Nucleophilic addition to alkynes

In 1979, Claesson et al. observed the formation of the dihydropyrrole 125 and the pyrrole 126 when trying to purify the amine 124 by GLC [85]. They suspected that an initial cycloisomerization first leads to 125 and a subsequent dehydrogenation then delivers 126. Guided by other intramolecular nucleophilic additions to alkynes that are catalyzed by AgBF4, they discovered that this catalyst efficiently allowed the transformation of 124 to 125 (Scheme 15.38). Reissig et al. found that with enantio-merically pure substrates of that kind a cyclization without racemization is possible with Ag(I) catalysts [86],... 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

The addition of stabilized nucleophiles—both carbon and heteronucleophiles—to activated alkynes has been used far less often in organic synthesis than the corresponding addition to activated alkenes. Since several excellent reviews on nucleophilic additions to alkynes appeared in the 1960s and 1970s,10 this section includes only a few representative examples from the early literature and some more recent applications. 

These results rationalize, in MO terms, the greater reactivity of alkynes than al-kenes toward nucleophiles, and the trans-stereoselectivity of nucleophilic additions to alkynes. It is now clear why alkynes behave as if the LUMO energies of these molecules were lower than those of the corresponding alkenes the effective EAs of alkynes are higher than those of alkenes. There are further consequences. 

Nucleophilic Additions to Alkynes and Reactions via Vinylidene Intermediates... 

Here, we shall focus on ruthenium-catalyzed nucleophilic additions to alkynes. These additions have the potential to give a direct access to unsaturated functional molecules - the key intermediates for fine chemicals and also the monomers for polymer synthesis and molecular multifunctional materials. Ruthenium-catalyzed nucleophilic additions to alkynes are possible via three different basic activation pathways (Scheme 8.1). For some time, Lewis acid activation type (i), leading to Mar-kovnikov addition, was the main possible addition until the first anfi-Markovnikov catalytic addition was pointed out for the first time in 1986 [6, 7]. This regioselectiv-ity was then explained by the formation of a ruthenium vinylidene species with an electron-deficient Ru=C carbon site (ii). Although currently this methodology is the most often employed, nucleophilic additions involving ruthenium allenylidene species also take place (iii). These complexes allow multiple synthetic possibilities as their cumulenic backbone offers two electrophilic sites (hi). 

The Kiev group is still one of the few providing kinetic data on nucleophilic addition to alkynes - Their general rate law (equation 101) is adaptable to... 

Product orientation alone is insufficient for elucidation of the mechanisms of these addition reactions as the same products would be obtained by either electrophilic or nucleophilic addition. It is well knowTi that the greater electronegativity of the sp carbon in alkynes leads to lower reactivity with electrophiles and greater reactivity with nucleophiles compared with the sp carbon of alkenes. A number of nucleophilic additions to alkynes such as addition of alcohols and weak acids are known ° . 

Problems 9.38-9.42 emphasize mechanistic reasoning. By thinking mechanistically you reduce the need to memorize facts while increasing your ability to analyze and understand new material. Nucleophilic addition to alkynes, for example, is not covered in this chapter but is the focus of problem 9.42, which can be solved by thinking mechanistically. 

For discussions of nucleophilic addition to alkynes, see Miller, S. I. Tanaka, R. in Thyagarajan, B. S., Ed. Selective Organic Transjbrmations, Vol. I Wiley-Intersdence New York, 1970 pp. 143-238 Dickstein, J. L Miller, S. I. in Patai, S., Ed. The Chemistry of the Carbon-Carbon Triple Bond, Part 2 Wiley-Interscience Chichester, England, 1978 pp. 843-911. 

As we will see in later chapters, anionic and metal-catalyzed nucleophilic additions to alkynes are an important ronte to indoles. One of the first such examples is that of Johnson and Subramanian, who found that meM-anisidine... 

Nucleophilic addition to alkyne complexes gives vinylmetal species. A particularly interesting variant of this reaction is addition to an 18e complex containing a 4e alkyne (see Section 5.1). If the product were a tj -vinyl, then the complex would be 16e, and so a 3e tt -vinyl is usually found ... 

M. Pempointner, A. S. K. Hashmi. Fully Relativistic, Comparative Investigation of Gold and Platinum AUcyne Complexes of Relevance for the Catalysis of Nucleophilic Additions to Alkynes. /. Chem. Theory Comput., 5 (2009) 2717-2725. 

Nucleophilic addition to alkynes is promoted by a number of metal catalysts. One of the simplest catalysts is silver nitrate, which can be more effective when absorbed onto silica gel. ° Treatment of alkynyl alcohols 6.190 with this reagent is a useful route to furans, as the cxo-cyclic double bond, under the reaction conditions, migrates to the endo-cyclic position (Scheme 6.74). 

Nucleophilic addition to alkyne complexes gives vinylmetal species. A particularly interesting variant of this reaction is addition to an 18e complex containing... 

Gold-catalyzed nucleophilic addition to alkynes are operationally safe and simple to perform, and do not generally require rigorously inert reaction conditions. 

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