthio[l- C]acetic acid 22 and thence a functionalized 2-alkylthio[l- C]ethyl derivative 23 useful, in this case, for elaboration into e.p. 

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