Nobel Prize recognises chiral achievements

This year's Nobel Prize for Chemistry has been awarded to three synthetic organic chemists for their pioneering work on catalytic asymmetric synthesis. Barry Sharpless was cited for his work on chirally catalysed oxidation reaction, and William Knowles and Ryoji Noyori for their asymmetric hydrogenation chemistries.

Sharpless, based at the Scripps Institute in La Jolla, CA, US, has invented a collection of important asymmetric oxidation reactions, including epoxidations and dihydroxylations. The Sharpless epoxidation, discovered in 1980, uses titanium(IV) tetraisopropoxide, t-butyl hydroperoxide and a chiral dialkyl tartrate to epoxidate allyl alcohols in extremely high ee.

The tartrate directs the oxygen atom to either one face or the other of the substrate, depending on which isomer is used. This gives complete control over which stereoisomer is formed.

It is an excellent method of inducing chirality into achiral allyl alcohols. The subsequent discovery that the reaction proceeded equally well with catalytic amounts of tartrate if molecular sieves are added to the reaction mixture led to the process becoming industrially applicable.

The now-retired Knowles was responsible for the first industrial-scale catalytic asymmetric synthesis during his time at Monsanto. The Monsanto synthesis of L-dopa proved hugely successful. It uses a modification of Wilkinson's catalyst to give the stereospecific hydrogenation of α-amino acids.

Noyori, of Nagoya University in Japan, has created a variety of important chiral hydrogenation catalysts, many of which are used in industrial processes. The chiral diphosphine ligand BINAP was invented in 1980. In complexes with transition metals, notably Rh(I) and Ru(II), it is an extremely effective catalyst for the asymmetric hydrogenation of acrylic acids and esters to give amino acid derivatives.

Tweaking the ligand's structure and the reaction conditions mean a wide range of substrates can be hydrogenated stereoselectively, giving access to a huge variety of chiral building blocks and intermediates. Examples of commercial processes using Noyori's catalyst are the syntheses of the NSAID S-naproxen and the antibiotic levofloxacin.