Bromoalkynes, terminal alkynes

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 ... 

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... 

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]. 

Whereas Glaser-type oxidative coupling opens efficient synthetic pathways toward symmetrical diynes, its performance in heterocoupling is poor. The latter may be accomplished by Cadiot-Chodkiewicz coupling of terminal alkynes with 1-haloalkynes (usually 1-bromoalkynes). The reaction is conducted in the presence of an amine and catalytic amounts of a copper(I) salt. Because, in contrast with the Glaser-type reactions described above, it follows a nonoxidative reaction mechanism, oxygen is not necessary - but needs often not to be excluded (Scheme 4) [9]. 

As a last example of an uncatalyzed C,C coupling of a neutral organocopper compound Figure 16.9 depicts the alkynylation of a copper acetylide with a bromoalkyne which is easily accessible via bromination of a terminal alkyne ... 

For the preparation of conjugated alkynes, one can alkenylate or arylate alkynes according to Section 13.3.4. Alternatively, metallated alkenes or metallated aromatic compounds also may be alkynylated, but this option will not be pursued further. We merely mention in passing that bromoalkynes and iodoalkynes are suitable alkynylat-ing agents and that these can be obtained in a one-step reaction from terminal alkynes ... 

The coupling of a terminal alkyne with a 1-bromoalkyne in the presence of a copper(i) salt and an amine base (B), referred to as the Cadiot-Chodkiewicz coupling , is of particular synthetic importance because of the facile roiite it provides to unsymmetrical polyacetylenes with an even or odd number of triple bonds (equation 10). The reaction has been reviewed and these reviews should be... 

The reaction is carried out by slowly adding the 1-bromoalkyne to a solution containing the terminal alkyne, amine, copper(i) chloride and hydroxylamine hydrochloride. The amine, usually ethylamine, is used in excess, e.g. 1-8 moles/mole of alkyne, and catalytic quantities (1-5 mol %) of copper(i) chloride are used. One of the side-reactions is the self-coupling of the bromoalkyne induced by Cu(i) which in turn is oxidized to Cu(ii) (equation 11). The hydroxylamine salt serves to reduce the copper back to the cuprous state. 

Tlie cross-coupling of a terminal alkyne 9 with a 1 -bromoalkync 8 in the presence of an aliphatic amine and a catalytic amount of a Cu(I) salt affords unsymmetrically substituted diynes [10, Eq.(5)]. This useful reaction, discovered by Cadiot and Chodkiewicz [8], can be employed advantageously for the synthesis of several polyunsaturated systems. Generally the bromoalkyne is introduced dropwise to a mixture of the alkyne, ethylamine, and MeOH or EtOH in the presence of a catalytic amount of CuCl, and a small amount of NH OH-HCl. The reducing agent, NHjOH-HCl, is used to reduce the copper(TI) ion. The alkynylcopper(I) is assumed to be the reactive intermediate. The formation of the symmetrical diyne can be suppressed by maintaining the concentration of the bromoalkyne. This side reaction is particularly significant in the case of less acidic alkynes such as alkylalkynes [9J. 

The heterocoupling of a terminal alkyne with a 1-bromoalkyne in the presence of an aliphatic amine and a catalytic amount of a copper(I) salt affords unsymmetrically substituted diynes (2 equation 5). This useful reaction, discovered by Chodkiewicz and Cadiot, can be employed advantageously for the synthesis of several polyunsaturated systems. 

Monoalkylbromoboranes hydroborate terminal alkynes to yield alkylalkenylbromoboranes, which then rearrange to yield (Z)-alkenes after protonation this useful procedure has been applied to the preparation of muscalure (35 Scheme 35). ( -Alkenes are available by a similar sequence if 1-bromoalkynes are employed at the hydroboration stage. Similarly, dialkenylthexylboranes yield dienes on rearrangement and protonation. ... 

An original, and versatile route toward ulosonic acids has been recently elaborated by Wu et al. [103,104,105], It based on a simple introduction of a-keto acid moiety via propargylation of suitable monosaccharides derived aldehydes and subsequent oxidation of the terminal alkynes. As it is exemplified by preparation of KDO, coupling of 61 with 3-bromopropyne gave the a fr-adduct 139 (Scheme 30). Its bromination using NBS/AgNC>3 provided the bromoalkyne 140, which on reaction with KMnC>4 afforded the desired a-keto acid ester, easily convertible into the anomeric mixture of KDO derivatives 143. The yield of all intermediates were very high. 

Treatment of dibromoalkene with a lithium base (BuLi or LDA) generates a bromoalkyne intermediate via dehydrohalogenation, which undergoes metal-halogen exchange under the reaction conditions and yields the terminal alkyne upon workup. 

Copper tends to form more stable organocopper compounds with acetylene compounds than with aryl compounds. The synthetic reaction of acetylenic compounds with copper or copper salt, e.g., the Cadiot-Chodkiewics and Glaser reactions are well known. The Cadiot-Chodkiewics reaction is a reaction where I-bromoalkyne easily reacts with a terminal alkyne in the presence of a catalytic amount of a cuprous salt or amines to afford conjugate diacetylene compounds in high yield [43]. For example, polyacetylene is easily synthesized as shown in eq. (22.19) [43],... 

For the synthesis of nonsymmetrically substituted 1,3-butadiynes the Cadiot-Chodkiewicz coupling is usually apphed [30, 31]. In this protocol a terminal alkyne is reacted with a terminal bromoalkyne derivative in the presence of a Cu(i) salt and an amine. As examples we show in Scheme 7.3 the synthesis of the l-azacydotetradeca-3,5,10,12-tetrayne derivatives 10(3)a to 10(3)f [32], 1-isopropyl-l-azacydopentadeca-3,5,ll,13-tetrayne (10(4)(c)) [33] and 1-isopropyl-l-azacydo-hexadeca-3,5,12,14-tetrayne (10(S)(c)) [33]. 

In addition to the silver-promoted chemistry, gold compounds have shown a propensity to catalyze the conversion of terminal alkynes into bromoalkynes (Scheme 7.156) [252]. The authors screened a range of catalysts for activity towards the halogenation reaction and found that BUjPAuNTf was the most active. The conditions for this reaction were mild (room temperature), and the yields were outstanding (up to 95%). 

Bromoalkynes from Terminal Alkynes. Terminal alkynes on reaction with Ph3P and CBt4 afford 1-bromoalkynes in high yield (eq 17). ... 

Dibromoborane-dimethyl sulfide exhibits high reactivity toward internal alkynes . The relative reactivity of 1-octene, 1-hexyne, (Z)-3-hexene and 3-hexyne is 100, 290, 20 and 5900, respectively. This makes possible selective hydroboration of internal alkynes in the presence of terminal unsaturation. With 1-bromoalkynes Br2HB SMe2 provides [Z]-l-dibromoalkenylboranes which can be transformed into [E]- or [Z]-l-alkenylboronic esters . 

A recent convenient method for the preparation of 1-bromoalkynes in excellent yields (>90%) consists in the treatment of terminal acetylenes with the triphenylphosphine/tetra-bromomethane bromination reagent [81], In a further new development, 1-bromo- and 1-iodoacetylenes 137 are obtained by reacting trimethylsilyl-protected alkynes 136 with either N-bromo- (NBS) or 7V-iodosuccinimide (NIS) in the presence of silver nitrate [82] [Eq. (23)]. 

Iridium dimer complexes catalyse the 3 + 2-cycloaddition reactions of organic azides with bromoalkynes to furnish 1,5-disubstituted 4-bromo-1,2,3-triazoles in excellent yields under mild conditions. Ruthenium(II)-azido complexes undergo 3 + 2-cycloaddition reactions with strained cyclooctynes under ambient temperatures. No reaction was observed with non-activated terminal or internal alkynes under the same conditions. Dithioic acid copper catalysts (60) catalyse the 3 + 2-cycloaddition reaction of azides with alkynes to form 1,4-disubstituted-1,2,3-triazoles in various solvents and under various temperatures. Thermal Huisgen 3 + 2-cycloaddition reactions of azides and bis(trimethylsilyl)acetylene formed 4,5-bis(trimethylsilyl)-l/f-l,2,3-triazoles in low to high yields (15-95%). The Cu(I)-catalysed 3 + 2-cycloaddition... 

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