Addition reactions to alkynes

In one case, the addition reaction was neither regiospecific nor stereospecific124 (equation 90). Obviously, one will have to choose the reaction conditions for the addition reactions to alkynes carefully when stereochemistry is important. 

Complex 3c, a catalytic precursor for addition reactions to alkynes (65), reacts at room temperature with a variety of terminal alkynes in alcohols to produce stable alkoxyl alkyl carbene ruthenium(II) derivatives 109 in good yields (Scheme 7). Reaction of 3c (L = PMe3), with trimethylsilyacetylene in methanol gives the carbene ruthenium complex 110, by protonolysis of the C—Si bond, whereas with 4-hydroxy-l-butyne in methanol the cyclic carbene complex 111 is obtained (65,66). 

This chapter will describe various additions to alkynes as a way to generate functional intermediates. In the first section, general additions of O, N, and P nucleophiles will be presented. Ruthenium-catalyzed hydrosilylation of alkynes will be described as an addition reaction to alkynes followed by ruthenium-catalyzed addition of C nucleophiles. 

The related addition reaction to alkynes produces cyclopropenes, and it has also been developed with copper-based Tp CuL catalysts. Both terminal and internal alkynes were converted into these three-membered rings in good yields with activities at least comparable with those of the well-known Rh2(OOCR) catalysts (Scheme 9b). 

Heteronuclear addition reactions to alkynes usually produce the corresponding trans-alkene derivatives. However, in the case of strained cyclic alkynes, these would be even more heavily strained than the starting alkyne. Thus, in most reactions, cis-products are observed. The initial addition of the electrophile may, however, still proceed in an anh -manner, as was shown by Krebs et al. [1 b] for the reaction of a cycloheptyne derivative with trichloromethylsulfenyl chloride (Scheme 8-21). This reaction produced the first seven-membered rm s-cycloalkene derivative to be isolable at room temperature. 

It should be noted that formation of trans-product can be achieved in an anti-addition reaction through the outer-sphere mechanism. Theoretical studies have demonstrated that syn-addition and anti-addition reactions may start from the same 7i-complex, and direction of the multiple bond activation depends on the polarity of solvent [17, 18]. Relative reactivity in the inner-sphere and outer-sphere mechanisms contributes to the overall -/Z- selectivity of the addition reaction to alkynes (stereoselectivity issue). In some cases it is possible to switch the direction of C-Het bond formation by finding a suitable ligand [19]. In case of alkenes syn-addition and a f -addition processes do not necessarily result in different stereochemistry (unrestricted rotation around the single C-C bond in the product). Occurrence of these mechanisms for the N [20, 21], P [22, 23], O [24-26], S, Se [27, 28] heteroatom groups and application of different metal catalysts are discussed in detail in the other chapters of this book. Stereochemical pathways of nucleometallation and development of enantioselective catalytic procedures were reviewed [29]. In this chapter we focus our attention on the mechanism of irmer-sphere insertion reaction involving double and triple carbon-carbon bonds. 

Scheme 8.1 Possible products in a P-H bond addition reaction to alkynes...

The initial addition products to alkynes are not always stable. Addition of acetic acid, for example, results in the formation of enol acetates, which are converted to the corresponding ketone under the reaction conditions.151... 

Some of the most synthetically useful addition reactions of alkynes are with organometallic reagents, and these reactions, which can lead to carbon-carbon bond formation, are discussed in Chapter 8. 

A review which covered the different known methods for the preparation of chiral amines and analysis of the different chiral catalysts used, correlating them according to their efficiency, selectivity, and flexibility, has been presented.279 Reduction reactions of alkenes, arenes, alkynes and allenes resulting in the formation of two or more C-H bonds280 and reduction and addition reactions of alkynes to alkenes to form one or more C=C bonds281 have been reviewed. 

The new reactivity mode for the in-situ generation of metal alkynylides was exploited in addition reactions to aldehydes. Stoichiometric quantities of Zn(OTf)2 and NEt3 or Hiinig s base effected deprotonation of a number of alkynes which underwent smooth addition to various aldehydes to furnish the corresponding propargylic alcohols (Eq. 5) [13]. Subsequent studies revealed that apart from Zn(OTf)2 other zinc sources such as ZnCl2 and ZnC03 could be used in this reaction (Eq. 6) [14]. 

Angle strained cycloalkynes exhibit enhanced reactivity, particularly in addition reactions to the triple bond, over analogous open chain alkynes. Therefore many reactions can be carried out with angle strained cycloalkynes which are not feasible or at least cannot be carried out under such mild conditions with analogous open chain alkynes. This review concentrates on the reactions typical for angle strained cycloalkynes, while those typical also for normal alkynes are not discussed in detail. 

However, their intermolecular addition reactions with alkynes are mostly aimed at synthesizing substituted aLkenes, ° and only very few cascade reactions that are initiated by P radical addition to C = C triple bonds have been reported. Renaud and coworkers developed a simple one-pot procedure for the cyclization of terminal alkynes mediated by dialkyl phosphites (Scheme 2.35). In this radical chain procedure, dialkyl phosphite radicals, (R0)2P =0, undergo addition to the C = C triple bond in 190, which triggers a radical translocation (l,5-HAT)/5-eAO cyclization cascade. The sequence is terminated by hydrogen transfer from dialkyl phosphite to the intermediate 194 and regeneration of P-centered radicals. 

As indicated in Scheme 39, the initial process is the formation of the a-phenylseleno derivative 249 tvhich gives a second addition reaction to afford products 245, identical to those formed from terminal alkynes. This reaction seems to be of general application since alkyl, vinyl, and aryl methyl ketones give the a-ketoacetals of the type 250,251 and 252 with excellent results in every case. 

In the remainder of Chapter 12, the oxidation of alkenes, alkynes, and alcohols— three functional groups already introduced in this text—is presented (Figure 12.8). Addition reactions to alkenes and alkynes that increase the number of C—O bonds are described in Sections 12.8-12.11. Oxidation of alcohols to carbonyl compounds appears in Sections 12.12-12.14. 

Nickel(O) complexes undergo oxidative addition reactions with alkynes to give nickelacyclopentadienes and also react under certain conditions with carbon dioxide or isocyanates to form oxanickelacyclopentenones (87) " or azanickelacyclopentenones (88) (Scheme 30). In both cases the chelating basic ligand TMEDA (tetramethylethylenediamine) influences the reaction strongly. 

The most important lr(I) complexes are rra/ 5-IrCl(CO)(PPh3)2 (Vaska s complex) and its phosphine derivatives, since they provide clear examples of oxidative addition reactions. Scheme 11.5 summarizes the addition reactions to IrCl(CO)(PPh3)2 [72]. Alkyl halides, acyl halides. H.. and SnCl4 oxidatively add to the Ir center, and reactions with O2. alkyne. CO. and SO2 give their coordinated complexes without complete cleavage of the appropriate bond. 

Linear Addition Reactions to C = C Bonds 2.1.1.5.1. Radical Addition of Perhaloalkanes to Various Alkynes Simple Alkynes... 

Other activated systems, specifically activated alkynes and hydrazones, have been employed as radical acceptors for alkyl radicals generated from alkyl halides and Sml2 [11]. Radical addition reactions to activated alkynes appear to be more capricious than the reactions with activated alkenes, and thus are perhaps more limited in scope. Additionally, mixtures of diastereomers inevitably result from such systems (Eq. 11) [12]. Diphenylhydrazones were shown to react approximately 200 times faster than the analogous alkenes in 5-exo additions as determined in a series of studies by Fallis and Sturino [13]. Reasonable diastereoselectivities were exhibited in these processes (Eq. 12). 

Thus alkynes, like alkenes, undergo electrophilic addition reactions. We will see that the same electrophilic reagents that add to alkenes also add to alkynes and that— again like alkenes—electrophilic addition to a terminal alkyne is regioselective When an electrophile adds to a terminal alkyne, it adds to the sp carbon that is bonded to the hydrogen. The addition reactions of alkynes, however, have a feature that alkenes do not have Because the product of the addition of an electrophilic reagent to an alkyne is an alkene, a second electrophilic addition reaction can occur. 

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