Phenylacetylene unsymmetrical

Whereas cyclotrimerization of phenylacetylene with uncomplexed PdCl2 provides only low yields of the unsymmetrical trimer, and polymers, on treatment of 3-hexyne with Pd/C and Me3SiCl 14 hexaethylbenzene 2165 is obtained in quantitative yield [78] (Scheme 13.23). 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

Melinger JS, Pan YC, Kleiman VD, Peng ZH, Davis BE, McMorrow D, Lu M (2002) J Am Chem Soc 124 12002-12012 Optical and photophysical properties of light-harvesting phenylacetylene mono-dendrons based on unsymmetrical branching... 

Another problem with this method of synthesis is that unsymmetrical acetylenes can, and usually do, give two isomeric triazoles (Scheme 2). The sterically less hindered isomer is by no means always the major product In addition to phenylacetylene, for example, the 5-phenyl-triazole often predominates in the product mixture. 

With unsymmetrically substituted mesoionic 1,3-dithiolones (2) and alkynes, the cycloaddition reactions normally yield the two possible isomeric thiophene derivatives. Thus methyl propiolate reacts with (2a) to produce an 81 19 ratio of the two possible isomeric thiophenes (88) and (89) in 90% yield, whereas the same reaction with the isomeric 1,3-dithiolone (2b) yields the thiophene derivatives in a 30 70 ratio (99%) (78CB2028). A further example is provided by the reaction of phenylacetylene with (2a) which proceeds with formation of the thiophene isomers (90) and (91) in an 89 11 ratio however, in the case of (2b) and the same substrate, the product isomer ratio is completely reversed (11 89) (78CB2028). 

If the diene fragment of the 2-pyrone and the acetylene dienophile are unsymmetrically substituted, the formation of two isomeric benzene products is possible. The model reaction between 4,5,6-triphenyl-2-pyrone (20) (XXIII) and phenylacetylene yields approximately equal amounts of 1, 2, 3, 4-(XXV) and 1,2,3,5-tetraphenylbenzene (XXVI). Therefore, this position isomerism would be expected to materialize during polymer formation when similar bispyrone monomers are polymerized with diethylnylbenzene. 

In the addition to unsymmetrical acetylenes the orientation is controlled by electronic effects. Thus, while in the reaction of phenyl azide with phenylacetylene the two isomeric diphenyltriazoles 252 and 253 were obtained in almost equal amounts , methyl propiolate yielded mainly l-phenyl-4-carbomethoxy-1,2,3-triazole (254) and only minor amounts of the isomeric 255 °. Dimethylaminoacety-lene yielded l-phenyl-5-dimethylamino-1,2,3-triazole (256) as the sole product... 

Dendrimers consisting of phenylacetylene moieties exist as (i) compact or extended meta-conjugated phenylacetylene (PA) dendrimers [40-54], and (ii) unsymmetrical branched phenylacetylene dendrimers [55-58]. 

Scheme 12 Structures of unsymmetrical phenylacetylene dendrimers 26a-d by Peng and coworkers [55-58]...

Under the reaction conditions, phenylacetylene was found to be a much more reactive coupling partner than arylboronic acids in the analogous Suzuki-Miyaura coupling, as in addition to the desired product (38), alkynylation and further addition reactions occurred with a variety of transient palladium(II) species (Scheme 27). Despite these undesired side reactions, Catellani was able to fine-tune the reaction conditions to form predominantly product 38 or 39. The formation of the desired product 38 (and suppression of product 39) is promoted by acceleration of norbomene carbopalladation by KOAc [47] and by using an excess of alkyl halide affording several structurally similar unsymmetrical alkyne products in good yields (Scheme 28). 

Dalla Croce and La Rosa examined the 1,3-dipolar cycloaddition reactions of unsymmetrical munchnones with terminal alkynes to give pyrroles 156 and 157 (Table 4.8). The reaction is generally regioselective the major pyrrole isomer from the monosubstituted munchnones have adjacent hydrogens, irrespective of the munchnone substituent. With the disubstituted munchnones, the major regioisomer is derived from attachment of C-4 of the munchnone and the p-carbon of the alkyne, except for phenylacetylene, which shows the opposite regiochemistry. The authors interpreted this behavior as a consequence of the electron-rich nature of phenylacetylene as a dipolarophile with a larger LUMO coefficient on the a carbon. 

The data shown in Table 6.3 show no obvious trends that may shed light on the mechanism(s) of the metathesis reactions. In terms of overall relative reactivity (krei of Table 6.3), phenylacetylene reacts fastest and pent-l-yne is the most sluggish alkyne, while ethyne and the parasubstituted phenylacetylenes are unreactive under the experimental conditions used. When the branching ratios and the relative reaction rates are combined, the alkyne - nitrile chaimel is the most productive for propargyl alcohol and phenylacetylene and least productive for pent-2-yne and pent-l-yne. The sterically congested alkyne exhibits modest reactivity for the metathesis reaction. No obvious relationship exists between the structure of the alkyne substrate and the propensity for a metathesis reaction. With regard to which metathesis reaction is favored for unsymmetrical alkynes, while no regioselectivity operates for pent-2-yne and phenylacetylene other terminal acetylenes favor the loss of the more substituted nitrile (Eq. (6.131)). 

Regioselective Friedel-Crafts reaction with unsymmetrical alkynes was reported. A reaction of phenylacetylene with p-xylene afforded gem-diarylethylene (71) selectively (Equation 30) [35]. Zirconium triflate showed much higher catalytic activity than that of chloride. Hf-catalyzed reaction of benzene with 1-phenylpropane in ionic liquid produced 1,1-diphenylpropene (72) in excellent yield with excellent regioselectivity (Equation 31) [36]. 

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