Reaction with lithium acetylides

Such side reactions can be avoided by inverse addition using a large excess of the chloroformate. We have described some very successful reactions with lithium acetylides [6, 7]. Addition of solutions of 2-furyllithium and of 2-thienyllithium to a large excess of methyl chloroformate also gave good results, but a low yield of methyl benzoate was obtained with the stronger base phenyllithium [9]. 

The rate of RLi additions to methyl isothiocyanate seems to be strongly dependent upon the basicity of RLi [9]. Whereas phenyllithium reacts rapidly at — 90 °C, the addition of the much more weakly basic 2-thiazolyllithium (pK of 1,3-thiazole is about 29) has to be carried out at —30 to —50 °C and the reaction with lithium acetylides RC=CLi (pK acetylenes is 26 or lower) requires 0 to 20 °C (all reactions were carried out at the same 0.5 to 1 mol/1 concentrations). These temperatures indicate the conditions for other organolithium compounds and also the chance of success for other reactions. A rough estimation of the pK values of RH has to be made first, taking into account stabilizing effects of substituents. Side reactions have not yet been observed in the conversions of isothiocyanates with lithium compounds. 

Chloroazulenes having electron-withdrawing substituents at the 1- and/or 3-positions give abnormal products from reactions with lithium acetylide or lithium phenyl acetylide in that the new substituent appears at the 4- or 6-positions [147,148]. It is suggested that an addition-elimination mechanism is involved [147, 148], e.g. 

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

Modifying the reaction medium to involve liquid ammonia with metallic lithium, f-butyl alcohol, and white phosphorus, to which is added the haloalkane, is reported to provide the primary alkylphos-phine derived from the haloalkane.19 Similar results are reported for the reaction of red phosphorus with sodium acetylides20 and by treatment of red phosphorus with sodium metal in an organic medium followed by the addition of two equivalents of f-butyl alcohol and the haloalkane.21 The latter approach is noteworthy in that moderate yields (45%) are obtained for primary phosphines derived from secondary haloalkanes (Figure 2.6). Mixtures of tertiary phosphines bearing one or two acetylenic linkages are produced in low yield ( 15%) by the reaction of lithium acetylides with white phosphorus in liquid ammonia followed by addition of a haloalkane.22... 

Keller (1998) describes the semi-continuous reaction process of a vinyl ketone K with lithium acetylide LA to yield lithium ethinolate LE an intermediate in the vitamin production. In an undesired side reaction an oligomer byproduct BP is produced. During the process, reactant K is fed to the semi-batch reactor at a rate to maximize the selectivity for LE. 

Reaction of dianhydro alditol 84 with lithium acetylides in the presence of BF3 Et20 followed by acidic work-up and catalytic hydrogenation affords 1,2-m-C-furanosyl compounds 86100 (Scheme 28). 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

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... 

A second approach (472) to 512 started with trans-2-buitnc epoxide (524) (Scheme 67). Opening of the epoxide ring of 524 with lithium acetylide gave an acetylenic alcohol, which was converted to the acetylenic acid (525) by carbox-ylation with gaseous carbon dioxide. Partial hydrogenation of 525 followed by lactonization afforded the a,3-unsaturated lactone (526) which was transformed to the nitrolactone (527) by a Michael addition reaction of nitromethane. The Nef reaction of 527 gave the tetrahydrofuranyl acetal (528) which was converted to... 

In fact, the first isolation ofthe vinylidene pentacarbonyltungsten complexes was reported by Mayr et al. in 1984 [6]. The vinylidene complexes 16 were obtained by the alkylation of anionic pentacarbonyltungsten t-butylacetylide complex 15, obtained by the reaction of [Et4N ] [W(CO)5Cl ] with lithium acetylide, with FS03Me or [Et30 ] [Bp4 ]. Further protonation with CF3SO3H in the presence of Me4N P afforded a unique method for the preparation of carbyne complexes 17 (Scheme 5.4). 

Reaction of Lithium Acetylide with Protected 4-Bromobutanol and Subsequent Deprotectian... 

Reaction Of Acroleine and Crotonaldehyde with Lithium Acetylide in Liquid... 

The aryl sulfoxide moiety may serve as a good leaving group in the exchange reaction. Thus, 1-haloalkenyl sulfoxide 55 undergo the exchange at —78°C to give carbenoid compounds 56 which can be trapped by electrophiles or converted to acetylenes 57 (equation 39) °. Reaction of carbenoid 58 with lithium acetylides leads to the formation of enynes 59 (equation 40). ... 

Absorption of orally administered, relatively lipophilic compounds, such as estrone or estradiol, occurs mainly in the intestine. The bacteria that colonize the gut are, however, particularly adept at converting those compounds by attack at the 17 position to very water-soluble derivatives that defy absorption. Alkylation of that position avoids this catabolic pathway and consequently enhances bioavailability on oral administration. The reaction of 17-keto steroids with nucleophiles illustrates the high degree of stereospecifity that is maintained in many steroid reactions approach of that carbonyl group from the (3 face is virtually forbidden by the presence of the adjacent 18 methyl. The reaction products consequently consist of almost pure isomers from attack at the a face. Reaction of estradiol with lithium acetylide thus gives ethynylestradiol (9-2) [9] the corresponding alkylation of estradiol 3-methyl ether (9-1) leads to mestranol (9-3) [10]. Both compounds are potent orally active... 

Similarly, l-bromo-l,l-difluoro-2-alkynes, which were prepared by the reaction of lithium acetylides with CF2ClBr [284] or CF2Br2 [285], also reacted with carbonyl compounds in the presence of zinc to afford the corresponding a,a-difluoropropargyl alcohol [285]. This reaction has been utilized for the preparation of 3-fluoro-2,5-disubstituted furans [286] and other fluorinated biologically active compounds [285,287] (Scheme 99). 

Diels-Alder reactions of a -ethenylidenecyclanonesJ These dienophiles (1) are readily obtained by reaction of lithium acetylide with epoxides followed by oxidation, but tend to polymerize when heated. Fortunately catalysts, such as BF3 etherate or ZnCl2, permit Diels-Alder reactions to proceed at low temperatures. This cycloaddition provides a regio- and stereoselective route to spirocylic dienones (2) in fair to good yield. 

Longer-chain alkyl halides may not be commercially available, but they are readily made in one step from the corresponding alcohols (Larock, 1999), as are tosylates and mesylates. Similarly, longer-chain terminal alkynes are not commercially available, but can be readily made by reaction of alkyl halides with lithium acetylide-ethylene diamine complex in dry... 

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