Lithium acetylide ethylenediamine complex

Both sodium acetylide in xylene (Air Reduction Corporation) and lithium acetylide-ethylenediamine complex (Foote Mineral Co.) are now commercially available, and have been used successfully for the ethynylation of 17-keto steroids. 

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). ... 

A. 1 -Phenyl-3-butyh-1 -ol (1) (Note 1). A 1000-mL, oven-dried, three-necked, round-bottomed flask is equipped with a magnetic stir bar and pressure-equalizing addition funnel, fitted with a rubber septum, and placed under an argon atmosphere. The flask is charged with lithium acetylide-ethylenediamine complex (50 g, 543 mmol) (Note 2), which is dissolved in anhydrous dimethyl sulfoxide (360 mL) (Note 3) with stirring. The flask is placed in a room temperature water bath (Note 4), the addition funnel is charged with styrene oxide (42.0 mL, 368 mmol) (Note 5), and styrene oxide is added dropwise over a period of approximately 5 min. The reaction mixture is stirred for 2 hr and quenched by... 

Lithium acetylide-ethylenediamine complex was purchetsed from the Aldrich Chemical Company, Inc., and used as received. 

Lithium acetylide-ethylenediamine complex Ethylenediamine, compd. with lithium acetylide (Li(HC2)) (1 1) (8) 1,2-Ethanediamine, compd. with lithium acetylide (Li(HC2)) (1 1) (9) (6867-30-7)... 

Commercial Lithium Acetylide-Ethylenediamine258 Lithium acetylide-ethylenediamine complex (122 g) is added rapidly with stirring under acetylene to a suspension of 13/ -ethyl-3-methoxygona-2,5(10)-dien-17-one (186 g) in dimethylacetamide (6.1 liters). After stirring for 2 hr, the mixture is cooled to 10°, ice water (12 liters) is added, and the mixture extracted with benzene. The crude product is triturated with ice cold methanol to afford, after filtration and drying, 13/2-ethyl-17a-ethynyl-3-methoxygona-2,5(10)-dien-17/ -ol (157 g) mp 130-136°. The mother liquors yield a second crop (10 g) mp 130-136°. 

It has been found that monosubstituted acetylenes can be obtained by Brown s method (equation 164) only when lithium acetylide is replaced by the lithium acetylide-ethylenediamine complex. High yields of terminal alkyl and cycloalkyl-acetylenes are obtained. It has also been demonstrated that the migration of an alkyl group proceeds with retention of configuration, as shown in equation (168). ... 

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... 

Lithium acetylide, ethylenediamine complex is purchased from Aldrich Chemical Company, Inc. and used without purification. 

Treatment of 75 with lithium acetylide ethylenediamine complex afforded the acetylene derivative 78 (85%), which was transformed into the vinyl alcohol 79 by partial hydrogenation using Lindlar catalyst. Employing the Mitsunobu reaction, compound 79 was transformed into the phthalimide 80, which was converted into the benzamide 82 (64%) via the primary amine 81 by sequential deacylation and benzoylation. When the... 

The Dias approach involves the use of three very efficient Evans oxazolidinone-mediated syn-aldol condensations. The other key steps involve a coupling reaction between the lithium acetylide-ethylenediamine complex and a tosylate followed by a methylation and a selective reduction to establish the C12-C13 (E) double bond. 

The absolute stereochemistry of the C-12 and C-13 oxirane moiety of laureoxolane (157), a colorless unstable bromoether obtained from extracts of Laurencia nipponica, was determined on the basis of a chiral synthesis of 156, a degradative derivative of 157. The C-5 to C-8 unit with two asymmetric centers at C-6 and C-7 of 157 corresponds to (25, 35)-l-benzyloxy-3,4-epoxy-2-butanol (142). Elongation of 142 using butyllithium and copper cyanide followed by the creation of a new epoxide provides 152. Lithium acetylide ethylenediamine complex addition to 152 and subsequent ketalization affords the acetylenic acetonide 153, which is coupled with (2i ,35)-l,2-epoxy-3-benzoyloxypentane (154) to furnish 155. Subsequent five-step transformation of 155 provides 156 [60] (Scheme 37). 

An organometallic approach to 938, in which there is an acetylenic—vinylidene rearrangement of a chiral jS-hydroxylactone without loss of stereochemical integrity, provides an interesting alternative to the synthesis of this natural product. Treatment of 40, derived from 39, with 2.2 equivalents of lithium acetylide-ethylenediamine complex provides crystalline diol 939 in 57% yield. However, this synthesis is problematic, because 40 is not easily prepared or isolated. A more practical route involves in situ generation of the bis-mesylate 39 and trapping with lithium acetylide-ethylenediamine complex to afford 939 in 87% overall... 

A. Tributylethynylatannane, An oven-dried, 2-L, three-necked, round-bottomed flask equipped with a mechanical stirrer, 100-mL addition funnel, and a nitrogen inlet is charged with 24.0 g (0.26 mol) of lithium acetylide, ethylenediamine complex (Note 1). The system is evacuated, placed under nitrogen, and 800 mL of tetrahydrofuran (Note 2) is added to the system via a cannula. The flask is cooled in an ice water bath and 70.7 g (0.22 mol) of tributyltin chloride (Note 3) is added dropwise over 45 min. The ice bath is removed and the mixture is stirred for 18 hr at room temperature. The flask is placed in an ice water bath and excess lithium acetylide is hydrolyzed with 20 mL of water. The reaction mixture is concentrated under reduced pressure and washed with hexane (3 x 50 mL). The organic layers are combined and dried over anhydrous magnesium sulfate. Filtration and evaporation of the solvent at reduced pressure gives a colorless oil. Distillation yields 21.4-24.3 g (31-35%) of tributylethynylstannane, bp 90-94 C (0.5 mm) as a water-white liquid (Notes 4-6). 

Lithium acetylIde, ethylenediamine complex Ethylenediamine, compd. with... 

The mesylate-tosylate in the framework of the pyranose derivative reacted with lithium acetylide-ethylenediamine complex to give the seven-membered sultone (13) in 98% yield, as a result of displacement of a tosylate coupled with deprotonation at the mesylate producing a nucleophile and then ring formation (Scheme 6) <81CJC260>. 

A full report has been published on the preparation and synthetic applications of the acetylenic dianions (35) of note here is their use in the preparation of allene-l,3-dicarboxylic acids (36). Kolbe co-electrolysis of 5-alkynoic adds, RC=C(CH2)3C02H, with half-esters of diadds Me02C(CH2) C02H followed by saponification gives the coupled product (37) in 45—50% yield. Alternative conditions have been reported for the preparation of oi-acetylenic acids from o>-iodoacids (esp. from fatty acids) using the lithium acetylide-ethylenediamine complex in HMPA. ... 

The synthesis of lithium acetylide-ethylenediamine complex has been reported it is a white, free-flowing powder that is safe and stable up to about 45°C. This complex reacts with ketones to give excellent yields of ethynyl carbinols. The complex can either be prepared or obtained from a commercial source. 

---