Lithium acetylide reagent

A new set of carbohydrate-based thermotropic liquid crystals (17) have been prepared via reaction of the oxetan (18)(derived from glucose) with lithium acetylide reagents followed by catalytic hydrogenation. A related series of 2,5-anhydro-hexitol derivatives (19) have been prepared by a similar route, reacting the oxetan with long-chain alcohols in presence of trifluoroacetic... 

An alternate ethynylating reagent is the lithium acetylide-ethylene-diamine complex which is available commercially. This reagent in dimethyl sulfoxide solution has been used to ethynylate 11 j -hydroxyestrone and its 3-methyl ether. 

An ethynylation reagent obtained by decomposition of lithium aluminum hydride in ethers saturated with acetylene gives a satisfactory yield of (64), Best results are obtained with the lithium acetylide-ethylene diamine complex in dioxane-ethylenediamine-dimethylacetamide. Ethynylation of (63) with lithium acetylide in pure ethylenediamine gives (64) in 95% yield. 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Introduction Since we had already developed the novel asymmetric addition of lithium acetylide to ketimine 5, we did not spend any time on investigating any chiral resolution methods for Efavirenz . Our previous method was applied to 41. In the presence of the lithium alkoxide of cinchona alkaloids, the reaction proceeded to afford the desired alcohol 45, as expected, but the enantiomeric excess of 45 was only in the range 50-60%. After screening various readily accessible chiral amino alcohols, it was found that a derivative of ephedrine, (1J ,2S) l-phenyl-2-(l-pyrrolidinyl)propan-l-ol (46), provided the best enantiomeric excess of 45 (as high as 98%) with an excellent yield (vide infra). Prior to the development of asymmetric addition in detail, we had to prepare two additional reagents, the chiral modifier 46 and cyclopropylacetylene (37). 

Ethylalkynyl reagents of RC CZnEt type were prepared by Te-Zn exchange of EtjZn (1.5 equiv) with acetylenic teUuride, reagents of RC CZnEtjLi and (RC=C)2Zn type by the treatment of lithium acetylides respectively with Et2Zn or ZnCl2 (0.5 equiv). 

Sodium acetylides are the most common reagents, but lithium, magnesium and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylene diamine complex. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. 1,4-Diols can be prepared by treatment of aldehyde with dimetalloacetylenes. 

Methylmagnesium N-cyclohexyliso-propylamide, 189 with organolithium reagents f-Butyllithium, 58 Lithium acetylide, 44 with functionalized carbon reagents Alkyldimesitylboranes, 8 Di- x-carbonylhexacarbonyIdicobalt, 99... 

MICHAEL ADDITIONS Alumina. Aluminum chloride. Cesium fluoride-Silicon(lV) cthoxidc. 1,4-Diazabicyclo[2.2.2]octanc. l,8-Diazabicyclo[5.4.0]-7-undecene. Ketene r-butyldimethylsilyl methyl acetal. Lithium acetylides. (S)-( + )-2-Mcthoxymethylpyrrolidine. Methyl lithiodithioacetate. Methyl (phcnylsulfinyl)acetate. Methyl 2-trimcthylsilylacrylate. Nickel carbonyl. Organocopper reagents. 8-Phenylmcnthol. Phenyl 2-(trimethylsilyl)ethynyl sulfone. Tetra-n-butylammonium fluoride. Tiianium(IV) chloride. 3-Triisopropylsilylpropynyllithiuni. Zirconium(IV) n-propoxiilc... 

Both phenyllithium and butyllithium reacted with tetraacetyl-glucosyl bromide to yield products identical with those previously obtained with the corresponding Grignard reagents. Benzyllithium or lithium acetylide with tetraacetylglucosyl bromide resulted in intractable sirups or tars. Sodium acetylide and phenylsodium likewise led to no crystalline product. 

A more general and efficient approach to alkynyl carboxylates, also thought to involve alkynyliodonium carboxylate intermediates, entails the treatment of bis(acyloxyiodo)-arenes with alkynyllithium reagents (equation 88)81. These reactions are best conducted in the presence of 2-nitroso-2-methylpropane in order to suppress oxidative coupling of the lithium acetylides by the acyloxyiodanes. 

Alkynyl(methoxy)borates prepared in situ from an alkynyllithium or sodium and 9-methoxy-9-BBN coupled with 1-alkenyl and aryl halides (Equation (210)).899-902 Addition of triisopropylborate to lithium acetylide yielded an air stable and isolable ate complex that couples with aryl and alkenyl halides (Equation (211)).903 904 Air and moisture stable alkynyltrifluoroborates were probably the most convenient reagents that allow handling in air and coupling reactions in basic aqueous media (Equation (212)).46... 

Alkynyl sulfenylotion.x Reaction of a lithium acetylide with the adduct (a) of the reagent (1) with an alkene results in a complex mixture or an allylic sulfide. However, alkynyl sulfenylation can be effected with the ate complexes of a lithium acetylide with a thiophile. Two complexes can be used the 2 1 complex with (C2H5)2A1C1 or the 1 1 complex with A1(C2H5)3. 

Lithium acetylides 28 are oxygenated by lithium t-butylperoxide, prepared from anhydrous t-butylhydroperoxide and LHMDS, to give lithium ynolates 29 (equation 9) °. This method has been used as an efficient route for the preparation of the silyl ynolates 30" (Section V). Dioxygen, t-butyl perborate and bis(trimethylsilyl)peroxide have been unsuccessful as oxidation reagents " . ... 

Many syntheses of useful compounds utilize the nucleophilic addition of a Grignard or organo-lithium reagent to form carbon-carbon bonds. For example, a key step in the synthesis of ethy-nylestradiol (Section 11.4), an oral contraceptive component, is the addition of lithium acetylide to a ketone, as shown in Figure 20.5. 

Lithium acetylide stabilized as its ethylenediamine complex is a very effective reagent in reactions with alkyl halides . DMSO is found to be the best polar solvent for its use (80-90% yields) but DMF is also satisfactory. These solvents have the advantage that the use of the inconvenient liquid ammonia is avoided. The reaction with iodo- and bromoalkanes requires lower temperatures (8 °C) than with chloroalkanes (25-35 °C). No internal alkynes or 1,2-dienes are formed . The lithium acetylide complex has also been used in the preparation of fluoroalkynes in DMSO (e.g. equation 129) . ... 

For substituted epoxides, reagents, such as dialkynyl magnesium compounds (RC=C)2Mg [56] or lithium acetylides RC=CLi, are more effective and give better yields. 

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