Disubstituted acetylenes

The regioselectivity of the reaction appears to be determined by a balance of electronic and steric factors. For acrylate and propiolate esters, the carb-oxylate group is found preferentially at C3 of the carbazole product[6-8]. Interestingly, a 4-methyl substituent seems to reinforce the preference for the EW group to appear at C3 (compare Entries 4 and 5 in Table 16.2). For disubstituted acetylenic dicnophiles, there is a preference for the EW group to be at C2 of the carbazole ring[6]. This is reinforced by additional steric bulk in the other substituent[6,9]. 

The reaction can be performed under a variety of conditions. Origin-aiiyi2o,i26,234 acetylene and potassium in liquid ammonia were used. Subsequently, this was simplified by the use of potassium r-amylate in r-amyl alcohol and later this system was found to react selectively at C-17 in the presence of an A-ring a,j5-unsaturated ketone. A closer investigation of these reaction conditions revealed the formation of a small amount (2-3 %) of the disubstituted acetylene this can be avoided by reacting the 17-keto steroid with acetylenedimagnesium bromide in ether-tetrahydrofuran (see chapter 10.)... 

The condensation of 4-ethynyl-1,3-dimethyl-5-aminomethylpyrazole with iodo-benzene in the standard conditions of the Heck-Sonogashira reaction caused no complications and the yield of disubstituted acetylene was 87% (86TH1) (Scheme 68). 

Such an easy isomerization of acetylenylbenzoic acid amides implies the formation of a five-membered nonaromatic ring condensed with the pyrazole ring. However, the pyrazole analog of o-iodobenzamide (amide of 4-iodo-l-methylpyrazole-3-carboxylic acid) formed under heating with CuC=CPh in pyridine for 9 h only the disubstituted acetylene in 71 % yield is identical in all respects to the compound obtained from the corresponding acid by successive action of SOCI2 and NH3 (90IZV2089) (Scheme 126). 

Unsaturated substituents of dioxolanes 36-38 and dioxanes 39-41 are prone to prototropic isomerization under the reaction conditions. According to IR spectroscopy, the isomer ratio in the reaction mixture depends on the temperature and duration of the experiment. However, in all cases, isomers with terminal acetylenic (36, 39) or allenic (37, 40) groups prevail. An attempt to displace the equilibrium toward the formation of disubstituted acetylene 41 by carrying out the reaction at a higher temperature (140°C) was unsuccessful From the reaction mixture, the diacetal of acetoacetaldehyde 42, formed via addition of propane-1,3-diol to unsaturated substituents of 1,3-dioxanes 39-41, was isolated (74ZOR953). 

A useful self-terminating catalyst system (77), employs a Pd catalyst [prepared from Pd(OAc)2, NaH, and r-AmOH in THF]. The solvent required for the hydrogenation depends on the acetylene structure monosubslituted acetylenes require solvents such as hexane or octane, whereas disubstituted acetylenes need ethanol, ethanol-hydrocarbon, or ethanol-THF mixtures. In all cases it was necessary to use quinoline as a catalyst modifier. The authors consider this system one of the best for achieving both high yield and stereoselectivity. 

Olefins, reaction with nitrones, 46,130 cjs-Olefins f lom disubstituted acetylenes by selective reduction v ith modi fied palladium (Lindlar) catalyst, 46,92... 

Verification of the molecular weight of thiirene dioxides by mass spectrometry, employing the conventional electron-impact (El) ionization method, has been unsuccessful due to the absence or insignificant intensity of molecular ion peaks in their mass spectra. The base peak is rather characteristic, however, and corresponds to the formation of the disubstituted acetylene ion by loss of sulfur dioxide91 (equation 3). 

The regiochemistry of Al-H addition to unsymmetrically substituted alkynes can be significantly altered by the presence of a catalyst. This was first shown by Eisch and Foxton in the nickel-catalyzed hydroalumination of several disubstituted acetylenes [26, 32]. For example, the product of the uncatalyzed reaction of 1-phenyl-propyne (75) with BujAlH was exclusively ds-[3-methylstyrene (76). Quenching the intermediate organoaluminum compounds with DjO revealed a regioselectivity of 82 18. In the nickel-catalyzed reaction, cis-P-methylstyrene was also the major product (66%), but it was accompanied by 22% of n-propylbenzene (78) and 6% of (E,E)-2,3-dimethyl-l,4-diphenyl-l,3-butadiene (77). The selectivity of Al-H addition was again studied by deuterolytic workup a ratio of 76a 76b = 56 44 was found in this case. Hydroalumination of other unsymmetrical alkynes also showed a decrease in the regioselectivity in the presence of a nickel catalyst (Scheme 2-22). 

Internal RC=CR Symmetrically disubstituted acetylenes such as tolane PhC=CPh react with complex 1 by substitution of the bis(trimethylsilyl)acetylene with formation of the metallacydopentadiene 7 [2a,2d],... 

Two groups simultaneously found that trimethylsilyl cyanide reacts with disubstituted acetylenes in the presence of a Pd catalyst to form silylated 2-amino-5-cyanopyrroles 194 or 195 [133, 134], These reactions are run neat and a variety of Pd species are successful in this transformation [133]. In the case of unsymmetrical diaryl acetylenes, the reaction is not regioselective [134],... 

Thus the compound which is formally equivalent to the iron violet and black salts, Fe3(CO)8(Ph2C2)2, has a totally different structure. Compound (II) is considered to involve a six-membered osmacyclic structure, with one of the CO groups incorporated as a ketonic group. For the monoacetylenes, RC=CH (R = Me, Et, f-Bu, Ph), the reaction occurs with high yields (—20-50%) while disubstituted acetylenes, RCsCR1 (R = Ph, R1 = Me, Et) give low yields (<3%). As may be expected for unsymmetrically substituted acetylenes, three isomers of the osmacyclic ring are possible, and these are normally observed in approximately equal concentrations (136). 

The formation of meso-dimethylsuccinic acid from dimethylmaleic acid and the racemic mixture from dimethylfumaric acid implies that both hydrogen atoms add to the same side of the unsaturated molecule 11). Bourguel (12) also noted that disubstituted acetylenes yielded initially cis-ethylenes but that trans isomers were formed if the hydrogenations were protracted. 

The addition of (TMS)3SiH to a number of 1,2-disubstituted acetylenes has also been studied [25]. Yields varied from moderate at room temperature to good at 90 °C (Reaction 5.20). The shielding effect of substituents X is the major contribution for the observed stereoselectivity. 

Harwood and co-workers (105) utihzed a phenyloxazine-3-one as a chiral derived template for cycloaddition (Scheme 4.50). An oxazinone template can be formed from phenylglycinol as the template precursor. The diazoamide needed for cycloaddition was generated by addition of diazomalonyl chloride, trimethyl-dioxane-4-one, or succinimidyl diazoacetate, providing the ester, acetyl, or hydrogen R group of the diazoamide 198. After addition of rhodium acetate, A-methylmaleimide was used as the dipolarophile to provide a product that predominantly adds from the less hindered a-face of the template in an endo fashion. The cycloaddition also provided some of the adduct that approaches from the p-face as well. p-Face addition also occurred with complete exo-selectivity. Mono- and disubstituted acetylenic compounds were added as well, providing similar cycloadducts. 

Hlasta and Ackerman (72) reported a synthesis of the triazoles 379, related to the human leuokocyte elastase inhibitor WIN 62225 (380), based on an inter-molecular 1,3-dipolar cycloaddition of the azide 378 with alkynes (Scheme 9.72). They also investigated in detail the effect of steric and electronic factors on the regioselectivity of the cycloaddition reaction. (Azidomethyl)benzisothiazolone (378) underwent smooth 1,3-dipolar cycloaddition with various disubstituted acetylenes to give the corresponding triazoles (379) in 37-84% yields. Electron-deficient acetylenic dipolarophiles reacted more rapidly with the azide to give the respective triazoles. 

Mono- and disubstituted acetylenic amides can be obtained in high yields by reacting metallated acetylenes with isocyanates and dialkylcarbamoyl chloride [95-98] ... 

Acetylene and its derivatives can be polymerized by chain growth in the presence of suitable transition metal catalysts to give high molecular weight (MW) polymers (Equations (l)-(4)). The monomers include acetylene, mono- and disubstituted acetylenes, and a,tv-diynes. The polymers possess carbon-carbon alternating double bonds along the main chain and exhibit unique properties (e.g., metallic conductivity) that are not expected with vinyl polymers. 

Mo catalysts are uniquely effective in the polymerization of S-containing disubstituted acetylenes. Though there is a possibility that S and O in the monomer deactivate group 5 and 6 transition metal catalysts, the basicity of S is weakened by the conjugation with the triple bond, resulting in the lower coordinating ability to the propagating... 

Since only Ta and Nb catalysts, which are not tolerant to polar groups, are available for the polymerization of disubstituted acetylenes, it is generally difficult to synthesize disubstituted acetylene polymers having such a highly polar substituent as a hydroxy group. Recently, synthesis of poly[l-phenyl-2-( -hydroxyphenyl)acetylene] has been achieved by the polymerization of 1-phenyl-2-(p-siloxyphenyl)acetylene and the subsequent acid-catalyzed deprotection reaction. 

Rh complexes are examples of the most effective catalysts for the polymerization of monosubstituted acetylenes, whose mechanism is proposed as insertion type. Since Rh catalysts and their active species for polymerization have tolerance toward polar functional groups, they can widely be applied to the polymerization of both non-polar and polar monomers such as phenylacetylenes, propiolic acid esters, A-propargyl amides, and other acetylenic compounds involving amino, hydroxy, azo, radical groups (see Table 3). It should be noted that, in the case of phenylacetylene as monomer, Rh catalysts generally achieve quantitative yield of the polymer and almost perfect stereoregularity of the polymer main chain (m-transoidal). Some of Rh catalysts can achieve living polymerization of certain acetylenic monomers. The only one defect of Rh catalysts is that they are usually inapplicable to the polymerization of disubstituted acetylenes. Only one exception has been reported which is described below. 

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