Fig. 1: Schematic illustration of a typical alkene (styrene) showing the C=C double bond, and the reaction scheme using copper triflate as a catalyst for the conversion of olefins to vicinal diols.
Alkenes, also known as olefins, are a class of organic molecules having at least one double bond between adjacent carbon atoms (C=C). Carbon–carbon double bonds are valuable because they can be converted into a wide range of other functionalities of chemical and pharmaceutical interest.
One such conversion is an oxidation reaction in which one of the C=C bonds is broken and two atoms of oxygen are added in its place to generate a ‘vicinal diol’ — a structural motif found in many naturally occurring chemical compounds and synthetic pharmaceutical drugs. The heavy metal compound osmium tetroxide is often used as a catalyst for this reaction but suffers from several drawbacks, not least its high price and notorious toxicity.
Jayasree Seayad and co-workers at the A*STAR Institute of Chemical and Engineering Sciences have now devised a method for successfully converting alkenes to a diacetoxy compound — a closely related derivative of vicinal diols — using a compound of copper known as copper(II) triflate as the catalyst (see Fig. 1). This copper salt is readily available, non-toxic and a fraction of the price of osmium tetroxide making the new method safe, cost-effective and environmentally benign.
In initial experiments, the researchers found that copper(II) triflate could catalyze the diacetoxylation of a common olefin known as styrene — the starting material for making polystyrene — in the presence of an oxidizing agent, PhI(OAc)2, and acetic acid, under mild conditions in high chemical yield and with few side products. Further experimentation established the generality of the reaction and allowed the researchers to extend the scope of the reaction to more structurally complex olefins.
The researchers also investigated the pathway by which the reaction proceeds and proposed a mechanism in which the copper enters the reaction in a form known as copper(II), which is then oxidized to an unusual and transient form of the metal called copper(III). This then cycles between it and another form known as copper(I) to generate the observed products. Interestingly, the A*STAR team discovered that a closely related class of substrates known as homoallylic alcohols bearing an existing hydroxyl group and a longer-chain alkene can be converted in to another useful class of cyclic organic molecules.
The improvements made to the alkene oxidation reaction by the use of cheap, low-toxicity copper salts and the mild conditions of the process open up the potential for its use in large-scale syntheses of vicinal diol derivatives. “We are also extending the scope of this method to the asymmetric synthesis of non-racemic diol derivatives, which will enable rapid access to the coveted chiral intermediates,” says Seayad.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Chemical and Engineering Sciences.
