Alkynes addition reaction catalyzed

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markownikoff rule. Internal alkynes will give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to / -acetoxy- or /i-mcthoxyalk-enylmercury intermediates.116 These intermediates can be reduced to alkenyl acetates or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate which is opened by nucleophilic attack at the more positive carbon that is, the additions follow the Markownikoff rule. Scheme 4.7 gives some examples of alkyne addition reactions. 

In 2008, Li et al. reported a copper-catalyzed amine-alkyne-alkyne addition reaction as an efficient method for the synthesis of Y,5-alkynyl-p-amino acid derivatives 102 (Scheme 3.52) [137]. In this case, the first step of the reaction is proposed to be the hydroamination of the electron-deficient alkyne 100, which plays the role of the aldehyde component. Subsequent reaction of the resultant intermediate XXX with alkyne 101 would afford intermediate XXXI, which would be then protonated to give an iminium intermediate XXXII. Finally, an intramolecular transfer of the alkyne moiety to the iminium ion would yield the 7,8-alkynyl-p-amino ester 102 and regenerate the catalyst. The reaction was later extended using chiral prolinol derivatives as the amine component, which afforded the corresponding Y,5-alkynyl-p-amino acid derivatives with excellent diaste-reoselectivities (up to >99 1) [138]. 

L. Zhou, H.-F. Jiang, C.-J. Li, Adv. Synth. Catal. 2008, 350, 2226-2230. Efficient synthesis of y,8-alkynyl- 3-amino acid derivatives by a new copper-catalyzed amine-alkyne-alkyne addition reaction. 

Alkynes react when heated with trifluoroacetic acid to give addition products. Mixtures of syn and anti addition products are obtained. Similar addition reactions occur with trifluoromethanesulfonic acid. These reactions are analogous to acid-catalyzed hydration and proceed through a vinyl cation intermediate. 

The addition of terminal alkynes to carbon-carbon double bonds has not been explored until recently, possibly because C=C double bonds are not as good electrophiles as C=N or C=0. In 2003, Carreira et al. reported the first conjugate addition reaction of terminal alkynes to C=C catalyzed by copper in water. The reaction proceeded with derivatives of Meldrum s acid in water in the presence of Cu(OAc)2 and sodium ascorbate (Eq. 4.35).59 However, this method was limited to C=C double bonds with two electron withdrawing groups. 

On the other hand, Li et al. reported the first palladium-catalyzed 1,4-addition of terminal alkynes to vinyl ketones in water with high yields (Eq. 4.36).60 At nearly the same time, Chisholm et al. reported such a reaction catalyzed by Rh(acac)(CO)2 (acac = acetylacetonoate) in the presence of /m(o-mcthoxyphcnyl)phosphine in aqueous dioxane... 

A few additional Pd-catalyzed schemes have been employed for Ilac type cyclization chemistry. Palladium-phenanthroline complexes were used by the Ragaini group to prepare indoles via the intermolecular cyclization of nitroarenes and alkynes in the presence of carbon monoxide <06JOC3748>. Jia and Zhu employed Pd-catalysis for the annulation of o-haloanilines with aldehydes <06JOC7826>. A one-pot Ugi/Heck reaction was employed in the preparation of polysubstituted indoles from a four-component reaction system of acrylic aldehydes, bromoanilines, acids, and isocyanides <06TL4683>. 

Addition Reactions of Alkynes Catalyzed by Gold Complexes 266... 

In the course of investigation into new C-C bond formation processes, Hiyama has developed an efficient nickel-catalyzed arylcyanation of alkynes.67 The addition reaction of an aryl-CN bond to alkyne affords aryl-substituted alkene nitrile in good yield. Good regioselectivity is reported in the case of unsymmetrical alkynes with two sterically different substituents. 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

Palladium-catalyzed addition of the selenium-silicon bond of PhSe-SiMe3 to arylacetylenes proceeds in a regio- and stereoselective manner to afford (Z)-a-(phenylseleno)-/ -(trimethylsilyl)styrenes (Equation (123)).250 Aliphatic alkynes fails to undergo the addition reaction. Analogous addition of the Se-Ge bond to alkynes occurs under similar conditions. 

Whereas zirconium-catalyzed alkylalumination of alkynes is at present limited to some simple alkyl groups, it has been found that carbozirconation with Cp2Zr(R)Cl considerably expands the scope of the alkylmetalation of alkynes. The reactions are initiated by catalytic amounts of additives (typically Ph3C[B(C6F5)4]), which probably serve to generate cationic zirconocene species. Regioselectivity in favor of attack at the more highly substituted carbon is observed [70,71] (Scheme 8.35). 

The hydrostannation of alkenes and alkynes can be catalyzed by a number of transition metals (Ni, Pd, Pt, Mo, etc.), but most studies have involved palladium.106 The mechanism that is most commonly accepted is shown for an alkyne in Scheme 1 the model for an alkene is similar. This mechanism accounts for the observations that the reactions normally involve cir-addition, that the R3Sn group enters so as to avoid steric hindrance by the largest substituent group on the alkene or alkyne, and that the regioselectivity depends on the polarization of the palladium-hydrogen bond in the sense Pd -H15-. 

Phosphonium salts can be synthesized by the transition-metal-catalyzed addition reaction of triaryphosphines and acids to unsaturated compounds. The reaction of PPh3, CH3SO3H, and alkynes in the presence of a palladium or rhodium catalyst gave alkenylphosphonium salts. Although Pd(PPh3)4 directed the C-P bond formation at the internal carbon atom of aliphatic 1-alkynes (Markovnikov mode), [RhCl(cod)]2... 

In comparison with the hydroboration and diborafion reactions, thioboration reactions are relatively limited. In 1993, Suzuki and co-workers reported the Pd(0)-catalyzed addition of 9-(alkylthio)-9-BBN (BBN = borabicyclo [3.3.1] nonane) derivatives to terminal alkynes to produce (alkylthio)boranes, which are known as versatile reagents to introduce alkylthio groups into organic molecules [21], Experimental results indicate that the thioboration reactions, specific to terminal alkynes, are preferentially catalyzed by Pd(0) complexes, e.g. Pd(PPh3)4, producing (thioboryl)alkene products, in which the Z-isomers are dominant. A mechanism proposed by Suzuki and co-workers for the reactions involves an oxidative addition of the B-S bond to the Pd(0) complex, the insertion of an alkyne into the Pd-B or Pd-S bond, and the reductive elimination of the (thioboryl)alkene product. 

In fact, a mechanism for this reaction can be drawn that does not involve Pd at all, but let s assume that Pd is required for it to proceed. Cl- must be nucleophilic. It can add to Cl of the alkyne if the alkyne is activated by coordination to Pd(II). (Compare Hg-catalyzed addition of water to alkynes.) Addition of Cl- to an alkyne-Pd(II) complex gives a o-bound Pd(II) complex. Coordination and insertion of acrolein into the C2-Pd bond gives a new a-bound Pd(II) complex. In the Heck reaction, this complex would undergo P-hydride elimination, but in this case the Pd enolate simply is protonated to give the enol of the saturated aldehyde. 

These critical aspects of the classical fluorous biphasic catalysis led in recent works to the development of protocols for the conversions with modified catalyst systems in non-fluorinated hydrocarbons as solvents. As part of the BMBE lighthouse project, Gladyzs and coworkers appHed this concept to C - C coupHng reactions (Suzuki reaction) and other metal-catalyzed addition reactions (hydrosilylation, selective alcoholysis of alkynes), which have direct relevance for the synthesis of fine chemicals and specialties [74]. 

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