Acetylenes reagents

Stmctural variations of the reagents used in these reactions have been a primary source of progress in dye synthesis. Acetylenic reagents for cyanine dye synthesis include the weU-known acetylenic quartemary salts as general electrophilic reagents for the preparation of carbocyanine dyes. A number of tautomeric pairs of acetylenic dyes have been prepared and their tautomeric equiUbria determined (dyes (26a), (26b)) (29). 

Chiral modification of diorganomagnesium compounds with the dilithium salt oi (S)-l,l -bi-naphthalene-2,2 -diol gave reagents with the empirical formula 30. Good to excellent enantiose-lectivities were observed in addition reactions of aliphatic and aromatic reagents to aromatic aldehydes30,31, however, the selectivities were not satisfactory with allylic, vinylic and acetylenic reagents. 

Ethynyl compounds react with sugar lactones to give acetylenic lactols (16,63). Reaction of 2,3-O-isopropylidene-D-ribonolactone (16a) with lithium acetylenic derivatives gave l-(2-substituted ethynyl)-2,3-0-isopropyli-dene-D-ribofuranoses. Similarly, treatment of 2,3 5,6-di-O-isopropylidene-L-gulono-1,4-lactone (9b) with various lithium acetylenic reagents gave... 

The synthetic method (b) combines the formation of a primary or secondary alkynol [from formaldehyde or an aldehyde respectively and an organometallic acetylenic reagent (Section 5.4.2, p. 532)] with the semihydrogenation of the triple bond to a double bond. As noted in Section 5.2.2, p. 493, appropriate selection of catalyst is necessary in the hydrogenation step to ensure the formation of either the ( )- or the (Z)-isomer. The specific formation of the allylic alcohol, CH2=CH-CH(OH),R, is from a vinylmagnesium halide (Expt 6.41) and an aldehyde. 

On the other hand, the reaction of acetylenic reagent 149 with f-BuLi gives 150 which, followed by reaction with 151, gives substituted cyclopentanes 152 in high yield and stereocontrol87 (Scheme 48). The preponderance of the li-alkene is consistent with the accepted yyw-carbolithiation mechanism. 

CHj) and several oxa- and ihia-derivatives (X - O, S). In this case, the preferred direction of attack is usually A, regardless of the substituent s position, type of amino group, and homo- or heterocyclic ring, the only exceptions being those of the lithium-acetylene reagent with dimethylaminomethyl cyclohexanone derivatives. 

A review of the methods for the generation of cyclic carbonyl ylides from intramolecular carbene additions has recently appeared [64]. This intermediate was first exploited as the An component for cycloaddition reactions by Ibata [65]. ort/io-Disubstituted carboalkoxy aryl diazoketones such as 54 were decomposed by copper complexes, generating six-membered ring carbonyl ylides. These transient intermediates underwent subsequent intermolecular cycloadditions in the presence of ethylenic and acetylenic reagents to give predominantly exo products containing the oxabicyclo[3.2.1] nucleus, Eq. 38. 

The trimethylsilyl (TMS) group from the acetylenic reagent is retained in the alkenylated product. Deprotection to a derivative with a free acetylenic group is achieved by dilute aqueous methanolic KOH. In an alternative method for acetylene protection, 2-methyl-3-butyn-2-ol has been used. 

Compared nth ynanines, which have also been applied to peptide synthesis, push-pull-acetylenes are much more selective. They do not show the side reactions observed with ynamlnes, and the yields are not markedly influenced by the sequence of addition of compounds in the activation step or by excess of acetylene reagent. 

The palladium-copper-catalyzed cross-coupling of acetylenic systems with aryl halide has been used successfully to homopolymerize p-bromoethynylbenzene (eq 4) [8]. The poly-p-ethynylbenzene was isolated as a white pol3nmer of relatively low molecular weight. The coupling of acetylenic reagents with aryl halides has been noted to lead to explosions and therefore due care should be exercised. 

The structure of the condensation products of thioureas and dimethyl acetylenedicarboxylate had not been assigned with certainty. This problem has now been resolved, in one case, by 2f-ray analysis. Thus the addition of iV-thiocarbamoylpiperidine to the acetylenic reagent, which may theoretically give rise to six isomeric products, yields in fact 5-methoxy-carbonylmethylene-2-piperidino-2-thiazolin-4-one, having the geometrical configuration shown in (166). Confirmation has also been provided that the reaction of thiourea with bromosuccinic, maleic, fumaric, or acetylenedicarboxylic acids yields, in each case, a 2-thiazoIine, e.g. (167). ... 

Enzymes capable of generating a carbanion or a carbanion-like intermediate adjacent to an acetylene are susceptible to irreversible inhibition by these acetylenic reagents. Flavin-linked and pyridoxal-linked enzymes and isomerases have proved to be good candidates for inhibition by the acetylenic inhibitors. This is the case because these enzymes are generally involved in C—bond abstraction with concomitant carbanion or car-banion-Iike intermediate formation. However, the critical factor is the formation of a free valance adjacent to the acetylenic imit. An enz3rme that could do so is a candidate for inhibition by these inhibitors. Thymi-dylate synthethase, for example, should be irreversibly inhibited by 5-ethynouracil the free valance would be generated adjacent to the acetylene by means of an enzyme-catalyzed nucleophilic addition to the uracil. ... 

This reaction proceeded at the AChE active site with nearly complete syn- or 1,5-selectivity, controlled by the topology of the narrow gorge. Strikingly uniform sy -selectivity was obtained for enzyme-produced triazoles, independently of the linker length and stereochemistry of the acetylene reagent. 

For direct alkynylation with TIPS-acetylene, a hypervalent iodine TIPS-acetylene reagent can also be used as demonstrated in Waser s recent works. Alkynylation on C-3 of indole was catalyzed by AuCl (eq 26) and the Wacker cyclization s intermediate was intercepted by the hypervalent iodine TIPS-acetylene (eq 27).2 ... 

A variety of stable five-coordinate organozirconocene-ate complexes, including 57 and 58, have been prepared and structurally characterized. The reaction process was based on both (i) the nucleophilic attack of tertiary phosphines on acetylenic reagents and (ii) the ability for 16-electron d -zirconocene(IV) complexes to coordinate two-electron donor ligands. The nature of the heteroelement directly bonded to the triple bond of the terminal acetylenic system directs the nucleophilic attack of the phosphine in all cases only one regioisomer was observed. ... 

Action of Acetylenic Reagents. Isothiazoline-5-thiones (39) react rapidly with acetylenic reagents e.g. dibenzoylacetylene) to form mono-adducts of type (40). A-Phenylmaleimide gives an adduct, but diethyl azodicarboxylate gave only... 

Equimolar quantities of acetylenedicarboxylic acid esters (166) and 2-N-substituted l,3-dithiolan-2-imines (169) undergo a 1,3-dipolar cycloaddition, with elimination of ethylene, to yield A -thiazoline-2-thiones (168). The same products result from 2-alkylthio-l,3,4-thiadiazoline-5-thiones (167), with loss of alkyl thiocyanate as shown. They are desulphurized to the corresponding thiazolinones (172) by the action of mercuric acetate in acetone-acetic acid. They react with two further moles of the acetylenic reagent (166) to produce the spiranes (170 e.g. = R = COzMe), which are in turn desulphurized and cleaved by Raney nickel to the AMhiazoline derivatives (171). An analogous series of reactions was carried out using propiolic acid esters. ... 

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