Phenylacetylene, cross-coupling

It is noteworthy that the only deiodinated product (4-nitro-1,3-dimethylpyrazole) was isolated in a 70% yield (86TH1) by cross-coupling phenylacetylene with 5-iodo-4-nitro-l,3-dimethylpyrazole (Scheme 44). 

Over the last decade, the chemistry of the carbon-carbon triple bond has experienced a vigorous resurgence [1]. Whereas construction of alkyne-con-taining systems had previously been a laborious process, the advent of new synthetic methodology based on organotransition metal complexes has revolutionized the field [2]. Specifically, palladium-catalyzed cross-coupling reactions between alkyne sp-carbon atoms and sp -carbon atoms of arenes and alkenes have allowed for rapid assembly of relatively complex structures [3]. In particular, the preparation of alkyne-rich macrocycles, the subject of this report, has benefited enormously from these recent advances. For the purpose of this review, we Emit the discussion to cychc systems which contain benzene and acetylene moieties only, henceforth referred to as phenylacetylene and phenyldiacetylene macrocycles (PAMs and PDMs, respectively). Not only have a wide... 

Pd-catalyzed cross-coupling of aryl iodide 38 and terminal phenylacetylene 39 gave a dimer (e. g. 40) containing both trimethylsilyl-protected acetylene and aryltriazene moieties. 

Dipolar cycloaddition reaction of trimethylstannylacetylene with nitrile oxides yielded 3-substituted 5-(trimethylstannyl)isoxazoles 221. Similar reactions of (trimethylstannyl)phenylacetylene, l-(trimethylstannyl)-l-hexyne, and bis (trimethylsilyl)acetylene give the corresponding 3,5-disubstituted 4-(trimethyl-stannyl)isoxazoles 222, almost regioselectively (379). The 1,3-dipolar cycloaddition reaction of bis(tributylstannyl)acetylene with acetonitrile oxide, followed by treatment with aqueous ammonia in ethanol in a sealed tube, gives 3-methyl-4-(tributylstannyl)isoxazole 223. The palladium catalyzed cross coupling reaction of... 

Scheme 16.96 Cross-coupling reaction of an a-allenyl alcohol and phenylacetylene.

The use of l-iodo-9-fluorenone (59) for cross-coupling with phenylacetylene produced 60, which on treatment with 51 gave the benzannulated enyne-allenes 61 (Scheme 20.14) [43], Thermolysis of 61 in 1,4-CHD at 75 °C promoted the Myers-Saito cyclization reaction, leading to 63 in excellent yields. Again, the benzylic radical center in 62 is a stabilized triarylmethyl radical. 

The cross-coupling of 3-iodopyridine and 4-dimethylamino-phenylacetylene was reported to work efficiently in the presence of a nickel based catalyst system too (7.42.),60 The described conditions (e.g. catalyst loading, solvent, temperature, additive) are more or less the same as in the conventional palladium catalyzed variant, although the nickel based system gave only poor results with bromoazines. 

Although the Sonogashira-coupling of heterocycles is usually limited to their bromo and iodo derivatives, in certain cases the cross-coupling might also be achieved on activated chloro compounds. The chloro derivative shown in 8.23. was coupled with trimethylsilylacetylene.32 In another example the imidoyl chloride subunit of the 5-chloro-1,4-benzodiazepine derivative shown in 8.27. coupled efficiently with phenylacetylene to give the expected disubstituted acetylene derivative.15... 

Figure 4.7. Infrared spectra used to monitor cross-coupling and deprotection reactions on resin-bound phenylacetylene oligomers. Observation of a null at 3311 and 2156 cm-1 corresponds to complete acetylene coupling and trimethylsilylacetylene deprotection, respectively.

The palladium/PPFA-catalyzed asymmetric cross-coupling of a-(trimethylsilyl)-benzylmagnesium bromide 25 has also been applied to the synthesis of optically active propargylsilane 29 (18% ee) by the use of l-bromo-2-phenylacetylene as a coupling partner (Scheme 2-18) [37]. 

The chemistry used to prepare phenylacetylene dendrimers is also based on this methodology in view of the multiple conversions, a high-yielding and well-established procedure was required. The dendrimer was prepared in an elegant way by repeating the cross-coupling and deprotection using monomers such as those shown in Scheme 5-5 [58]. 

These ease of preparation of vinyl and aryl triflates and the availability of the starting materials have expanded their use as a coupling partner with a terminal acetylene. Facile Pd-Cu coupling of vinyl triflates with terminal acetylenes was reported by Cacchi [51]. The cross-coupling of enol triflate 88 with phenylacetylene proceeds easily under normal conditions [Eq. (33)] [52]. For the double cross-coupling of aromatic 1,2-ditriflates with TMSA, the addition of Bu4NI accelerates enediyne formation [Eq. (34)] [53]. 

The synthesis of derivatized, concave pyridines could be accomplished in a straightforward manner [118]. Thus, 335 could be transformed to 336 upon cross-coupling with phenylacetylene. Furthermore, the Sonogashira reaction was also able to generate dimerized variations 338 of these compounds by reacting 337 with 325. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. Heteroaryl halides like bromooxazoles are viable substrates for the Pd-catalyzed cross-coupling reactions with terminal acetylene in the presence of Pd/Cu catalyst. In 1987, Yamanaka s group described the Pd-catalyzed reactions of halothiazoles with terminal acetylenes [50]. Submission of 4-bromo- (72) and 5-bromo-4-methyloxazoles (73) to the Sonogashira reaction conditions with phenylacetylene led to the expected acetylenes (74 and 75). 

Scheme 69 Proposed mechanism of C-P bond formation in Cu-catalyzed cross-coupling of a phosphine-borane and phenylacetylene...

The cross-coupling of aryl bromides and alkynes was found to be catalyzed by Pd(0Ac)2/IMes-HCl/Cs2C03 in DMAc at 80 °C (Scheme 17). Undesired dimerization products were obtained when phenylacetylene was employed as the alkyne source. This side reaction was suppressed by using a more reactive substrate, l-phenyl-2-(trimethylsilyl)acetylene [65]. Worthy of note is that high yields of coupled products were achieved under Cu-free conditions. Addition of 2 mol% Cul increased the reaction rates, most notably with deactivated or sterically encumbered aryl bromides. The catalytic system has a limited... 

Copper Reactants. Application of the Pd/Cu-catalyzed cross-coupling, the Sonogashira reaction, with monosubstituted or protected acetylene gives rise to a variety of ethynyl-heteroarenes (Schenae 27). Reactions with trimethylsilylacetylene or phenylacetylene in... 

Phosphapalladacycles stabilized by highly hindered phosphines showed very good catalytic activity in the copper-free cross-coupling of aryl bromides with phenylacetylenes in NEts with a maximum TON of 8000. 

Scheme 9.9 Water-soluble tris(guadinophenyl)phosphine 22 and triphenylphosphinetrisulfonate trisodium salt (26) used to cross-couple anionic p-iodobenzoate 23 with propiolate 24 to give phenylacetylene 25 in aqueous media [67dj.

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