The Evans–Tishchenko reaction is the

diastereoselective In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have dif ...

reduction of β-hydroxy ketones to the corresponding 1,3-''anti'' diol mono

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

s. The reaction employs a Lewis acid, often samarium iodide, and an

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

. It was first described in 1990 by David A. Evans and Amir Hoveyda, as a development of the well-known

Tishchenko reaction The Tishchenko reaction is an organic chemical reaction that involves disproportionation of an aldehyde in the presence of an alkoxide. The reaction is named after Russian organic chemist Vyacheslav Tishchenko, who discovered that aluminium alkoxi ...

discovered in 1906. The Aldol–Tishchenko reaction provides another potential route to 1,3-diol monoester products.

Mechanism

The reaction mechanism involves the attack of the

from the free alcohol group. The Lewis acid can then

chelate Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...

between the two

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

atoms to form a cyclic, 6-membered

transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked ...

. The hydride, formerly the formyl hydrogen on the aldehyde, is delivered intramolecularly, accounting for the observed ''anti'' diastereoselectivity: the result is a 1,3-''anti'' diol mono

. The proposed mechanism is further supported by

isotopic labeling Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...

, which demonstrates that the formyl hydrogen is the one that migrates.

Scope and applications

The power of this reaction when compared to other methods of generating ''syn'' and ''anti'' diols, such as the Narasaka–Prasad reduction or the Evans–Saksena reduction, is the ability to differentiate between the two resulting hydroxyl groups, effectively selectively protecting one of them. For this reason, this reduction has been widely used in the literature, especially in the

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

of natural products.

References

{{DEFAULTSORT:Evans-Tishchenko reaction Name reactions