Alkylation reactions alkynes

Reactions that attach alkyl groups to molecular fragments are called alkylation reactions One way m which alkynes are prepared is by alkylation of acetylene... 

Alkyl-substituted alkynes can react by either the Adg3 or the Adg2 mechanism. The Adg3 mechanism leads to and addition. The preference for one or the other mechanism depends on the individual stmcture and the reaction conditions. Added CP promotes the Adg3 mechanism and increases the overall rate of reaction. 

For alkyl-substituted alkynes, there is a difference in stereochemistry between mono-and disubstituted derivatives. The former give syn addition whereas the latter react by anti addition. The disubstituted (internal) compounds are considerably ( 100 times) more reactive than the monosubstituted (terminal) ones. This result suggests that the transition state of the rate-determining step is stabilized by both of the alkyl substituents and points to a bridged intermediate. This would be consistent with the overall stereochemistry of the reaction for internal alkynes. 

The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

This scheme represents an alkyne-bromine complex as an intermediate in all alkyne brominations. This is analogous to the case of alkenes. The complex may dissociate to a inyl cation when the cation is sufficiently stable, as is the case when there is an aryl substituent. It may collapse to a bridged bromonium ion or undergo reaction with a nucleophile. The latta is the dominant reaction for alkyl-substituted alkynes and leads to stereospecific anti addition. Reactions proceeding through vinyl cations are expected to be nonstereospecific. 

Thomson Click Organic Interactive to use a web-based palette to predict products for alkyne alkylation reactions. 

Alkynes react with electrophilic selenium reagents such as phenylselenenyl tosylate.155 The reaction occurs with anti stereoselectivity. Aryl-substituted alkynes are regioselective, but alkyl-substituted alkynes are not. 

After alkylation, the alkyne triple bond can be used in other reactions ... 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

However, it is evident that Bi(III) salts have a unique activation mode and a strong Lewis acidic behavior. In this context, Bi(III) salts are well known for being capable of activating both a-donors such as alcohols or amines and Ji-donors such as alkenes and alkynes. This fact makes Bi(III) a versatile Lewis acid for various alkylation reactions in which both alcohols and C-C multiple bonds can be utilized as an electrophilic component. 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

Despite these favorable results, the Pd-catalyzed lactonization with alkyl-substituted alkynes generally gives unattractive mixtures of five- and six-membered lactones. In marked contrast, the Pd-catalyzed reaction of alkynylzincs with (Z)-/J-iodoacrylic acid gives only the expected enynoic acids135, which can then be selectively lactonized to give either five- or six-membered lactones136 (Scheme 41). 

Alkylation of Alkynes. Organic halides can alkylate acetylenes in the presence of Lewis acids. In most cases, however, the products are more reactive than the starting acetylenes. This and the ready polymerization of acetylenes under the reaction conditions result in the formation of substantial amounts of byproducts. Allyl, benzyl, and tert-alkyl halides giving stable carbocations under mild conditions are the best reagents to add to acetylenes.44 56... 

A convenient approach to synthesize novel selenium-(3-lactams, namely 3-selena-l-dethiacephems 200, was accomplished via the regioselective iodocycli-zation reaction (Scheme 73) [103]. The key starting materials, alkyne-selenoureas 201, for this approach were readily prepared by the A-alkylation reaction of the corresponding previously known propargyl-azetidinones with a wide variety of isoselenocyanates under basic conditions. First, the reaction of (3-alkyne-selenourea... 

The amide ions are powerful bases and may be used (i) to dehydrohalogenate halo-compounds to alkenes and alkynes, and (ii) to generate reactive anions from terminal acetylenes, and compounds having reactive a-hydrogens (e.g. carbonyl compounds, nitriles, 2-alkylpyridines, etc.) these anions may then be used in a variety of synthetic procedures, e.g. alkylations, reactions with carbonyl components, etc. A further use of the metal amides in liquid ammonia is the formation of other important bases such as sodium triphenylmethide (from sodamide and triphenylmethane). 

Alkylation of alkynes. The reaction of alkynes with carbonyl compounds in lolucne-aqueous NaOH is markedly accelerated by catalytic amounts of tetra-n-butylammonium bromide. 

Exo cyclisations of vinyllithiums onto phenyl-substituted alkynes 392 and 394 are also syn stereospecific, and give the sort of stereodefined dienes 393 and 395 of value in Diels Alder reactions.180 6-Exo cyclisations are also possible but are much slower, though they still give geometrically pure products (in contrast to 6-exo cyclisations onto silyl alkynes see below). Vinyllithiums cyclise onto alkyl-substituted alkynes (such as 396) only in the presence of TMEDA, and they do so very slowly. Nonetheless, a single geometrical isomer of the product 397 is obtained. 

The only functional group is the triple bond, and we shall want to use the chemistry of alkynes to show us where to disconnect. You know that alkylation of alkynes is a reliable reaction, so a sensible disconnection is next to the triple bond. 

Following these findings, Gleiter and co-workers reported that in a series of S-alkyl-substituted alkynes, the regiochemical outcome of the reaction... 

On the other hand, the cyclization reaction of a vinyllithium onto an acetylenic unit provides an efficient route to five- and six-membered bis-exocyclic 1,3-dienes, which react stereoselectively with a wide range of dienophiles157. The 5-exo carbolithiation reaction of vinyllithiums 369, derived from the corresponding vinyl bromides, is syw-stereospecific giving, after hydrolysis, the /(-isomer of five-membered outer-ring dienes 370 and tolerates aryl-, silyl- or alkyl-substituents at the distal acetylenic carbon (Scheme 97). However, the alkyl-substituted alkynes are far more resistant to rearrangement than the aryl- or silyl-substrates and the addition of TMEDA and longer reaction times are needed for the latter... 

Regardless of the mechanism, three clear generalizations concerning the reactions can be made. First, in cycloadditions to monosubstituted (alkyl/ aryl) alkynes only the 5-substituted isoxazole is obtained. Only in the case of perfluoroalkylalkynes has any significant amount of the 4-substituted isomer (31) been observed.89 Second, the reaction is hindered by bulky substituents on the alkyne. Finally, the reaction is not appreciably hindered by bulky substituents on the nitrile oxide, even when they are so large as to inhibit dimerization almost completely.59 Competition for phenylethyne between pentachloro- and pentabromobenzonitrile oxide gave approximately equimolar amounts of the two adducts (32)90... 

The cis double bond can be formed by hydrogenation of an alkyne, which can be synthesized by an alkylation reaction of a terminal alkyne. 

The RCM is also efficient in the case of enynes of type 144 and 145, obtained from iV-BOC-hydroxylamine, which underwent a sequence of two alkylation reactions. The enyne 144 was obtained if the bromoalkyne is initially employed and then the bromoalkene. Enyne 145 was obtained when the first alkylation was carried out with bromoalkene and the second with bromoalkyne. Both enynes 144 and 145 cyclized in the presence of Grubbs catalyst to give the oxazocines 122 and 121, respectively, in good yields, although it was necessary to conduct the reaction under high-dilution conditions (0.007 M). It was observed that when the alkyne moiety is bound to the oxygen the cyclization is faster with increased yields (Scheme 30) <2003SL2017>. 

Terminal alkynes are weakly acidic. The alkyne hydrogen can he removed by s strong base 9uch ae Na NH.. to yield nn a<%tylide anipn An acetylide anion ads as a nucleophile and can displace a halide ion from a primary alkyl halide in a n alkylation reaction. Acetylide anions are more stable iJian either alkyl anions or vinylic anions because their m ative charge is in a hybrid orbital with 50% s character, allowing the charge to be doser to the nucleus. 

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