Gold, that ubiquitous inert element turns out not to be so inert as one
might believe. For some years now gold has been successfully employed as a homogeneous catalyst in organic chemistry, catalysing some old and new reactions. This is due to the fact that Au(I) and Au(II) salts act as soft Lewis acids towards carbon.carbon double and triple bonds. Five years ago little was to be found about stereoselective gold catalysed reactions. But back in 1986 a first example appeared.
The complex catalyst used in 1mol% is based on a ferrocene structure used together with a gold tetrafluoroborate salt:
Depending upon the R group the trans/cis ratio varied between 80:20 and 100:0 with ee% of the trans lying between 72-97%, which is pretty good. However, this result was either ignored or forgotten by the community until the start of the new century when interest re-awakened. Now the chemistry developed since rely either on the transfer of chirality from a substrate with a defined configuration to the product, or on the introduction of chirality into a prochiral substrate through the use of chiral gold catalysts. A useful review can be found here.
Their soft Lewis acid properties have been useful in the activation of alkynes towards oxygen nucleophiles such as carbonyls, carboxylic acids and alcohols. However the gold catalysed cyclisation of enynols has not been widely investigated in spite of their use as valuable building blocks for the synthesis of bioactive molecules. Recently a new method for the construction of novel fused beta-lactams was reported using this methodology.
The conditions for this reaction are 2.5mol% of AuClPPh3, 2.5mol% of AgOTf, 10mol% of pTSA, 100mol% water in dichloromethane in a sealed tube at 80°C for 3 hours. The yield is 63% with a diastereoisomeric ratio of 60:40. The complex mixture of catalytic materials in this system is somewhat puzzling. However, it was shown by the authors that silver triflate alone does not catalyse the reaction. The actual catalyst may be Au(OTf)PPh3 generated in situ. There appears to be a complex catalytic cycle involved here and readers are referred to the original publication for more information.
So gold catalysis is now firmly established in the arsenal of organic chemistry, but as a comment in Nature this year pointed out it has been almost ignored by industry. Gold catalysts can be found in the catalytic converters of cars, Fiat in particular installed a gold converter in its diesel engined commercial vehicles. The catalyst converts carbon monoxide to carbon dioxide utilising atmospheric oxygen. The major contribution factor to the lack if industrial interest is, of course, the cost of the metal. However, gold has carved out it’s niche in organic chemistry and no doubt the future will show further successes.
