Other Additions to Alkynes

Organometallic complexes of the /-elements have been reported that will perform both intra-and intermolecular hydroamination reactions of alkenes and alkynes, although these lie outside of the scope of this review.149-155 Early transition metal catalysts are not very common, although a number of organometallic systems exist.156-158 In these and other cases, the intermediacy of a metal imido complex LnM=NR was proposed.159,160 Such a species has recently been isolated (53) and used as a direct catalyst precursor for N-H addition to alkynes and allenes (Scheme 35).161,162... 

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],... 

A Ag/Pd-cathode hydrogenates 2-butyne-1,4-diol and acetylene dicarboxylic acid exclusively to the cis-olefin [323]. Similar results were obtained at a Cu net covered with spongy silver [324]. With dimethyl butynedioate the cis/trans ratio of the product dimethyl butenedioate on a Pd black cathode decreased with increasing pH both in electrolytic and catalytic hydrogenation [325]. On the other side at a Hg cathode a trans addition to alkynes occurs [326]. In methy-lamine/liCl, dialkylacetylenes are reduced to trans-olefins. Nonconjugated aromatic internal acetylenes are selectively reduced to aromatic trans-olefins [327]. 

As expected, additions to alkynes are also subject to control by polar functions nearby. Thus, nucleophilic attack on trifluoromethylacetylene [116], cyanoacetylene [137], and ethylthioacetylene [138] occurs at the terminal jp-hybridized carbon atom, the substituent at the other end of the triple being an acceptor in all cases. This behavior is to be contrasted with the mode of addition on ethoxyacetylene [3 39], aminoacetylenes [120], The vinylogue, 4-dimethyl-aminobut-3-en-l-yne [121], reacts with aniline at the internal position of the akyne linkage. However, a 2 1 regiose-lectivity, favoring the methanol adduct predicted by the polarity alternation rule, has been observed for the addition of jV,jV-bis(trifluoromethyl)ethynylamine [122], It is not known whether steric factors play a role in the decreased regioselectivity. 

Dicyclopentadienyltitanium dichloride is possibly superior to titanium tetrachloride as a catalyst. Nickel(ll) compounds are also active, but with these catalysts concurrent addition of the organomagnesium compounds to carbon-carbon multiple bonds (see Section 4.1) causes complications. Examples of hydromagnesiation by Grignard reagents are listed in Table 3.8. As will be seen from entries in Table 3.8, the stereochemistry of addition to alkynes is syn. The regiochemistry is also usually predictable in the relevant examples in Table 3.8, one regioisomer is obtained mainly or exclusively. In other cases, however, mixtures are formed [54]. 

Several other lines of evidence support the IIT mechanism. First, the carbanion (alkenide) intermediate is real—it turns up in other reactions. Without it how would one rationalize most of the standard anti additions to alkynes exemplified by equation (1) Then, base-induced deprotonations of alkenes, which have been demonstrated by proton labelling, lead directly to this anion > . In Scheme 3 (see Section II.B) we showed how addition (equation 1), substitution (equation 2) and elimination may be mechanistically interrelated by this anion. Later we shall show that for certain systems, product distributions, element effects and Hammett p-values are in accord with the IIT pathway. 

Moving the other way to Group VA, the system depicted in equation (2) presents opportunities for highly regioselective additions to alkynes, although subsequent reactions may be complex (equation 56). This, coupled with the difficulty of effecting hydrometallation, makes it unlikely that such systems will find much use in synthesis. 

Thus, the reaction of 144 with alkynes yielded polymer-bound intermediates 145. The release of the final products was performed in two steps. After cleavage of the Boc group under acidic conditions, the products 146 were cleaved from the support under basic conditions. In addition to alkynes, other dienophiles such as enol ethers could also be employed. 

This ring is formed by reaction of a 3-amino-5-chloroindole-2-carboxylic acid with DEAD (review of addition to alkynes [2816]) in alkaline solution when the chlorine atom was replaced by other substituents, a mixture of products was obtained. 

Similar reaction sequences have been used in the synthesis of the vitamin D system103-108 and other polycyclic ring systems109 -113. Instead of carbanion capture of an alkyne-carbapalladation adduct, a subsequent insertion of an unsaturated unit also leads to dicarborative addition to alkynes. If used in intramolecular versions, polycyclic products are obtained61-63,114. In some cases more complicated cyclopropane formations are involved in these conversions if further insertions can lake place before dehydropalladation occurs45 64. 

Fahey and Lee (reference 283) found the addition of HCl to 3-hexyne in acetic acid to be termolecular, first order in the alkyne and second order in HCl. The reaction showed primarily anti addition at 25°C, although there was more syn addition at higher temperatures. Similar considerations apply in the addition of other electrophiles to alkynes (reference 275). 

In recent years, much attention has been paid on the Baylis-Hillman reaction for construction of C-C bond between an aldehyde and an activated alkene or alkyne [248]. The major drawbacks of the Baylis-Hillman reaction are its slow reaction rate and limited range of substrates. To overcome these shortcomings, many efforts have been made, such as using Lewis acids or various other additives to activate carbonyl electrophiles [249]. The use of TiCU to mediate Baylis-Hillman reaction represents a commonly applied approach to enhance the reactivity. This part of work has been well documented in a recent comprehensive review [248d]. 

Several new syntheses of vinylsilanes have been described. Tris(trimethyl-silyl)aluminium undergoes 5yn-addition to alkynes alternatively the same -isomers can be obtained by photochemical isomerisation of Z-1-alkenyl-silanes. Other methods described involve treatment of the lithium salts of hydrazones with trimethylsilyl chloride, Wurtz-type coupling with vinyl bromides, and reaction of acetylenes with a silyl-copper reagent followed by an electrophile. Using the hydrazone method, a route has been devised for 1,2-carbonyl transposition within ketones (Scheme 17). ... 

The other studies of thiol addition to alkynes in the recent literature involve the ionic mechanism, the major interest being the stereoisomer ratios of the resulting vinyl sulphides. -An interesting study of the addition of 2 equivalents of PhCHaSH to acetylenedicarboxylic acid in alkaline solution includes an assessment of factors allowing control of the proportions of the resulting racemic and me.ro-l,2-bis(benzylthio)succinic acids. 

Several Pd(0) complexes are effective catalysts of a variety of reactions, and these catalytic reactions are particularly useful because they are catalytic without adding other oxidants and proceed with catalytic amounts of expensive Pd compounds. These reactions are treated in this chapter. Among many substrates used for the catalytic reactions, organic halides and allylic esters are two of the most widely used, and they undergo facile oxidative additions to Pd(0) to form complexes which have o-Pd—C bonds. These intermediate complexes undergo several different transformations. Regeneration of Pd(0) species in the final step makes the reaction catalytic. These reactions of organic halides except allylic halides are treated in Section 1 and the reactions of various allylic compounds are surveyed in Section 2. Catalytic reactions of dienes, alkynes. and alkenes are treated in other sections. These reactions offer unique methods for carbon-carbon bond formation, which are impossible by other means. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

We have already discussed one important chemical property of alkynes the acidity of acetylene and terminal alkynes In the remaining sections of this chapter several other reactions of alkynes will be explored Most of them will be similar to reactions of alkenes Like alkenes alkynes undergo addition reactions We 11 begin with a reaction familiar to us from our study of alkenes namely catalytic hydrogenation... 

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