Coupling of acetylenes and halides

Coupling of acetylenes and halides, copper-promoted, 50,100 Cuprous chloride, reaction with an organo-magnesium compound, 50,98... 

To ascertain the possibility of inserting more than one acetylenic moiety into the pyrazole ring, the replacement of two and three iodine atoms in the appropriate halides by different alk-l-ynes was carried out. To increase the total rate, the cross-coupling of diiodopyrazoles and triiodopyrazole was performed with higher initial concentrations of the reactants than for the monoiodides. The reaction of diiodopyrazoles with the acetal was completed for the most part in 40 h, and in 64 h in the case of triiodopyrazole. The yields of the di- and triacetals reached 70-90% (Table XTTT). 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

Wang et al. have discovered that ultrafme Ni powder in the presence of Cul, PPh3, and KOH promotes coupling of terminal alkynes with aryl and alkenyl iodides in high yields [65], Recent developments have shown, moreover, that the use of co-catalysts (Cu, Zn, Al, etc.) to facilitate the formation of the acetylides is not always required and that cross-coupling reactions of acetylenes and aryl halides can be performed successfully with Pd-based catalysts alone, even with difficult substrates [48, 66]... 

Repetitive coupling of acetylenes with aryl halides is an effective way to directly build hyperbranched architecture in a stepwise manner. This type of polycoupling is often catalyzed by palladium complexes in the presence of amines and has been widely used for the preparation of well-defined oligomers, linear polymers, and perfectly branched dendrimers [19,20]. 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42]. This methodology is now used widely for the constiuction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modem acetylene chemistry [44]. 

Cross-coupling of acetylenes with aryl halides E)-alkenylarenes. (E)-Atkenyl-zirconium compounds (1), obtained by hydrozirconation of terminal alkynes, react smoothly with aryl bromides and iodides in the presence of 10 mole % of Nl[P(CeH5)3]4 to form (E)-alkenylarenes (2) in yields generally of 70-95%. ... 

Cross-coupling of aryl and vinyl halides with terminal acetylenes (the Sonogashira reaction) is among the fundamental methods of Pd-catalyzed C-C bond forming reactions. Cu-Pd co-catalysis is considered a standard requirement for this method. 

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 coupling of terminal acetylenes to alkenyl bromides is illustrated by the preparation of 88 from (Zj-3-methylpent-2-en-4-yn-l-ol (8). For the preparation of 88, the compound 8 is coupled with ( )-l-bromo-2,6-dimethylhepta-1,5-diene (89) in the presence of Pd(PPh3)4/CuI [45] (Scheme 21). It should be noted that the Cul used is not esssential for the reaction, but apparently facilitates the coupling of vinyl and aryl halides to alkenes that are not electron deficient. 

The cyclization of thienyl-substituted diacetylenes with hydrogen sulfide or sodium sulfide is also a very successful method for the synthesis of oligothiophenes. The key point here is the synthesis of the precursor diynes. Symmetrical diacetylenes can be obtained by the oxidative coupling of acetylenes with copper(I) or copper(II) salts ( Glaser, Hay, or Eglington coupling ). The synthesis of unsymmetric diynes proceeds best via the Cadiot-Chodkiewicz procedure in which an acetylene is reacted with an acetylic halide in the presence of copper(I) salts [117]. Therefore, thienyl-substituted acetylenes and bromoacetylenes are important starting materials. 

The terminal diyne 320 is prepared by coupling of the zinc acetylide 318 with /rfln.s-l-iodo-2-chloroethylenc (319), followed by elimination of HCI with sodium amide[231]. Similarly, terminal di- and triynes are prepared by using cw-l,2-dichloroethylene[232]. The 1-alkenyl or l-aryl-2-(perefluoroalkyl) acetylene 321 is prepared by the reaction of a zinc acetylide with halides[233]. 

Similarly, the limitations and peculiarities of the cross-coupling of pyrazolyl-halides with terminal acetylenes have been fully and systematically studied by Russian chemists (86TH1 97TH1). 

Martin, Padron, and coworkers have reported on the scope and limitations of the use of iron(lll) halides as effective catalysts in the coupling of alkenes or acetylenes with aldehydes to achieve a wide variety of useful synthetic transformations. All these reactions are shown in Scheme 10, which serves as a guide through the aliphatic C-C bond formation section [27]. 

Cross-coupling of terminal acetylenes used as nucleophiles with aryl or alkenyl halides (referred to as the Sonogashira-Hagihara, or SH, reaction) is a versatile method of synthesis for acetylenic compounds, which are rapidly gaining importance as advanced new materials and building blocks for implementing unusual molecular architectures. 

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