Thermodynamic alkyne metathesis

Alkyne metathesis, a mechanistic cousin of alkene metathesis, has thus far found only limited exploration. In 2004, Zhang and Moore reported that precipitation-driven alkyne metathesis reactions could efficiently produce arylene ethynylene macrocycles [50]. This was explored further in a 2005 report, verifying that the products obtained were indeed the result of thermodynamic self-selection [51]. 

The most recent method developed for the nA —> An approach relies on dynamic covalent bond formation using a metathesis reaction. In this case, reactions are typically under thermodynamic control, providing the potential for increased selectivity in product formation. The initial examples using alkyne metathesis toward the formation of SPMs were reported by Adams, Bunz, and coworkers using the precatalyst [Mo(CO)6] [27,28], but rather low yields of the desired products (4) limited general applicability (Scheme 6.2). Recent efforts by Moore and coworkers using a Mo(VI)-alkylidyne catalyst, however, have refined this process such that precipitation-driven reactions now provide moderate to excellent results (see Scheme 6.24) [29]. 

Naturally, the question arises What accounts for the dramatic difference in yields between these processes Macrocyclization under kinetic control, as shown by the Staab example, is clearly not a favorable situation, as evidenced by the low yield of 14a. In contrast, it has been shown that when alkyne metathesis macrocyclization is under thermodynamic control, [n]cycles are the lowest-energy product [64]. ADIMAC of monomer 15a under the conditions shown in Scheme 6.8 generate [6]cycle 16 as the major product, and [5]cycle 17 as a minor product. Gel permeation chromatography (GPC) analysis confirmed that the oligomeric products (both linear and cyclic) that are initially formed in the reaction are consumed over time, and the [5-6]cycles are the major product upon completion. More dramatically, when polymer 15b was subjected to the same conditions, the major products... 

Olefin metathesis reactions cleave carbon-carbon double bonds and reassemble tiiem to generate products containing new carbon-carbon double bonds. This process requires a catalyst and is largely controlled by thermodynamics (Equation 21.1). Alkyne metathesis reactions cleave carbon-carbon triple bonds and reassemble them to form products containing new carbon-carbon triple bonds (Equation 21.2). The observation of complete cleavage of strong carbon-carbon multiple bonds by a catalytic process was remarkable when first discovered, but many transition metal complexes are now known that catalyze these reactions with fast rates. One might expect that the equilibrium control of this reaction would limit its use, but olefin metathesis has become one of the most useful reactions catalyzed by transition metal complexes. 

Treatment of an alkyne/alkene mixture with ruthenium carbene complexes results in the formation of diene derivatives without the evolution of byproducts this process is known as enyne cross-metathesis (Scheme 22). An intramolecular version of this reaction has also been demonstrated, sometimes referred to as enyne RCM. The yield of this reaction is frequently higher when ethylene is added to the reaction mixture. The preferred regiochemistry is opposite for enyne cross-metathesis and enyne RCM. The complex mechanistic pathways of Scheme 22 have been employed to account for the observed products of the enyne RCM reaction. Several experiments have shown that initial reaction is at the alkene and not the alkyne. The regiochemistry of enyne RCM can be attributed to the inability to form highly strained intermediate B from intermediate carbene complex A in the alkene-first mechanism. Enyne metathesis is a thermodynamically favorable process, and thus is not a subject to the equilibrium constraints facing alkene cross-metathesis and RCM. In a simple bond energy analysis, the 7r-bond of an alkyne is... 

In addition to the metathesis of olefins, metathesis between an olefin and an aUcyne and metathesis between two alkynes are known and can be synthetically valuable. The metathesis between an olefin and an alkyne is called en)me metathesis, and enyne methathesis is the final class of reaction involving an alkene shown in Scheme 21.1. This process combines an olefin with an alkyne to generate a diene. The thermodynamic driving force for this process is created by tire generation of a new carbon-carbon single bond from the cleavage of one of the ir-bonds in an alkyne. 

Despite their high dissociation energy of 133 kcal/mol, sp C—H bonds are prone to C—H bond activation. Indeed, the simplest alkyne, acetylene, has a rather small pR, value of25—26, which makes it a weak acid in organ-ometaUic chemistry, and can be deprotonated by a strong base such as a nitrogen- or carbon-based anion. Therefore, the reaction between a metal alkyl complex and a primary alkyne is usually thermodynamically favorable and resembles a classical acid—base metathesis reaction. 

---