Haloalkynes reactions

Cis-olefins or cis./rjns-dienes can be obtained from alkynes in similar reaction sequences. The alkyne is first hydroborated and then treated with alkaline iodine. If the other substituents on boron are alkyl groups, a cis-olefin is formed (G. Zweifel, 1967). If they are cir-alkenyls, a cis, trans-diene results. The reactions are thought to be iodine-assisted migrations of the cis-alkenyl group followed by (rans-deiodoboronation (G. Zweifel, 1968). Trans, trans-dienes are made from haloalkynes and alkynes. These compounds are added one after the other to thexylborane. The alkenyl(l-haloalkenyl)thexylboranes are converted with sodium methoxide into trans, trans-dienes (E. Negishi, 1973). The thexyl group does not migrate. 

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

The propensity of organotin hydrides for SET reactions has been utilized to initiate radical chain reactions. Anodically promoted oxidation of Ph3SnH to [Ph3Sn] at 0.80 V (vs SCE) initiates the cyclization of several haloalkyne and haloalkene ethers as well as of some fi-lactam derivatives. The catalytic cycle shown in Scheme 1 is based on... 

The reaction of haloalkynes with one equivalent of 1 affords alkynyltitanium compounds by f5-elimination from the (q2-haloalkyne)Ti(OiPr)2 intermediate, as shown in Scheme 9.5, thus providing an easy access to functionalized alkynyltitaniums [26], When this reaction is carried out in the presence of excess 1, a tri-titanated alkene of the type shown in Scheme 9.5 is generated in excellent yield. This is an interesting method for generating the permetallated terminal alkene [27]. 

The direct reduction of haloalkynes using either mercury or vitreous carbon as the cathode has been examined in considerable detail [80-84] one example is portrayed in Eq (77). The influence of reduction potential, current consumption, proton donor, electrode, and substrate concentration on the course of the process has been examined. Vitreous carbon electrodes are preferred, though mercury has been used in many instances. Unfortunately, these reactions suffer from the formation of diorganomercurials. While both alkyl iodides and bromides can be used, the former is generally preferred. Because of their higher reduction potential, alkyl chlorides react via a different mechanism, one involving isomerization to an allene followed by cyclization [83]. 

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. 

Addition-elimination (for the chloro compound) and elimination-addition (via an intermediate haloalkyne, for the bromo and iodo compounds) mechanisms account for the activation parameters determined for reaction of 2-(/3,/3-dihalovinyl)-5-nitrothiophenes with MeONa-MeOH. °°... 

Aminocarbonylation has been combined with the Pauson-Khand reaction to construct fused tricyclic alkaloid skeletons (see 00154). The tandem aminocarbonylation/Pauson-Khand reaction of haloalkynes with a chiral allylic amine promoted by Co2(CO)8 gave angular triquinanes as exemplified in Scheme 25. Thus, the reaction of l-chloro-2-phenylethyne 175 with Co2(CO)8 at 0°C gave alkyne-dicobalt complex 176, which was converted to enoyl-dicobalt complex 177 upon warming to 25 °C. The reaction of enoyl-dicobalt complex 177 with cyclopente-nylmethyl(l-phenylethyl)amine 179 yielded Pauson-Khand reaction product, angular triquinane 180, via A -allylic aminocarbonylated alkyne-dicobalt complex 178 (Scheme 25). ... 

The outstanding chemical characteristic of alkenyl halides is their general inertness in SN1 and SN2 reactions. Thus chloroethene fails to react with silver nitrate in ethanol (i.e., low SN1 reactivity), fails to react with potassium iodide in acetone (i.e., low SN-2 reactivity), and only reacts slowly with sodium hydroxide to give ethyne (low E2 reactivity). The haloalkynes, such as RC=C—Cl, are similarly unreactive. 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

Haloalken-l-yl)dialkylboranes, synthesis, 9, 195—196 Halo-alkyl compounds, with Ti(IV), 4, 349 Haloalkynes, in Cadiot-Chodkiewicz reaction, 11, 19 Haloarenes... 

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 already mentioned, there have been few mechanistic examinations of the copper-catalyzed Cadiot-Chodkiewicz heterocoupling reaction. Kinetic studies with the less reactive chloroalkynes [11a] have led to the assumption, shown in Scheme 7, that coupling between alkynes and haloalkynes proceeds through initial formation of copper(I) acetylides, probably formed by an acetylenic activation process similar to that described above for oxidative homocouplings. Subsequently, two reaction pathways may be reasonable ... 

Nonoxidative Heterocoupling of Terminal Alkynes with Haloalkynes Cadiot-Chodkiewicz Reaction... 

The pathway followed by the reaction is depicted in Figure B4.1. Methoxide anion adds to the a-haloalkenylborane generated by hydroboration of the haloalkyne, and induces migration of an alkyl group from the boron atom to the alkenyl carbon atom. The migration displaces halide anion from the alkenyl carbon atom and the centre is inverted. Finally protonolysis of the carbon-boron bond by acetic acid releases the (/f)-alkcne. 

Iodine, bromine, and chlorine react with silver acetylides to give haloalkynes. An early report of such a reaction was applied to the first synthesis of perchloropheny-lacetylene (Scheme 1.58).130,131... 

The radical intermediates from Cr(II) reduction of alkyl halides can in principle be used synthetically, but have only seen limited attention to this point. co-Haloalkynes (bromides, iodides), in the presence of excess Cr(C104)2, undergo cyclization reactions to form exo-alkylidene cycloalkanes (equation 176)347. These reactions proceed by the radical cyclization of intermediate 42 onto the alkyne unit, which undergoes subsequent reduction by Cr(II) to give a hydrolytically unstable vinylchromium(III). Rings of four, five and six members can be formed. Alternatively, a-iodo esters undergo intramolecular atom transfer radical cyclizations onto alkynes or alkenes with catalytic or stoichiometric amounts of... 

Few examples are known in which acetylenic ethers have been incorporated into benzan-nulation products [46]. Propargyl ethers have been reported to afford variable amounts of indenes and furans depending on the carbon chain [47]. Other heteroatoms that support the benzannulation reaction when adjacent to the C=C bond in the allcyne are boron (see Section 8.3.6), silicon, and tin (see Section 8.3.3). Haloalkynes give only inseparable product mixtures. 

More often such bromo- and iodoalkynes are employed with another synthetic goal in mind, namely, in the Cadiot-Chodkiewicz reaction for the formation of symmetric or asymmetric 1,3-diynes by reaction of the haloalkyne with a terminal alkyne (Figure 13.25). Additional reagents essential for the success of this reaction are one equivalent or more of an amine and a substoichiometric amount of Cul. As with the Cacchi and Stephens-Castro coupling reactions of Section 13.3.4, a Cu-acetylide is the reactive species in the Cadiot-Chodkiewicz coupling. It is formed in step 1 of the mechanism illustrated in Figure 13.25. 

Z)-vinylic tellurides are the source of enynes 212 and enediynes 213 by transformation into vinylcopper species (Section 9.13.8.2.4), followed by reaction with haloalkynes (Scheme 113).278,279 The transformation occurs with retention of the double-bond stereochemistry. This is an efficient and straightforward route to important unsaturated units present in natural products, specially in enediyne antibiotics.280... 

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