Alkyne reactions, mechanism

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 original Sonogashira reaction uses copper(l) iodide as a co-catalyst, which converts the alkyne in situ into a copper acetylide. In a subsequent transmeta-lation reaction, the copper is replaced by the palladium complex. The reaction mechanism, with respect to the catalytic cycle, largely corresponds to the Heck reaction.Besides the usual aryl and vinyl halides, i.e. bromides and iodides, trifluoromethanesulfonates (triflates) may be employed. The Sonogashira reaction is well-suited for the synthesis of unsymmetrical bis-2xy ethynes, e.g. 23, which can be prepared as outlined in the following scheme, in a one-pot reaction by applying the so-called sila-Sonogashira reaction ... 

With respect to reaction mechanism, it is likely that CpCo(CO)2-mediated alkyne cyclotrimerizations proceed through discrete orga-nometallic intermediates and are therefore not concerted.12 A plausible mechanistic pathway for the CpCo(CO)2-catalyzed cyclotri-... 

For the cyclotrimerization of alkynes, several mechanisms have been proposed. The most plausible ones are a concerted fusion of three ir-bonded alkyne molecules, and stepwise processes involving a cyclobutadiene complex or a five-membered metallocyclic intermediate (98). In the case of the cyclotrimerization of a-alkynes it is possible to discriminate between a reaction pathway via a cyclobutadiene complex and the other reaction pathways, by analysis of the products. If cyclotrimerization proceeds via a cyclobutadiene complex and if steric factors do not affect the reaction,... 

In a remarkable reaction according to Eq. 18 palladium(II) acetate reacts in methanol with diphenylacetylene to form dinuclear [Pd(T 5-C5Ph5)]2(p-PhC = CPh) (67) [79], The reaction mechanism was studied in some detail and part of the alkyne molecule was found as benzoic acid orthoester PhC(OMe)3. When... 

Since activation of the N-H bond of PhNHj by Ru3(CO)i2 has been reported to take place under similar conditions [306], it has been proposed that the reaction mechanism involves (i) generation of an anUido ruthenium hydride, (ii) coordination of the alkyne, (iii) intramolecular nucleophilic attack of the nitrogen lone pair on the coordinated triple bond, and (iv) reductive ehmination of the enamine with regeneration of the active Ru(0) center [305]. 

The proposed reaction mechanism (Scheme 7-2) comprises (1) oxidative addition of ArSH to RhCl(PPh3)3 to give Rh(H)(Cl)(SPh)(PPli3)n, (2) coordination ofalkyne to the Rh complex, (3) ris-insertion of alkyne into the Rh-H bond with Rh positioned at terminal carbon and H at internal carbon, (4) reductive elimination of 16 from the Rh(III) complex to regenerate the Rh(I) complex. 

Although the path (a) has been verified by a stoichiometric reaction [23], the details of exact reaction mechanism remain unsettled. Triggered by this publication [and the Pd-catalyzed doublethiolation of alkynes described in Eq. (7.7) in Section 7-3], a number of transition metal-catalyzed additions of S-X or Se-X bonds to C-C unsaturated organic compounds started to be published. In 1994, BackvaU et al. applied the Pd(OAc)2-catalyzed hydrothiolation to conjugated enynes and obtained 17,... 

The regioselective preparation of 2-substltuted naphthalenediol derivatives having the diols differentially protected in a predictable and straightforward manner, previously not directly attainable, is readily accomplished using chromium carbene complexes. First prepared by E. O. Fischer, chromium carbene complexes react readily with alkynes (extensively investigated by K. H. D6tz, and others).3 Steric effects dictate the substitution pattern observed2-4 and the reaction mechanism has been widely studied.2... 

Catalytic coupling reaction of aldehydes, alkynes, and secondary amines promoted by less than 3 mol.% of Ag(l) salt was reported by Li et al,517 In this reaction, pure water was used as solvent and Agl was found to be the best catalyst without need of any additives or co-catalysts (Table 9). The reaction mechanism has been proposed as shown in Scheme 110. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

The final cyclization manifold has been realized with a different ruthenium catalyst (Scheme 22). The cationic [Cp Ru(MeCN)3]PF6 induces exclusive endo-dig cyclization of both homopropargylic and bis-homopropargylic alcohols.29 73 The clean reaction to form a seven-membered ring is noteworthy for several reasons intramolecular exo-dig cyclization with bis-homopropargylic alcohols is not well established, the platinum-catalyzed case has been reported to be problematic,80 and the selectivity for seven-membered ring formation over the exo-dig cyclization to form a six-membered ring is likely not thermodynamic. The endo-dig cyclization manifold was thus significant evidence that a re-examination of alkyne hydrosilylation mechanisms is necessary (see Section 10.17.2). 

The reaction mechanism was considered to be oxidative cyclization, and pal-ladacyclopentene 32 was formed. Reductive elimination then occurs to give cyclobutene 33, whose bond isomerization occurs to give diene 28. The insertion of alkyne (DMAD) into the carbon palladium bond of 32 followed by reductive elimination occurs to give [2+2+2] cocyclization product 27. Although the results of the reactions of E- and Z-isomers of 29 with palladium catalyst 26a were accommodated by this pathway, Trost considered the possibility of migration of substituents. Therefore, 13C-labeled substrate 25 13C was used for this reaction. 

In 1978, Negishi et al. reported highly regio- and stereoselective methylalumination of alkynes with Me3Al using a zirconocene catalyst [59]. The involvement of cationic zirconocene species in the activation of carbon—carbon triple bonds was suggested in a reaction mechanism featuring electrophilic activation by aluminum (Scheme 8.30). 

Attempts to use the isobutyl group in the carbometalation of alkynes only give rise to hy-drometalated products, but ethyl and n-propyl groups can be successfully transferred from the corresponding dialkylaluminum chlorides. The regioselectivity in these reactions is lower than that for the methyl transfer. Indeed, the reaction mechanism may be different from that of methylalumination [62]. 

Figure 9. The reaction mechanism of Pt(0)-catalyzed alkyne and alkene diboration reactions calculated by Morokuma and co-workers.

For the diboration reactions of alkynes catalyzed by Pt(0) complexes, the reaction mechanism involves the oxidative addition of diborane to the Pt(0) center, followed by the insertion of alkyne into the Pt-B bond and reductive... 

For the thioboration reactions of alkynes preferentially catalyzed by Pd(0) instead of Pt(0), the reaction mechanism involves a metathesis-like process. The reason for not having an oxidative addition step can be related to the electron richness of the alkylthio group, which prevents the oxidative addition of thioborane to the metal center. Because of the preference for having a metathesis-like process, Pd becomes a better candidate due to its relative less electron richness in comparison to Pt. 

Dotz reaction is proposed. According to our calculations the addition of the alkyne molecule to the carbene complex takes place before CO loss in the initial steps of the reaction. Further, our study shows that a novel proposal involving a chromahexatriene intermediate entails lower energy barriers and more stable intermediates than the previous reaction mechanisms postulated by Dotz and Casey. The novel findings query revision of the classically assumed paths and put forward that additional experimental and theoretical studies are necessary to definitely unravel the reaction mechanism of this intringuing reaction. 

The Dotz reaction mechanism has received further support from kinetic and theoretical studies. An early kinetic investigation [37] and the observation that the reaction of the metal carbene with the alkyne is supressed in the presence of external carbon monoxide [38] indicated that the rate-determining step is a reversible decarbonylation of the original carbene complex. Additional evidence for the Dotz mechanistic hyphotesis has been provided by extended Hiickel molecular orbital [23, 24] and quantum chemical calculations [25],... 

This section describes the main results obtained in our studies of the Dotz reaction mechanism [26-29, 39]. The section is divided as follows First, the results for the initial part of the reaction (9—>13) are presented. The central discussion will be whether the alkyne binds the carbene complex after or before CO loss. Then, the results for routes A, B and C (Figure 3) are discussed. In particular, we will examine the suitability of the novel route C involving a chromahexatriene intermediate. 

Difluorophosphoryl(trifluoromethyl) peroxide, 16 135, 136 reactions of, 16 136 Difluoropolysulfanes, 16 302, 325-327 NMR of, 16 325, 326 separation of, 16 327 Difluorosilylene, 29 15-36 alternate layer reactions, 29 26-27 in nuclear recoil systems, 29 22 polymerization, 29 15 reaction mechanisms with alkenes and alkynes, 29 17-19 under co-condensation conditions, 29 28-32, 34-35... 

The proposed reaction mechanism is shown in Scheme 9.15. Starting from the phenyl-rhodium complex 87, alkyne rearrangement is expected to furnish the phenyl-vinylidene complex 88. Migration of a phenyl ligand onto the vinylidene moiety of 88 must occur such that the vinyl Rh-C bond and the enone tether of the resultant complex (89) attain a cis-relationship to one another. Intramolecular conjugate... 

The intermediacy of a platinum vinylidene in Yamamoto s reaction was supported by the results of isotopic labeling studies. D FT calculations were used to further probe the proposed reaction mechanism. In contrast to the prevailing model of alkyne/ vinylidene interconversion for Rh(I)-catalysts, direct Ca Cp 1,2-H-migration is implicated in the formation of vinylidene 130. Direct C—H insertion via a single... 

Presumably, these skeletal reorganization reactions start by coordination of a metal ion to an alkyne part in 78 to allow an alkene part to attack the resulting electrophilic alkyne carbon coordinated by the metal. However, the reaction mechanism remains yet to be clarified, and it is thought that each reaction mechanism differs depending on the metal used. 

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