Solvents terminal alkyne synthesis

The synthesis of the first alkynyliodonium tosylates was achieved by the treatment of terminal alkynes with [hydroxy(tosyloxy)iodo]benzene (HTIB) (equation 8)8,10,11. Such reactions are generally conducted with an excess of alkyne in chloroform at reflux, although they can be carried out at room temperature, and dichloromethane can be employed as solvent. This procedure is, however, restricted to terminal alkynes in which R is either an aryl group or a bulky alkyl group. With linear alkyl groups (i.e. R = n-Pr, n-Bu, fl-C5Hn), phenyl(/ -tosyloxyvinyl)iodonium tosylates are obtained instead (equation 9)8. In some cases (R = /-Pr, /-Bu), mixtures of alkynyl- and (/ -tosyloxyvinyl)iodonium tosylates are produced8. ter -Butylacetylene appears to be the optimum substrate for this approach and has been employed with a series of [hydroxy(tosyloxy)iodo]arenes for the synthesis of various aryl(ter/-butylethynyl)iodonium tosylates (equation 10)9. 

During the biomimetic total synthesis of endiandric acids A-G by K.C. Nicolaou and co-workers, the key polyunsaturated precursor was assembled via the Giaser coupiing of two different terminal alkynes. " One of the alkynes was used in excess so the yield of the heterocoupled diyne could be maximized. In a solvent mixture of pyridine methanol (1 1), the two reactant alkynes were treated with Cu(OAc)2 at 25 °C to provide the desired diyne in 70% yield. 

Despite the multitude of functional groups present and the insolubility of the nucleosides in inert solvents, palladium-catalyzed coupling reactions have been used in their synthesis. Thus, the coupling of terminal alkynes with iodinated uracyl nucleosides proceeds in high yield in the presence of a Pd°-Cu catalyst in warm triethylamine, and several of the products obtained by this route have shown useful antiviral activity (Scheme... 

Hydroboration is especially valuable for the synthesis of stereodefined 1- alkenyl-boronic acids. A general method is the hydroboration of terminal alkynes with cate-cholborane 7 [16, 17] (eq (14)). The reaction is generally carried out at 70 without solvent, but it is very slow in THF solvent. More recent results demonstrate that the hydroboration of alkenes or alkynes with catecholborane is strongly accelerated in the presence of palladium [18]. rhodium [19]. or nickel catalysts [20], thus allowing the reaction to proceed below room temperature. 

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

Recently, the group of Sharpless [144,145] popularized the 1,3-dipolar cycloaddition of azides and terminal alkynes, catalyzed by copper(I) in organic synthesis. This process was proven to be very practical, because it can be performed in several solvents (polar, nonpolar, protic, etc.) and in the presence of different functions. These cycloadditions were classified as click reactions, defined by Sharpless. 

Cu(l)-modified zeolites, especially Cu(I)-USY, proved to be very efficient catalyst in multicomponent reaction. Such catalysts allowed for an efficient, solvent-free synthesis of propargylamines from aldehydes, amines and terminal alkynes with high yields. 

Schmidt R, Thorwirth R, Szuppa T, Stolle A, Ondruschka B, Hopf H. Fast, ligand- and solvent-free synthesis of 1,4-substituted Buta-l,3-diynes by Cu-catalyzed homocoupling of terminal alkynes in a ball mill. Chem Eur J 2011 17 8129-38. 

The same research group reported on synthesis of [2]rotaxane employing Diels-Alder reaction of terminal alkyne with 1,2,4,5-tetrazine to provide stopper units (Scheme 8.2) [11]. Synthetic concept is identical as in the previous example. Two components in acetonitrile after evaporation gave pseudorotaxane 9, which was subjected to ball milling with ym-tetrazine 10. After 9h, [2]rotaxane 11 was obtained in high yield. Silica gel was added to facilitate transformation in solid state. Under mechanochemical solvent-free conditions, small, but sufficiently bulky pyridazine rings were used for stoppering the pseudorotaxanes. 

Bottom-line comments. Copper-catalyzed click chemistry is experimentally too easy and works too well in most cases not to be strongly considered as a means of stitching together just about any terminal alkyne and azide. The regiospecificity for 1,4-disubstituted heteroaromatic triazoles is complemented by the corresponding ruthenium-catalyzed cycloadditions to afford 1,5-adducts. And with options for heterogeneous processes, microwave-assisted thermal rate enhancements, and solvent-free conditions, click chemistry has become, and rightfully so, a tremendously powerful tool in synthesis. 

Sharghi, H., Khalifeh, R., and Doroodmand, M. M. 2009b. Copper nanoparticles on charcoal for multicomponent catalytic synthesis of 1,2,3-triazole derivatives from benzyl halides or alkyl halides, terminal alkynes and sodium azide in water as a green solvent. Adv. Synth. Catal. 351(l-2) 207-218. 

Synthesis of Triazoles A number of MCRs that use an epoxide-azide-alkyne Cu(I)-catalyzed cycloaddition sequence to provide substituted p-hydroxy-l,2,3-triazoles 70 (Scheme 3.36) have been recently developed. The azida-tion of an epoxide with sodium azide to give 2-azidoalcohols and subsequent reaction with a terminal alkyne have been carried out under mild conditions in environmentally friendly solvents, such as water, using the catalytic system CuSO sodium ascorbate [65] (see the example depicted in Scheme 3.36) [65a] or a porphyrinatocopper(II) complex... 

D. Aguilar, M. Contel, E. P. Urriolabeitia, Chem.-Eur. J. 2010, 16, 9287-9296. Mechanistic insights into the one-pot synthesis of propargylamines from terminal alkynes and amines in chlorinated solvents catalyzed by gold compounds and nanoparticles. 

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