From haloalkynes

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. 

SCHEME 3.149 Copper-catalyzed synthesis of ynamides from haloalkynes [166]. 

After preparation from interaction of 3-bromopropyne with copper(I) cyanide and filtration from copper salts, an explosion occurred dining distillation of the evaporated filtrate at 45-60°C/66 mbar. This was attributed to explosion of some dissolved copper acetylide(s). After refiltration the product was again distilled at 45-48°C/53 mbar without incident, and it appeared to be stable, unlike true haloalkynes. However it is undoubtedly an endothemic compound with its two triple bonds. 

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]. 

The enolates derived from racemic 2-(trimethylsiIyI)- or 2-benzyl-3-ethoxy-2,3,3a<4,7,7a-hexa-hydro-1 //-isoindol-l-one (13) react with some haloalkynes. Attack by the electrophile occurs at the bridgehead carbon (7a) from the least hindered side, to afford only one diastereomer of the alkylation product 14, as judged by spectroscopic properties14,15. In some experiments 2-desilylation is effected before product isolation15. 

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. 

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... 

An early challenge to the IIT mechanism came from Arens . It seemed important to emphasize that nucleophilic substitution at atoms other than carbon may occur especially when rather stable carbanions can be expelled . Besides the illustrations given in Table 6, the haloalkyne synthesis and its reversion (equation 245) which involve attacks on hydrogen and halogen are examples supporting his contention "... 

Although most of our information about substituent effects on RC CX in process (2) comes from qualitative experiments (Table 6), there are quantitative data for X = Cl, Br, I (Tables 24 and 25). Because of the very limited number of examples - , there is no information on how R and X affect the reactivity of a haloalkyne when is the exclusive nucleophilic target. We have noted previously that where Co is attacked, the reactivity increases as the electronegativity of X... 

Monoalkynyltitanium derivatives TiCl(C=CR)(OPr1)2 are prepared from the in situ formation of Ti(n) species and subsequent reaction with haloalkynes through an addition-/3-elimination mechanistic process, showing that this is a powerful method for the synthesis of organometallic compounds. Investigations are carried out in order to rule out the classical oxidative addition of the low-valent titanium species into the carbon-chloro bond. These complexes can further react chemoselectively with a wide range of functionalized electrophiles.21... 

The advantages of lithium acetylides over haloalkynes (in Michaelis-Arbuzov or Michaelis-Becker routes) have been clearly demonstrated in several comparable syntheses. For example, from tlie condensation of 3,3-diethoxy-l-lithio-l-propyne with diethyl chlorophosphate at -65°C, diethyl... 

Alternatively, a-chiral ketones can be prepared from dialkyl-(l,l,2-trimethylpropyl)boranes by cyanidation (method ), carbonylation (method ( )) or the haloalkyne route (method )9. 

The trialkylborane is derived from monoalkyl-(l,l,2-trimethylpropyl)borane by hydroboration. Care must be taken in the oxidation step leading to the a-chiral ketones and buffering is necessary to avoid racemization. However, even with these precautions, 2-6% racemization is observed in some cases9,20. The intermediate alkenyl-(l,l,2-trimethylpropyl)borinates are relatively resistant to oxidation thus prolonged reaction times or higher temperatures are sometimes required to complete the reaction via the haloalkyne route. 

Dihalo-l-alkenes From 1-haloalkynes, through hydroboration and treatment of the resulting 1-boryl-l-haloalkenes with CuBr2, a simple preparation is accomplished. 

Several new methods for the preparation of 1-haloalkynes have been described. High yields of bromo compounds, e.g. 28, are obtained by treatment of alkynes with triphenylphosphine/carbon tetrabromide, or with a concentrated aqueous solution of potassium hypobromite and potassium hydroxide (equation 1). 1-Iodoalkynes are produced from terminal alkynes and bis(pyridine)iodine(I) tetrafluoroborate in methanol in the presence of sodium methoxide (equation 2) or from alkynes with a mixture of iodine, potassium carbonate, copper(I) iodide and tetrabutylammonium chloride under phase-transfer catalysis. Lithium acetylides 29 (R = Ph, t-Bu, HOCH2 etc.) react with zinc iodide and bis(trimethylsilyl) peroxide to yield 1-iodoalkynes. The method has been... 

Aliphatic or aromatic aldehydes react with (ethoxycarbonyliodomethyl)triphenyl-phosphorane (183) in the presence of potassium carbonate in a two-phase liquid-solid system to give acetylenic esters 184 . Pyrolysis of a-halophosphoranes 185 (X = Cl or Br R = Ar or t-Bu) results in 1-haloalkynes 186. Vacuum pyrolysis of the betaine 188, formed from the phenoxymethylenephosphorane 187, yields the acetylenic ether 189 Flash-vacuum pyrolysis of the phosphorane 190 at 750°C gives triphenylphosphine oxide and phenylacetylene with elimination of the ethoxycarbonyl groups... 

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