Bromides alkynyl

Yields of the coupling products with alkynyl bromides are relatively low as compared with those obtained with allyl chloride or benzyl chloride. One reason for this is the instability of the product. The dienediynes 51 are slowly cyclized under the influence of light to give pentacyclic dimers 52 (Eq. 2.36), one of which has been characterized by X-ray analysis. 

The second reason for the lower yields is the high reactivity of the intermediate. Two molecules of the alkynyl bromide react in a stepwise manner with the zirconacyclopentadiene. When one alkynyl halide molecule couples with the zirconacyclopentadiene, the intermediate bears a metalladienyne moiety (as in 50), as shown in Eq. 2.36... 

Eq. 2.36. Coupling reaction of zirconacyclopentadienes with alkynyl bromides. 

The coupling with alkynyl iodides in the presence of CuCl and DMPU proceeds quite differently from that with alkynyl bromides. Although the first step of the coupling is the same, the subsequent Cu/I exchange reaction of the intermediate is different. As the final product, iododienyne 54 is obtained in high yields, as shown in Eq. 2.37 [35]. In the case of alkynyl bromides, Cu/Br exchange does not proceed. Therefore, the alkenyl copper moiety couples with the second alkynyl bromide molecule. 

An unusual Sonogashira coupling between an alkynyl bromide and a 4-ethynylpyridine 142 was reported to produce a new complexing agent 143 containing a highly-conjugated pyridine subunit [116]. In addition, alkynylpyridines, as important intermediates in medicinal chemistry,... 

An entirely different situation is found in alkynyl halides. Here only examples in which the rearrangement is supported by carbonyl groups [106, 164] or electron-withdrawing pentafluorophenyl groups [165] are known. As one example, the selective reaction of the alkynyl bromide next to the carbonyl group, in the presence of a second alkynyl bromide with a propargylic C-O sigma bond, is shown (88 —> 89) [164] (Scheme 1.38). 

The corresponding propargyl sulfmates behave similarly. Compound 145 [425] (Scheme 1.65), demonstrating the principle with an interesting alkynyl bromide as the substrate, is just one of numerous examples [322, 380, 403, 423, 426-443]. 

As noted for the Heck reaction, aryl, alkenyl, and alkynyl bromides, iodides, and triflates are best for the oxidative addition. However, aromatic, heteroaromatic, alkenyl, and even alkyl boronic acids and esters can be coupled effectively. The reaction appears almost oblivious to other functional groups present ... 

It has proven possible to add oxidatively highly activated copper metal ( Rieke copper ) to alkynyl bromides in moderate yields, to furnish acetylenic copper compounds (equation 44)10. Bubbling oxygen through the system resulted in the formation of homocoupling products. 

For the preparation of the second component 421 of the cockroach pheromone Burgsthaler et al. 228) also used a Wittig reaction. Lithium acetylide is alkylated with the two halides 414 and 416 and the resulting alkynyl bromide 417 converted into the phosphonium salt. Olefination of the corresponding ylide with 9-bromo-2-nonanone 418 gives a (Z)/( )-mixture of olefin 419 which is converted into the pheromone 3,ll-dimethyl-29-hydroxynonacosan-2-one 421 by aeetoaeetate synthesis, hydrogenation, hydrolysis, and decarboxylation 228) (Scheme 73). 

The use of secondary alkynyl bromides such as 3-bromo-l-phenyl-1-butyne in this reaction leads to 5-methyl-3-phenyl-4-nitroisoxazole [518] and not 3-methyl-5-phenyl-4-nitroisoxazole [515] (Scheme 82). 

Copper(n)-catalyzed intramolecular amidation of alkynyl bromide 217 led to macrocyclic ynamide 218 in 76% yield (Equation 21) <2006JOC4170>. 

Electrophilic cyclization of a wide variety of (Z)-enynols affords substituted (Z)-5-(l-iodoylidene)-2,5-dihydrofur-ans with high regio- and stereoselectivity under mild reaction conditions. To access the cyclization precursors 27, a zirconium-mediated cross-coupling reaction of three different components involving an alkyne, a ketone, an alkynyl bromide in a one-pot procedure has been developed (Scheme 34) <2005JOC6999>. 

Cross-coupling reactions between 1-alkynyl halides and 1-alkenylboranes, which are readily available via hydroboration of alkynes, can also be catalyzed by Pd-phosphine complexes. Stereoselective synthesis of conjugated ( )-enynes 143 was achieved by the coupling of the alkynyl bromide with an alkenylborane [Eq. (48)] [69]. 

RegiocontroUed synthesis of 2,4-disubstituted pyrroles is achieved using the alkylation of a protected cyanohydrin with an alkynyl bromide (equation 15). ... 

Solutions of alkenyl- and alkynyl-zinc bromides suitable for further syntheses can be prepared from 2-alkenyl and 2-alkynyl bromides by zinc in tetrahydro-furan.141... 

G.ii. Intramolecular Addition to Alkenes and Alkynes. Organolithium reagents can react with alkenes or alkynes in an intramolecular reaction, although both are relatively inert to the analogous intermolecular reaction. Ward treated alkynyl bromide 263 with n-butyllithium and observed a 60% yield of... 

The following points should be noted (i) The yield is usually low in this reaction, mainly due to a homocoupling reaction of the 1-alkynyl bromide and polymerization, (ii) The configuration of the carbon-carbon double bond in 35 is exclusively Z (not E), indicating that the effect of the interaction between and in 26 (Scheme 11) on the stereochemical outcome is replaced by that between R and the Pd residue that is, due to the linear spatial arrangement of R, syn-26 is exclusively formed in the reaction mixture. (iii) The regioselectivity is somewhat lower however, with a less reactive nucleophile, the regioselectivity is 100% (Scheme 15). 

To clarify the mechanistic hypothesis, the authors carried out a series of experiments by treating the zirconacycle 310 with aUyl electrophiles in the absence of an alkynyl bromide (Scheme 10.104). 

The CUSO4-1,10-phenanthroline complex efficiently catalyzes amidation of alkynyl bromides to furnish ynamides, in both intermolecular and intramolecular manners (eq 25). This C-N bond forming reaction can be used for easy construction of macrocyclic ynamides (eq 26). ... 

Fu et al. developed a room temperature, photoinduced, copper-catalyzed C—N Ullmarm coupling of electrophiles with nitrogen heterocycles (229- 231).The scope of allowed electrophiles is quite broad aryl halides, including hindered and deactivated examples, alkenyl halides, and alkynyl bromides are all tolerated. Indoles, benzimidazoles, and imidazoles can all undergo C-N coupling (13JA13107). 

The benzothiazolyl alkyne 58 is typically prepared by the Sonogashira reaction of various alkynyl bromides 53 with benzothiazole 52. However, examples... 

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