There are a number of papers that have described catalytic asymmetric C-H insertion reactions (see a recent review on catalytic intramolecular C-H aminations by Davies & Long), but there are only a few examples of asymmetric O-H insertion reactions. In the ASAP section of the Journal of the American Chemical Society, Maier & Fu reported the first “effective” method for catalytic enantioselective insertions into O-H bonds.
The authors showed that in the presence of copper and a chiral bisazaferrocene ligand, various alcohols reacted with methyl alpha-diazo-alpha-phenylacetate, yielding alpha-alkoxy esters (the best yields and ee were achieved using methanol, 2-trimethylsilylethanol, or para-methoxybenzyl alcohol). They further explored the scope of the reaction involving 2-trimethylsilylethanol and demonstrated that they could isolate a range of alpha-diazo-alpha-arylacetates in high yields and ee – since the trimethylsilylethyl group can be easily removed using boron trifluoride diethyl etherate, the authors could also obtain enantiomerically pure alpha-hydroxy esters in high yields and ee.
Joshua
Joshua Finkelstein (Associate Editor, Nature)
[Editor’s note – I’m fairly sure this comment was intended for the ‘Facing up to fullerenes’ entry and so it has been included there as well]
I have also been working with C60 for years, and to everyone I know it is accepted as pretty benign – you don’t worry at all about getting on your hands for example.
As to the substance behind the Zelens, there is actually a lot of scientific support for the antioxidant activity and safety. Notably, the fact that Merck licensed a water soluble C60 derivative in 2003 for continued study as a neurological antioxidant. There are literally dozens of patents and applications on the use of C60 compounds as antioxidants, and dozens more on the antioxidant activity. This all began at DuPont in about 1991 – where they showed the enormous capacity of a C60 to soak up fullerenes, and they coined the phrase “radical sponge” at that time. Not shoddy science, and it has been verified over and over again by leading scientists in peer-reviewed publications.
Mitsubishi has also been intensively studying the safe application of C60 compounds as antioxidants, and formed a company in Japan, Vitamin C60 Bioresearch, to market fullerene-containing skincare formulations. They’ve been doing quite well. They also have published several peer-reviewed articles on the safety.
So, knowing the literature quite well on the physiological application of C60 compounds – there is beyond the shadow of a doubt a great potential for the use of C60 as a safe antioxidant (a lot of toxicity data is out there), and believe it or not, Zelens is not the only product out there. Several more already exist in addition to Mitsubishi.
As to the recent Rice work, it is a travesty since they studied not C60 but 10 – 20 nm particles of C60, which has also been shown to have tetrahdrafuran inclusions which could have caused their observed oxidation of cell walls. A very recent publication from Japan duplicated their study using the same material as used in the Rice study but without THF, and they observed no adverse toxicity.
Whether Zelens or Mitsubishi actually have enough fullerenes in their product to actually do anything beneficial (or to be worth the money) is a different question, and I can’t vouch for either product.
By the way, the going price for pure C60 is about $25/g – just a shade higher than gold.