Alkyne metathesis is anorganic reaction that entails the redistribution ofalkynechemical bonds. The reaction requires metal catalysts. Mechanistic studies show that the conversion proceeds via the intermediacy ofmetal alkylidyne complexes.[1][2][3] The reaction is related toolefin metathesis.
Metal-catalyzed alkyne metathesis was first described in 1968 by Bailey, et al. The Bailey system utilized a mixture of tungsten and silicon oxides at temperatures as high as 450 °C. In 1974 Mortreux reported the use of a homogeneous catalyst—molybdenum hexacarbonyl at 160 °C—to observe an alkyne scrambling phenomenon, in which an unsymmetrical alkyneequilibrates with its two symmetrical derivatives.[4]The Mortreux system consists of themolybdenum precatalystmolybdenum hexacarbonyl Mo(CO)6 andresorcinolcocatalyst. In 1975, T. J. Katz proposed a metal carbyne (i.e. alkylidyne) and a metallacyclobutadiene as intermediates. In 1981,R. R. Schrock characterized several metallacyclobutadiene complexes that were catalytically active.[5]
Molybdenum catalyst withaniline-derivedligands are highly effective catalysts.[6]
The so-called "canopy catalysts" containing tripodal ligands are particularly active and easy to prepare.[7][8] Thorough experimental and computational studies showed that metallatetrahedranes were isolable but dynamic species within the catalytic cycle.[9] Alkyne metathesis catalyst have also been developed usingrhenium(V) complexes.[10] Such catalysts are air stable and tolerant of diverse functional groups, includingcarboxylic acids.
Typical degradation pathways for these catalysts include hydrolysis and oxidation.
Dimerization of the alkylidyne units remains possible, as can be seen from complex 28, which was isolated in small amounts. In addition to the decomposition pathways by bimolecular collision or hydrolysis, Schrock alkylidyne complexes degrade upon attempted metathesis ofterminal alkynes. The critical step occurs after formation of themetallacycle and consists of atransannular C-H activation with formation of a deprotio-metallacyclobutadiene and concomitant loss of one alkoxide ligand. This reaction course remains viable for the new alkylidynes with silanolate ligands. Specifically, compound 29 could be isolated upon addition of 1,10-phenanthroline. As a result, terminal alkynes can not be metathesized under existing catalysis system with similar efficiency.[11]
In practice,5 Å MS is used asbutyne scavenger to shift the equilibrium to products.
Alkyne metathesis can be used inring-closing operations and RCAM stands for ring closing alkyne metathesis. Theolfactory moleculecivetone can be synthesised from a di-alkyne. After ring closure the new triple bond isstereoselectively reduced withhydrogen and theLindlar catalyst in order to obtain theZ-alkene (cyclicE-alkenes are available through theBirch reduction). An important driving force for this type of reaction is the expulsion of small gaseous molecules such asacetylene orbut-2-yne.
The same two-step procedure was used in the synthesis of the naturally occurringcyclophane turriane.
Trisamidomolybdenum(VI) alkylidyne complexes catalyze alkyne metathesis.[12]
RCAM can also be used as strategic step innatural product total synthesis.[13] Some examples show the power of these catalysts. For example, RCAM can serve as key step in total synthesis of marineprostanoid hybridalactone, whereepoxide,internal olefin and ester are tolerated.[14]
Another example shows a highly functionalizedenyne, which displays a rare thiazolidinone unit, can be metathesized under Mo(III) catalyst, neither this unusual sulfur-containing heterocycle nor the elimination-prone tertiaryglycoside posed any problem in the ring-closing step.[15]
The total synthesis of spirastrellolide F employs alkyne metathesis in one step.[16] The molecular frame of this potentphosphatase inhibitor is decorated with no less than 21 stereogenic centers and features a labile skipped diene in the side chain. Its macrocyclic core incorporates atetrahydropyran ring, a spiroketal unit, as well as a highly unusual chlorinated bis-spiroketal motif. Specifically, a sequence of RCAM coupled with a gold-catalyzedacetalization successfully build the polycyclic system at the late stage of the synthesis.
By replacing a tungsten alkylidyne by atungsten nitride and introducing anitrileNitrile-Alkyne Cross-Metathesis orNACM couples two nitrile groups together to a new alkyne. Nitrogen is collected by use of a sacrificial alkyne (elemental N2 is not formed):[17][18]
