1-Bromoalkynes

TABLE XVII. Examples of Alkynylpyrazoles Prepared from 1-Bromoalkynes (99USP5925769). 

The two reactions described above can be applied for the synthesis of symmetrical -acetylenes only. Unsymmetrical bis-acetylenes can be prepared by using the Cadiot-Chodkiew icz reaction For that method a terminal alkyne 1 is reacted with a bromoalkyne 8 in the presence of a copper catalyst, to yield an unsymmetrical coupling product 9 ... 

Zf-Alkenes can be prepared by several related reactions.29 Hydroboration of a bromoalkyne generates an a-bromoalkenylborane. On treatment with methoxide ion these intermediates undergo B C migration to give an alkyl alkenylborinate. Protonolysis generates an Zi-alkene. 

For the development of the oxidative homocoupling reaction, in 1955 Chodkiewicz and Cadiot explored a Cu(I)-catalyzed heterocoupling reaction of terminal alkynes with 1-bromoalkyne in the... 

Recently, Marino et al. reported a Cadiot-Chodkiewicz cross-coupling reaction of bulky trialkylsilyl-protected alkynes with 1-bromoalkynes in aqueous amine to form a variety of unsymmetrical diynes in good yields (75 95%) (Eq. 4.23).44... 

Methylenetetrahydrofurans can also be realized by an intramolecular radical cyclization of bromoalkynes utilizing indium(I) iodide as a radical initiator <06TL2859>. 3-Diiodomethylenetetrahydrofurans were also prepared from l,to-diiodo-l-alkynes in the presence of l-hexynyllithium<06CC638>. 

Bromoalkynes also couple with vinylstannanes readily to result in enynes. Synthesis of protected enynals via cross-coupling of vinylstannanes with 1-bromoalkynes in the presence of a catalytic amount of Pd(II) has been reported (equation 143)252. Hiyama and coworkers extended the Stille methodology for sequential three-component coupling of trimethylstannyl(trimethylsilyl)acetylene with a vinyl iodide in the first step and cross-coupling of the intermediate trimethylsilylethyne with another alkenyl iodide in the presence of tris(diethylamino)sulphonium trimethyldifluorosilicate in the second step to generate a dienyne (equation 144)253. Both steps occur under palladium catalysis, in one-pot, to result in stereodefined l,5-dien-3-ynes. 

Trialkylvinylstannanes react with 1-bromoalkynes, as shown in reaction 48... 

Bromoalkynes reacting with two equivalents of tributyltin hydride exclusively provide the E-isomer ... 

Disubstituted alkynes and terminal alkynes form E-dibromoalkenes [4] when the tribromide is formed in situ in an essentially basic medium, an addition reaction followed by elimination of hydrogen bromide results in the conversion of terminal alkynes into the 1-bromoalkynes [5]. When the addition reaction is conducted in methanol, l,l-dibromo-2,2-dimethoxyalkanes are produced, in addition to the 1,2-dibromoalkenes [6], The dimethoxy compounds probably result from the initial intermediate formation of bromomethoxyalkenes. Under similar conditions, alkenes yield methoxy bromo compounds [7]. 

Chloropyridinecobaloxime(III) 279 also serves as a convenient source of nucleophilic cobalt, and as a means of promoting radical cyclizations [77]. For example, its reduction in the presence of a bromoalkyne such as 280 leads to the formation of a radical 281 which closes onto the alkyne, leading eventually to the ,Z-alkenes 283 and 284 in an 81% yield. Cyclizations of this type are obviously complementary to those effected using tributyltin hydride. 

Copper iodide acts as an efficient reagent for the nucleophilic displacement of 1-haloalkynes. It transforms 1-bromoalkynes (72) into 1-iodoalkynes (73) which, on further treatment with copper(II) bis(arenesulfinate), are converted into the corresponding alkynyl aryl sulfones (74). An electron transfer between 1-haloalkynes and copper(I) salts is believed to take place for the copper-assisted halogen-exchange reaction at the acetylenic carbon atom. 

Vinylic cyanocnprates, prepared from vinylic tellnrides, react with bromoalkynes giving conjugated (Z)-enynes and (Z)-enediynes." ... 

Reaction with bromoalkynes (typicalprocedure)." The butyltelluroenine (R, = n-meth-... 

The bromoalkyne can undergo a subsequent addition of bromine. This reaction can be largely avoided by adding bromine at a sufficiendv low rate and low temperature. This further reaction with bromine is much more serious during the brominadon of lithiated enynes RCH=CHC=CLi, which gives yields of only some 60%. 

A small, high-boiling residue, presumably the adduct of Bio and the bromoalkyne is left behind. 

The bromination with alkali hypobromite in aqueous solution gives good results with (hetero)arylacetylenes, enynes (RCH=CHOCH) and diynes (RC=CC=CH) all acetylenes that are more acidic than those acetylenes in the aliphadc or cycloaliphatic series with an isolated triple bond. For the conjugated systems the hypobromite method is superior to the reaction of metallated acetylenes with bromine. Various acetylenic alcohols are also brominated smoothly, which can be explained in part by their better solubility in water. Since in the case of primary and secondary ethynyl alcohols, oxidation of the alcohol can occur, the use of an excess of hypobromite should be avoided. The best procedure is drop wise additon of a small shot measure of hypobromite ro a mixture of alcohol and water. If the bromoalkynes to be prepared are not too volatile, small amounts of THF or dioxane may be added to effect a better solubility of the alkyne in the aqueous phase. Addition of a co-solvent may also be desired when the starting compound is a solid (e.g. ethynylcyclohexanol). 

A convenient and quick way to prepare 1-bromoalkynes consists of adding an ethereal solution of cyanogen bromide to a strongly cooled solution of a metallated (Li or MgX) [119] acetylene in an organic solvent (EtjO or THF). The method seems very general and excellent yields can be obtained provided that the ethereal solution of BrC N (which is prepared from an aqueous solution) is dried well. The advantage of this method over the introduction with elemental bromine is that CC double bonds in the acetylenic compounds do not react... 

This side-reaction is most serious in the case of acetylenes RC=CH with a relatively low acidity aliphatic 1-alkynes, e.g. 1-octyne, and acetylenic alcohols HCaC(CH2)nOH with n > 2, give reduced yields (40-50%) in the coupling reaction. In many other reactions, yields are high. Since the bromoalkyne usually has the highest "added value", economical considerations prescribe the use of an excess of the free acetylene, especially when it is inexpensive, e.g. propargyl alcohol. The mechanism of the Cadiot-Chodkiewicz reaction has not been studied in detail, but is seems likely that a copper acetylide ROCCu is formed first it often appears as a yellowish suspension. 

Preparation or Alkynenitriles from 1-Bromoalkynes and CopperfI) Cyanide... 

Preparation of Alkynenitriles by Reaction of l-Bromoalkynes with Copperd) Cyanide in the Presence of Lithium Bromide... 

Alkynyl iodides and bromides react smoothly with various zinc-copper organometaUics at — 60 "C leading to polyfunctional aUcynes. lodoalkynes, such as 296, react at very low temperature, but lead in some cases to copper acetylides as by-products (1/Cu exchange reaction). 1-Bromoalkynes are the preferred substrates. Corey and Helel have prepared a key intennediate 297 of the side chain of Cicaprost by reacting the chiral zinc... 

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