2021 Nobel Prize in Chemistry
Reason for Award
for the development of asymmetric organocatalysis
Laureates
Germany
United Kingdom of Great Britain and Northern Ireland, 
United States of America
Explanation
Chemists build molecules like connecting LEGO bricks, but sometimes they get two mirror-image versions, like right and left hands. Benjamin List and David MacMillan discovered a “magic tool” that uses ordinary organic molecules, not metals, to choose which hand-shaped molecule to make. A tiny amount of an amino acid called proline, for example, speeds up the reaction and lets only the desired shape grow. This means medicines can be produced with less waste and in a way that is kinder to the environment.
Related Keywords
asymmetric synthesis
A synthetic strategy that selectively produces only one of two mirror-image isomers. It is vital in pharmaceuticals and fragrances to obtain the desired biological activity. Organocatalysts offer a metal-free alternative to enzymes and traditional catalysts, often shortening multistep routes by several stages.
organocatalyst
A small molecule with a carbon framework that accelerates reactions without metals. Examples include proline, imidazolidinones and thioureas. They are environmentally benign, easy to handle and, when chiral, provide high enantioselectivity.
proline
A naturally occurring amino acid with a cyclic structure that confers rigidity. List used it to catalyze enantioselective aldol reactions via the enamine mechanism, forming new C–C bonds. It is inexpensive, operates in water, and has become an icon of green chemistry.
iminium ion
A cation formed when a secondary amine condenses with an aldehyde or unsaturated carbonyl compound, increasing electrophilicity. MacMillan catalysts form iminium ions to accelerate Diels–Alder and Michael additions with high enantioselectivity.
enamine
A π-conjugated nucleophile formed by dehydration of a secondary amine with a carbonyl compound. It enables C–C bond formation at the carbonyl α-position and is a key intermediate in enantioselective aldol and Mannich reactions.
cascade reaction
A strategy in which several reactions proceed sequentially in the same vessel without isolating intermediates. It greatly improves material and time efficiency. Organocatalysts, with their mild conditions and low side-reactions, are well suited for cascade processes.
green chemistry
A philosophy that seeks to minimize environmental impact in chemical synthesis. Organocatalysts, which generate no metal waste and often work under ambient conditions, are exemplary tools of green chemistry and attract widespread industrial interest.
pharmaceutical synthesis
The large-scale production of drugs requires high purity and selectivity. Organocatalysts shorten manufacturing routes and reduce solvent and energy consumption. Improved syntheses of paroxetine and sitagliptin are notable examples.
chirality
A property of molecules that cannot be superimposed on their mirror images. Because enzymes and receptors are chiral, biological activity can differ drastically between enantiomers. Organocatalysts enable cost-effective control of chirality.
catalytic cycle
A loop diagram that shows how a catalyst passes through intermediates and is regenerated. In organocatalysis, typical cycles include enamine formation → nucleophilic attack → hydrolysis. Mapping cycles accelerates the design of new catalysts.