Addition of Nucleophiles to Alkyne

The addition of O- and A-nucleophiles to alkynes catalysed by a phosphazene base, Bu-P4 base was investigated. Alkynes were easily transformed to enol ethers and enamines in dimethyl sulfoxide (DMSO) by the addition of nucleophiles. When phenylacetylene was 

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The transition metal-catalyzed addition of nucleophiles to alkynes is a broad field that has been studied extensively... 

Phosphines are known to impart bielectrophilic character to electron deficient alkynes such as 58 and promote y-addition of nucleophiles to alkynes. Binucleophiles such as thioamides could potentially give two thiazoline isomers 59 and 60. It is proposed that an initial vinyl phosphonium intermediate is formed which prefers to react with hard nucleophiles such as nitrogen rather than sulfur consequently, only thiazole 59 was observed. 

The calculations also suggest why tram addition of nucleophiles to alkynes is invariably observed, and why the apparently unusual trajectories proposed by Baldwin48 for such attacks occur. Table 3 shows the energy changes which occur upon various distortions of acetylene and ethylene, as well as energies of interaction of the various geometries of these species with hydride ion, a model nucleophile. 

Catalytic addition of nucleophiles to alkyne and allene derivatives using the Lewis acid and triphenylphosphine gold(I)trifluoroacetate are described (2). 

Palladium salts also promote the addition of nucleophiles to alkenes and alkynes. The Pd-catalyzed additions of nucleophiles to alkynes, which is useful for intramolecular cyclizations such as the isomerization of 2-alkynylphenols to benzofurans, proceeds by exactly the same mechanism as does the Hg-catalyzed reaction. However, the Pd-catalyzed additions of nucleophiles to alkenes takes the course of substitution rather than addition because alkylpalladium complexes are unstable toward /3-hydride elimination. The Pd-catalyzed nucleophilic substitutions of alkenes are discussed later in this chapter (Section 6.3.6). 

The addition of nucleophiles to alkynes is catalyzed by both Hg(II) and Pd(II) salts. The intermediate alkenylmetal(II) complex is stable to /3-hydride elimination, but the C-metal bond can be replaced by a C-H bond by a protonation-fragmentation mechanism. 

Pd(Il) salts catalyze the addition of nucleophiles to alkynes by exactly the same mechanism. The reaction is useful for intramolecular cyclization, such as the isomerization of 2-alkynylphenols to benzofurans. 

Scheme 31 depicts an example of the antz-Markovnikov addition of nucleophiles to alkynes. (Ty -Cymene)RuCl2(PMe3) complex 111 mediated the reaction between diethylamine 112, CO2, and phenylacetylene 113 to provide a mixture of trans- and cz5-carbamates 114 and 115 respectively in the ratio of 5 1 [53]. 

Vinyl complexes are typically prepared by the same methods used to prepare aryl complexes. Vinyl mercury compounds, like aryl mercury compoimds, are easily prepared (by the mercuration of acetylenes), and are therefore useful for the preparation of vinyl transition metal complexes by transmetallation. The use of vinyl lithium reagents has permitted the s rnthesis of homoleptic vinyl complexes by transmetallation (Equation 3.35). Reactive low-valent transition metal complexes also form vinyl complexes by the oxidative addition of vinyl halides with retention of stereochemistry about the double bond (Equation 3.36). Vinyl complexes have also been formed by the insertion of alkynes into transition metal hydride bonds (Equation 3.37), by sequential electrophilic and nucleophilic addition to alkynyl ligands (Equation 3.38), and by the addition of nucleophiles to alkyne complexes (Equation 3.39). The insertion of alkynes into transition metal alkyl complexes is presented in Chapter 9 and, when rearrangements are slower than insertion, occurs by s)m addition. In contrast, nucleophilic attack on coordinated alkynes, presented in Chapter 11, generates products from anti addition. 

In most cases, the addition of nucleophiles to alkynes involves as the first step the electrophilic activation of the triple bond. With many Lewis acid metals, this process leads to Markovnikov addition (Scheme 5a). With metals able to facilitate... 

In fact, a mechanism for this reaction can be drawn that does not involve Pd at all, but let s assume that Pd is required for it to proceed. Cl- must be nucleophilic. It can add to Cl of the alkyne if the alkyne is activated by coordination to Pd(II). (Compare Hg-catalyzed addition of water to alkynes.) Addition of Cl- to an alkyne-Pd(II) complex gives a o-bound Pd(II) complex. Coordination and insertion of acrolein into the C2-Pd bond gives a new a-bound Pd(II) complex. In the Heck reaction, this complex would undergo P-hydride elimination, but in this case the Pd enolate simply is protonated to give the enol of the saturated aldehyde. 

In chronological order, the next milestones in research were the studies by Fukuda and Utimoto on the addition of nucleophiles (water, alcohols and amines) to alkynes [13]. A decade later, Teles obtained notable turnover numbers (TONs) and turnover frequencies (TOFs) in the addition of alcohols to alkynes [14]. 

Until 1998, only gold(III) was believed to be effective for catalyzing these processes because, as mentioned previously, only the gold(I) compound K[Au (CN)2] was tested and it was inert to catalysis. Fortunately, Teles et al. reported very strong activity in the addition of alcohols to alkynes when they used cationic gold( I) -phosphane complexes [14]. In this study, the aforementioned authors tested for the first time the suitability of nucleophilic carbenes that displayed even greater activity than other gold complexes, but they were unable to synthesize the subsequent cationic derivatives. 

The formation of metal vinylidene complexes directly from terminal alkynes is an elegant way to perform anti-Markovnikov addition of nucleophiles to triple bonds [1, 2], The electrophilic a-carbon of ruthenium vinylidene complexes reacts with nucleophiles to form ruthenium alkenyl species, which liberate this organic fragment on protonolysis (Scheme 1). 

Following the orbital requirement, anti additions of the type (144) might (naively) be expected to follow third-order kinetics. It turns out that this is not general, nor is it a sufficient or necessary condition for anti SS. Over the past fifteen years, Shilov s group has found interesting cases of nucleophilic participation in the addition of acids to alkynes and alkenes (Dvorko and Shilov, 1964 Dvorko and Mironova, 1965), e.g. 

The C-C bond formation can also be obtained via a first-step addition of a heteroatom to alkynes. Thus, the reaction of the three components terminal alkyne, water and enone led to 1,5-diketone with atom economy, using the system CpRuCl(COD)/NH4PF6 and In(0S02CF3)3 as a cocatalyst [58,59] (Eq. 43). The mechanism is postulated to proceed by the ruthenium-catalyzed nucleophilic addition of water to alkynes to generate a ruthenium enolate intermediate allowing further insertion of enone and formation of 1,5-diketones after protonation. 

Davidson has utilized electron-withdrawing alkyne substituents to promote addition of nucleophiles to neutral cyclopentadienyl alkyne derivatives. With bisalkyne reagents the conversion of one hexafluorobutyne to an rj2-vinyl ligand provides four electrons and limits the remaining alkyne to a formal two-electron donor role. The CF3 substituents are important in both increasing the electrophilicity of the alkyne carbon and in stabilizing the N = 2 role for the intact alkyne retained in the product [Eq. (53)]. 

Prior to this report, the addition of bromine to alkynes in acetic acid was suggested to occur via an electrophilic process (although not explicitly involving vinyl cations as intermediates) by Robertson et al. (1950). The reaction rate was found to obey mixed second and third-order kinetics and to be enhanced by electron-supplying substituents. It was also noted that strong electron-withdrawing residues bonded to the triple bond may switch the reaction pattern towards a nucleophilic... 

It is evident from the above arguments that the addition of halogens to alkynes may occur by a multiplicity of mechanisms. One more argument is offered by a kinetic study of the addition of bromine to diphenylacetylene in bromobenzene reported by Sinn et al. (1965). In this case kinetic data are better interpreted on the basis of a nucleophilic mechanism involving the intermediacy of a vinyl anion, rather than an electrophilic reaction. 

Many asymmetric C-C bond formation processes are based upon the addition of nucleophiles to the prochiral faces of double bonds to create the chiral carbon center. Since the oxidative alkynylation is believed to occur through the addition of the terminal alkyne to an in situ generated iminium ion, Li and co-workers examined the potential for the development of an asymmetric variant to the oxidative alkynylation process (Scheme 16) [33, 34],... 

The nucleophilic addition of alcohols to alkynes was reported by Utimoto with NaAuCU and later by Teles with cationic gold complexes.The enol ethers formed can be hydrolyzed to form carbonyl compounds or trapped as ketals (equations 4 and 5). An intramolecular version of this reaction was reported by the group of Genet to give bicyclic ketals (equation On the basis of this concept, a glycosidation... 

Carboxylic acids,carbonates, carbamates, sulfoxides, and related nucleophiles also add to alkynes (equations 19-22). Similarly, the intramolecular addition of amides to alkynes leads to oxazoles by isomerization of the initially formed 5-methylene-4,5-... 

This rarer, and rather surprising, approach to Z alkenes can give excellent results, particularly in the addition of nucleophiles to butadlyne. The base-catalysed addition of methanol gives an excellent yield of Z-l-methoxybut-l-en-3-yne. This reaction is so easy to do that the product is available commercially. Notice that methanol adds once only you would not expect nucleophiles to add to a simple alkyne and it is the conjugation that makes addition possible. 

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