Nav: Home

Partners in catalysis: An efficient route to unsaturated ketones

February 25, 2019

Kanazawa - In organic chemistry, discovering new reactions is one thing, but to carry them off efficiently is quite another. Carbon-carbon bond-forming is at the heart of organic synthesis, allowing us to stitch together diverse functional groups into an endless array of useful compounds. Now, Kanazawa University researchers have neatly streamlined one of the most important of those reactions.

Unsaturated ketones contain a C=O group and a C=C bond. If those two are separated by a CH2 group, the ketone is of the "beta-gamma" type. Logically enough, they can be made by reacting a C=O carbonyl with an allylic (C=C-containing) alcohol. However, in the usual route, these must be pre-activated with a metal and an organic leaving group, respectively, which is laborious and costly.

"React an aldehyde directly with an alcohol, and you do away with the expensive pre-activation," says Hirohisa Ohmiya, leading author of the study, published in Chemistry: A European Journal. "As an added benefit, the by-product is merely water, formed by expelling an H atom and an OH group. Unfortunately, the carbon atoms that we need to react normally repel each other, because they are both positively charged."

However, as the study shows, the dehydrative (water-releasing) reaction can be stimulated by a classic trick in the chemist's arsenal: umpolung, or reversing the polarity. The normally electrophilic (positive) C=O carbon is transformed via catalysis. Primed by the electron density donated from an N-heterocyclic carbene (NHC) catalyst, the carbonyl becomes a negatively charged nucleophile, ready to react with the electrophilic alcohol.

Both aldehydes and allylic alcohols are easily available, and the Kanazawa team synthesized a diversity of products in good yield. Many biological compounds are beta-gamma unsaturated ketones--for example, the team produced a steroid derivative through selective reaction of the desired steroid C=O group. This class of ketones is also an important stop on the route to larger molecules.

While the NHC catalyst prepares the carbonyl substrate for the reaction, a second catalyst is needed to activate the alcohol. This phosphine-bound palladium complex, generated in situ during the reaction, forms a cation that undergoes allylation with the negatively charged NHC/carbonyl anion. The combination of catalysts is a neat example of synergistic cooperation during a reaction.

"This will undoubtedly make beta-gamma unsaturated ketones much more accessible," says lead author Hirohisa Ohmiya. "Chemists have a responsibility to the environment like everyone else, so the lack of by-products and the economical nature of the reaction will be major assets when scaled-up to industry. Our next challenge is to devise a chirally selective version for asymmetric synthesis."

Kanazawa University

Related Alcohol Articles:

This is your brain on alcohol (video)
It's almost time to ring in 2017. And since most New Year's celebrations include alcohol, Reactions' latest episode explains the chemistry behind its effects -- drunkenness, frequent bathroom breaks and occasionally poor decision-making.
Heavy alcohol use changes adolescents' brain
Heavy alcohol use during adolescence alters the development of brain, according to a recent study from the University of Eastern Finland and Kuopio University Hospital.
Maryland's 2011 alcohol sales tax reduced alcohol sales, study suggests
Maryland's 2011 increase in the alcohol sales tax appears to have led to fewer purchases of beer, wine and liquor in the state, suggesting reduced alcohol use, new Johns Hopkins Bloomberg School of Public Health research indicates.
Alcohol related deaths are likely to increase after cuts in alcohol taxation
Alcohol related deaths are most likely set to increase in England as incomes outstrip rises in taxation, argue experts in The BMJ today.
Alcohol aromatherapy eases nausea in the ER
Nauseated patients in the emergency department who sniffed pads saturated with isopropyl alcohol were twice as likely to obtain relief from their symptoms as nauseated patients who sniffed pads saturated with saline solution, according to a study published online today in Annals of Emergency Medicine ('Isopropyl Alcohol Nasal Inhalation for Nausea in the Emergency Department: A Randomized Controlled Trial').
Alcohol ads linked to teen alcohol brand choices
Overall exposure to brand-specific alcohol advertising is a significant predictor of underage youth alcohol brand consumption, with youth ages 13 to 20 more than five times more likely to consume brands that advertise on national television and 36 percent more likely to consume brands that advertise in national magazines compared to brands that don't advertise in these media.
Should women consume alcohol during pregnancy?
In The BMJ this week, experts discuss the evidence and current guidelines on the controversial topic of alcohol consumption during pregnancy.
The Lancet: Harmful alcohol use linked with increased risk of alcohol-related cancers and injury
A new study of alcohol use in countries of all income levels shows that current use increases the risk of alcohol-related cancers and injury, with no reduction in risk of mortality or cardiovascular disease overall.
Web interventions for alcohol misuse
A systematic evidence review published in Annals of Internal Medicine finds that low-intensity electronic interventions may slightly reduce alcohol consumption among adults and college students, but may be ineffective for reducing binge-drinking frequency and the negative social consequences associated with alcohol misuse.
Marijuana users substitute alcohol at 21
A recent study looked at marijuana and alcohol use in people between the ages of 18 and 24.

Related Alcohol Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".