Copper catalyst distinguishing two different carbonyl compounds -- synthesis of 1,2-diols

March 05, 2019


1,2-Diols*1) are common scaffolds in many pharmaceuticals, agrochemicals, and natural products. The most direct method of synthesis would be if two easily obtainable carbonyl*2) compounds as starting materials would be converted into a 1,2-diol by carbon-carbon bond formation between the two compounds by reductive coupling. However, since conventional methods need very harsh conditions for such a reaction, it is difficult to distinguish between the two carbonyls, e.g., A and B, and such a reaction would give three species of 1,2-diols, i.e. AB, AA and BB (Figure 1). This means that a complex procedure to separate three species of 1,2-diols is necessary.

[Outline of research results]

The present research team of Kanazawa University, including two students, was successful in selectively synthesizing one species of 1,2-diol from an aldehyde and a ketone, both of which are carbonyl compounds, as the starting materials (Figure 2). The key to the success was a newly developed copper catalyst that could distinguish between the two different carbonyl compounds, activate each compound in a different manner and connect two different compounds to selectively yield a 1,2-diol. Copper is abundantly available and since its toxicity is not so high it is considered to be friendly to both humans and the environment. It was important to use N-heterocyclic carbene*3) as the ligand*4) to the copper catalyst.

More specifically, the copper catalyst makes the following two processes, 1 and 2, take place sequentially (Figure 3).

  1. After addition of silylcopper species to an aldehyde and the subsequent transfer reaction, an active copper species equivalent to a hydroxycarbanion*5) is catalytically generated.

  2. The active copper species thus formed is captured by a ketone.

By using a chiral*6) N-heterocyclic carbene as the ligand to the copper catalyst, the team has also succeeded in asymmetric synthesis*7) of chiral 1,2-diols.

[Future prospect]

In this study, the team has developed a new copper catalyst that could distinguish between two different carbonyl compounds and form a carbon-carbon bond to connect them, yielding one species of 1,2-diol. This type of selective synthesis was known to be quite difficult; the present success should open up a way for organic synthesis of 1,2-diol chemicals. It is expected to lead to a rapid synthesis of pharmaceuticals, agrochemicals, and natural products of complex structure.

*1) 1,2-Diol
A compound whose two vicinal carbon atoms have hydroxyl groups.

*2) Carbonyl
A functional group with a double bond between a carbon atom and an oxygen atom.

*3) Carbene
A carbene is a twofold coordination chemical species containing a neutral carbon atom with only six valence electrons.

*4) Ligand
A ligand is an organic molecule that binds to a central metal atom.

*5) Carbanion
A carbanion is a chemical species in which carbon bears a negative charge.

*6) Chiral
Chirality is a geometric property of some molecules and ions, and a chiral molecule/ion is non-superimposable on its mirror image, just like our right and left hands. A number of chiral molecules, enantiomers, can be found in the world of chemistry, while their constituting atoms and alignment are the same. Chiral molecules have similar chemical/physical properties while biological functions are sometimes quite different.

*7) Asymmetric synthesis
Asymmetric synthesis is a synthetic chemical reaction that selectively synthesizes one of the chiral molecules, usually a useful one.

[Special note]

This article is used for the Supplementary Cover of JACS February 27 (2019) issue.

Kanazawa University

Related Pharmaceuticals Articles from Brightsurf:

A plot twist in pharmaceuticals: Single nanoparticles could pave the way for medicines on demand
For the first time, a single, twisted nanoparticle has been accurately measured and characterised in a lab, taking scientists one vital step closer to a time when medicines will be produced and blended on a microscopic scale.

New pharmaceuticals: public research combines efficiency with contained costs
Is the basic research that goes into the development of new drugs more efficiently conducted by public-sector scientists, pharmaceutical firms, or independent private laboratories?

New STM technique points way to new and purer pharmaceuticals
A research project led by chemists at the University of Warwick first used ultrahigh resolution scanning tunnelling microscopy to see the exact location of atoms and bonds within a molecule, and then employed these incredibly precise images to determine the interactions that bond molecules to one another.

Study describes cocktail of pharmaceuticals in waters in Bangladesh
An analysis revealed that water samples held a cocktail of pharmaceuticals and other compounds, including antibiotics, antifungals, anticonvulsants, anesthetics, antihypertensive drugs, pesticides, flame retardants and more.

Treating wastewater with ozone could convert pharmaceuticals into toxic compounds
With water scarcity intensifying, wastewater treatment and reuse are gaining popularity.

Study calls for improved sanitation and the environmental management of pharmaceuticals
Failure to ensure the environmental sustainability of growing patient access to medicines in developing economies could increase the risk of adverse environmental impacts, according to new research led by the University of Plymouth.

Chemicals for pharmaceuticals could be made cheaper and greener by new catalysts
High value chemicals used to make pharmaceuticals could be made much cheaper and quicker thanks to a series of new catalysts made by scientists at the University of Warwick in collaboration with GoldenKeys High-Tech Co., Ltd. in China.

Soaking up pharmaceuticals and personal care products from water
Medications excreted in the urine or dumped into the toilet can end up in the water supply, just like lotions or cosmetics that wash off the body and go down the sink or shower drain.

New study finds river wildlife contain cocaine, pharmaceuticals and pesticides
For the first time, researchers at King's College London, in collaboration with the University of Suffolk, have found a diverse array of chemicals, including illicit drugs and pesticides in UK river wildlife.

Metal-free catalyst to convert aldehyde into ketone, a basic structure of pharmaceuticals
We succeeded in synthesizing a ketone, a basic structure of many pharmaceuticals, from an aldehyde and a carboxylic acid using N-heterocyclic carbene catalyst under mild conditions.

Read More: Pharmaceuticals News and Pharmaceuticals Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to