Activation of the Alkyne

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

The postulated mechanism for the reaction involves activation of the alkyne by jt-coordination to the cationic (IPr)Au% followed by direct nucleophilic attack by the electron-rich aromatic ring to form product 111. Alternatively, two 1,2-acetate migrations give the activated aUene complex, which can be cyclised to product 110 by nucleophilic attack of the aromatic ring on the activated aUene (Scheme 2.21) [92]. 

Scheme 4-14 Catalytic cycle for the IH of aminoalkynes via activation of the alkyne...

Catalytic quantities of transition- or non-transition metals promote the cyclization of 2-alkynynylbiphenyl analogs to phenanthrene or fulvene analogs. The mechanism is thought to involve activation of the alkyne by metal coordination, prior to cyclization (Equations (179) and (180)).146... 

Potassium tert-butoxide reacts with copper iodide to generate a copper / -butoxide species 98 (Scheme 29). Activation of the alkyne 94 by this copper catalyst (intermediate 96) allows the enolate attack to afford the cyclic... 

The skeletal rearrangements are cycloisomerization processes which involve carbon-carbon bond cleavage. These reactions have witnessed a tremendous development in the last decade, and this chemistry has been recently reviewed.283 This section will be devoted to 7T-Lewis acid-catalyzed processes and will not deal, for instance, with genuine enyne metathesis processes involving carbene complex-catalyzed processes pioneered by Katz284 and intensely used nowadays with Ru-based catalysts.285 By the catalysis of 7r-Lewis acids, all these reactions generally start with a metal-promoted electrophilic activation of the alkyne moiety, a process well known for organoplatinum... 

Extensions of the electrophilic activation of the alkyne moiety as well as an alkene moiety have been developed and applied. The applications include various reactions, for instance, Friedel-Crafts type alkylations,323 anchimeric assistance of heteroatomic moiety generally followed by rearrangements (see below), implementation of more sophisticated functional groups such as ynamides and allenynes, which are discussed below. 

Gycloisomerization of a disubstituted alkyne sometimes required activation of the alkyne by the addition of a conjugated carbonyl and performing the reaction at a higher temperature as in Equation (38). The geometry of the alkene determines the regioselectivity of the /3-hydride elimination, as ( )-60 gave predominantly 61 (Equation (38)), while 62 was the major product of the cycloisomerization of (Z)-60 (Equation (39)). 

In Section 6.3.6, it was emphasized that C02 and secondary amines could add to terminal alkynes in the presence of ruthenium catalysts to afford carbamates. Under comparable conditions (393-413 K, 5 MPa Ru-catalysts), primary amines will afford symmetrical disubstituted ureas in moderate yield [131]. It is worth noting that although the final urea does not contain the starting alkyne, its catalytic formation requires, besides the Ru-catalyst, the presence of a stoichiometric amount of a 1-alkyne (e.g., a propargylic alcohol). A possible mechanism (Scheme 6.32) for this catalytic reaction may involve activation of the alkyne at the metal center, a nucleophilic addition of the carbamate to the activated alkyne to produce... 

The first example involves the dimerization of terminal alkynes. It takes place via initial activation of the alkyne C-H bond, but several examples involve a vinylidene intermediate. In most cases, conjugated enynes are obtained by ruthenium-catalyzed tail-to-tail dimerization [84,85], as in the following example [85] (Eq. 63). 

Alkynes can also be used as radical acceptors for the generation of cyclo-pentanols bearing an exocyclic alkene, but in nearly all cases the yields are modest compared with those obtained in the related cyclisations of alkenes. Activation of the alkynes by electron-withdrawing groups or silyl substituents leads to more efficient 5-exo-dig ring closure.55... 

Pd-catalyzed cycloisomerization of (Z)-2-en-4-yne-l-thiols 111 gives substituted thiophenes 112. The mechanism involves electrophilic activation of the alkyne moiety by Pd(ll) followed by intramolecular cyclization, protonolysis, and aromatization (Scheme 25) <20000L351>. S-Endo cyclization of alkynyl thiols 113 using a Mo, W, or Cr catalyst affords dihydrothiophene 114 <2000S970>. 

Synthesis of chiral allylic amines from alkynes and A -sulfonylaldimines involves reductive activation of the alkynes. The metal atom of iridacyclopropene intermediates also gathers the sulfonylimine as a bidentate ligand prior to bonding reorganization within the coordination sphere. The absolute stereochemical sense is governed by the chiral ligand employed (such as a member of the BIPHEP series). 

Abstract Bimetallic catalysts are capable of activating alkynes to undergo a diverse array of reactions. The unique electronic structure of alkynes enables them to coordinate to two metals in a variety of different arrangements. A number of well-characterised bimetallic complexes have been discovered that utilise the versatile coordination modes of alkynes to enhance the rate of a bimetallic catalysed process. Yet, for many other bimetallic catalyst systems, which have achieved incredible improvements to a reactions rate and selectivity, the mechanism of alkyne activation remains unknown. This chapter summarises the many different approaches that bimetallic catalysts may be utilised to achieve cooperative activation of the alkyne triple bond. 

This review is not intended to be fully comprehensive but instead should serve to highlight current understanding of bimetallic cooperative catalysis as it applies to the activation of the alkyne triple bond. We have divided the review into four sections, separated by reaction type, which emphasise different aspects of the bimetallic alkyne activation mechanism. These four sections are as follows ... 

Schreiber and Luo exploited domino sequences in both the coupling and pairing phases [25]. A gold-catalyzed cyclization of alkyne 157 was employed to obtain molecules that could subsequently be used in the pairing reaction. Activation of the alkyne by a gold(I) complex yielded the cydized cationic species 160,... 

Starting from tetrahydrocyclopenta[f)]furan-2-one 342, enyne 343, the substrate for the domino reaction, was prepared in 12 steps and with an overall yield of 45%. Exposure of 343 to the electron-rich gold(I) complex (t-Bu)2P(o-biphenyl)AuCl at room temperature afforded cis-hydrindanone 344 in 78% yield as a single stereoisomer (Scheme 14.54). The postulated mechanism involved Au(I) activation of the alkyne to initiate the cationic olefin cyclization of 346 to give carbocation 347, which then underwent a pinacol rearrangement to the final product 344. An originally attempted Lewis acid-catalyzed domino Prins/pinacol rearrangement of... 

Dixneuf et al. first reported that various 2,3,5-trisubstituted furans 114 could be synthesized via a cycloisomerization of (Z)-pent-2-en-4-yn-l-ols 113 in the presence of Ru(II)-catalyst (Scheme 8.45) [162-164]. The corresponding furans were obtained generally in good to high yields, though this reaction was specific to terminal alkynes only. The authors proposed a mechanism based on the electrophilic activation of the alkyne moiety followed by intramolecular addition of the hydroxy function at the internal carbon atom of alkyne. A subsequent protiodemetalation-isomerization sequence furnished the furan 114 (Scheme 8.46). 

The gold(I)-catalyzed intramolecular Schmidt reaction of azido alkynes 49 provides easy entry to a series of pyrroles 54 with a variety of substitution patterns. The proposed mechanism involves gold(I)-induced activation of the alkyne toward addition by the proximal nitrogen of the azide. Subsequent loss of nitrogen leads to cationic intermediate 52, which is... 

A related example is also worth noting and involves the reaction of aryl iodides or vinyl triflates with 13 nnder carbonylative conditions to give 14 (43-83% yields) along with small amonnts of 15 (Scheme 24)P This reaction can in principle proceed by either acylpalladation or electrophilic activation of the alkyne moiety. Based on the mechanistic investigation of the noncarbonylative reaction, the electrophilic activation pathway seems to be the most likely mechanism. It is, however, interesting to see that small changes in the substrate can completely change the course of the reaction. 

Gagosz et al. reported Au(l) catalyst 147-catalyzed alkylation of alkynyl ethers which produced cyclohexane 146 as major product (Scheme 54) [127]. Theoretically, the electrophilic activation of the alkyne 145 by Au(l) initiates a [1,5]-hydride shift to furnish oxocarbenium ion 1, interaction of which with the pendant nucleophilic vinyl-gold moiety affords cyclopropenium intermediate II. Carboca-tion IV, which would finally collapse into cyclohexene 146 after elimination of the gold(I) catalyst might be generated via a [1,2]-alkyl shift on Au-carbene intermediate III. 

The more common processes are the activation of the alkyne fragment to yield alkynyl derivatives and the interaction with acids (H ) or related electrophilic species. 

As a working hypothesis it can be assumed, that Zn(II) participates in the complexa-tion and activation of the alkyne triple bond for subsequent cyclization via intermediates 11 and 12. The educts 9 are readily prepared [336] by dialkylzinc-assisted alkinyla-tion of nitrones.lt should be noted that N-Boc-O-propargyl hydroxylamines undergo Au(I)-catalyzed hydroaminative cyclization leading to 2,5-dihydroisoxazoles [337, 338]. 

With regard to the mechanism, three pathways are possible depending on the type of coordination of the metal to the enyne (Scheme 1.13). In the first pathway, the simultaneous coordination of the metal to the alkyne and alkene leads to the formation of 1,3- and 1,4-dienes through metaUacyclopentene intermediates (pathway a. Scheme 1.13). In this process, a two-electron oxidation of the metal takes place, which is favorable for palladium(O) and platinum(O), but highly unlikely for gold(l) under ordinary conditions. The second pathway is possible when the alkene motif bears a functional group that promotes the formation of a 7r-allylmetal intermediate (pathway b. Scheme 1.13). Finally, the third pathway is based on the selective activation of the alkyne moiety by the metal (pathway c. Scheme 1.13). 

The proposed mechanism involves initial Au(I) activation of the alkyne followed by nucleophilic addition to the alkyne by azide (Scheme 7.28). This is followed by loss of N2 to furnish a cationic intermediate, which is stabilized by electron donation from Au(I). A formal 1,2-hydrogen shift regenerates the Au(I) catalyst and the pyrrole after tautom-erization. A nitrene intermediate was deemed unlikely because Au(l) did not decompose azides that were not homopropargylic. Notably, Au(I) effectively acts as both a r-acid and electron donor an appropriate ligand environment is required to tune the electronic character of Au(l) for reaction success. 

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