- Press Release Distribution

Privileged strategies for direct transformations of inert aliphatic carbon-hydrogen bonds

Privileged strategies for direct transformations of inert aliphatic carbon-hydrogen bonds
( Functional group transformations are central to organic synthesis. Traditionally, the functionalities used in such transformations are highly active organic groups such as halogens, ester groups and hydroxyl groups. Carbon–hydrogen bonds are ubiquitous structural motifs in organic compounds, but they are not considered to be functional groups because (1) in general, the bond dissociation energy of a C–H bond is high, and therefore, such bonds are thermodynamically hard to break; and (2) the selective activation of one C–H bond among many similar and different C–H bonds in one organic molecule is difficult. However, direct C–H transformations, which could be used to perform synthetic chemistry in a greener and more atom-economical way, are highly appealing. The importance and challenges of this field make it one of the 'Holy Grails' of chemistry.

Guihua Chen and Zhang-Jie Shi, scientists at the College of Chemistry and Molecular Engineering, at Peking University in the Chinese capital, account progress and challenges in this area, "Privileged strategies for direct transformations of inert aliphatic C–H bonds," published in the Beijing-based journal National Science Review.

"In the last few decades, direct C(sp2)–H activation of (hetero)arenes and some alkenes has been extensively investigated," they state in the study. "Many examples and applications of such activations in organic synthesis have been reported. Some progress has also been made in achieving the direct transformation of relatively active benzylic and allylic C–H bonds. In contrast, less effort has been devoted to the activation of 'inert' aliphatic C–H bonds of alkyl groups, because the challenge is greater. The acidity of an alkyl C(sp3)–H bond is lower than those of other C–H bonds, making the cleavage of such bonds much more difficult."

Several generations of chemists conducting research have collectively made significant progress in the direct transformation of inert aliphatic C–H bonds.

The new study presented by Guihua Chen and Zhangjie Shi summarizes effective strategies for advances in this area, with some representative examples.

Compared to the well-developed arene/alkene C-H activation, the functionalization of inert aliphatic C–H bonds of alkyl groups is still under investigation.

In general, there are three methods for the functionalization of aliphatic C-H bonds: the radical process, carbene/nitrene insertion and transition-metal mediated/catalyzed reactions.

As a result of the development of petroleum chemistry and traditional organic transformations, the photo- and thermo-induced direct halogenation of aliphatic C–H bonds via radical pathways is well known. Unfortunately, this is not an ideal organic reaction and has not been widely used in organic synthesis because of its poor selectivity. Significant efforts have been made to overcome this problem. An improved radical process, the Hoffmann–Loffler–Freytag (HLF) reaction, is probably the best-known radical reaction for constructing C–N bonds in organic synthesis. It is usually used for the synthesis of nitrogen-containing cycles and has even been successfully used in natural product chemistry.

Other strategies include Fenton and Gif chemistry and cross-dehydrogenative coupling (CDC). Radical processes are still the most powerful strategy for functionalizing aliphatic C–H bonds. The development of new techniques and new systems will make such strategies more controllable and useful in the near future.

Carbene/nitrene insertion in aliphatic C–H bonds is another well-studied and reliable method for direct conversion of C–H to C–C and C–N bonds. Over the course of decades of progress, this is the most reliable and well-developed method for aliphatic C-H activation; even an asymmetric variant has developed well.

Transition-metal-mediated C–H cleavage and further stoichiometric and catalytic transformations represent another powerful method for direct C–H bond transformations. Because the formation of C–M intermediates is key to the reaction, the process is referred to as C–H activation rather than C–H transformation. In this strategy, oxidative addition, electrophilic substitution, σ-bond metathesis and transition-metal-promoted homolysis are the four major pathways.

Direct C(sp3)–H functionalization is undoubtedly one of the most challenging and promising areas of organic synthesis. Several successful and elegant strategies have been developed and used in organic synthesis. However, compared with traditional organic transformations, this area is still less well studied, and much research is still needed.

More reliable, cheaper and more efficient processes for potential applications are needed. The development of efficient asymmetric catalytic systems is also challenging.

Developing new strategies for functionalizing independent aliphatic C–H bonds will present many challenges and opportunities for chemists. The collective efforts of several generations of chemists will lead to exciting developments, making organic synthesis greener and more environmentally benign.


This research received funding from the National Basic Research Program of China (2009CB825300) and the National Natural Science Foundation of China (21332001).

The National Science Review is the first comprehensive scholarly journal released in English in China that is aimed at linking the country's rapidly advancing community of scientists with the global frontiers of science and technology. The journal also aims to shine a worldwide spotlight on scientific research advances across China.

See the article:
Guihua Chen and Zhang-Jie Shi
Privileged strategies for direct transformations of inert aliphatic C–H bonds
Natl Sci Rev (June 2014) 1 (2): 172-175

[Attachments] See images for this press release:
Privileged strategies for direct transformations of inert aliphatic carbon-hydrogen bonds


Neutron tomography technique reveals phase fractions of crystalline materials in 3-dimensions

Neutron tomography technique reveals phase fractions of crystalline materials in 3-dimensions
The method overcomes limitations of existing techniques which are limited to the surface or small-sized specimens, and allows a 3-D representation of the phase fractions within the sample volume. The work has just been published in the journal "Advanced Materials". "For many engineering applications it is of major importance to characterize the bulk of materials spatially, instead of only probing selected locations. The new method provides exactly that capability, and the HZB-UTK team has demonstrated it by using samples made from stainless steel that undergo a phase ...

Vision-correcting electronic displays could let users dispense with glasses

Researchers at the MIT Media Laboratory and the University of California at Berkeley have developed a new display technology that automatically corrects for vision defects — no glasses (or contact lenses) required. The technique could lead to dashboard-mounted GPS displays that farsighted drivers can consult without putting their glasses on, or electronic readers that eliminate the need for reading glasses, among other applications. "The first spectacles were invented in the 13th century," says Gordon Wetzstein, a research scientist at the Media Lab and one of the display's ...

Vacuum treatment may limit damage after traumatic brain injury

July 31, 2014 – Controlled application of vacuum pressure is a promising approach to limiting tissue damage after traumatic brain injury (TBI), suggests an experimental study in the August issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health. "Mechanical tissue resuscitation"—consisting of vacuum pressure applied over the injured area of the brain—shows promise as a safe and effective treatment for TBI, according to the research report by Dr. Louis ...

UT Dallas study reveals effect of loud noises on brain

UT Dallas study reveals effect of loud noises on brain
Prolonged exposure to loud noise alters how the brain processes speech, potentially increasing the difficulty in distinguishing speech sounds, according to neuroscientists at The University of Texas at Dallas. In a paper published this week in Ear and Hearing, researchers demonstrated for the first time how noise-induced hearing loss affects the brain's recognition of speech sounds. Noise-induced hearing loss (NIHL) reaches all corners of the population, affecting an estimated 15 percent of Americans between the ages of 20 and 69, according to the National Institute ...

Monoamine oxidase A: Biomarker for postpartum depression

Monoamine oxidase A: Biomarker for postpartum depression
This news release is available in German. Many women suffer from baby blues after giving birth. Some even develop full-blown postpartum depression in the weeks that follow. Monoamine oxidase A, an enzyme responsible for the breakdown of neurotransmitters like dopamine and serotonin, plays an important role in this condition. In comparison to healthy women, women who experience postpartum depression present strongly elevated levels of the enzyme in their brains. This was discovered by a Canadian-German research team including Julia Sacher from the Max Planck Institute ...

Research reveals pervasive implicit hierarchies for race, religion, and age

As much as social equality is advocated in the United States, a new study suggests that besides evaluating their own race and religion most favorably, people share implicit hierarchies for racial, religious, and age groups that may be different from their conscious, explicit attitudes and values. The study findings appear in Psychological Science, a journal of the Association for Psychological Science. "People from relatively low-status groups can readily report that their group does not have the most power. At the same time, most groups, even if they have less social ...

Key to aging immune system is discovered

Key to aging immune system is discovered
There's a good reason people over 60 are not donor candidates for bone marrow transplantation. The immune system ages and weakens with time, making the elderly prone to life-threatening infection and other maladies, and a UC San Francisco research team now has discovered a reason why. "We have found the cellular mechanism responsible for the inability of blood-forming cells to maintain blood production over time in an old organism, and have identified molecular defects that could be restored for rejuvenation therapies," said Emmanuelle Passegué, PhD, a professor of medicine ...

Researchers at SGH and Duke-NUS a step closer to finding treatment for dengue fever

There have been several news reports that the world's first dengue vaccine will be available next year. However, the latest clinical trials show that the vaccine only provides a protection of around 50 per cent for DENV-2 and DENV-1, which are commonly found in Singapore. DENV-1 accounts for 90 per cent of infections locally as a large population lacks the immunity against this particular dengue virus serotype. Until a vaccine that can offer higher protection becomes available, it is crucial to find a suitable treatment for dengue fever, as there is presently none available ...

Senescence in adipose-derived stem cells and its implications in nerve regeneration

Senescence in adipose-derived stem cells and its implications in nerve regeneration
Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-derived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events (e.g., DNA damage) ...

A new way to generate insulin-producing cells in Type 1 diabetes

A new way to generate insulin-producing cells in Type 1 diabetes
VIDEO: Researchers discover a simple peptide that can induce new beta-cell formation in the pancreas. The findings show promise for a new approach to treating Type 1 diabetes. Click here for more information. La Jolla, Calif., July 31, 2014 -- A new study by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) has found that a peptide called caerulein can convert existing cells in the pancreas into those cells destroyed in type 1 diabetes-insulin-producing ...


Scientists model 'true prevalence' of COVID-19 throughout pandemic

New breakthrough to help immune systems in the fight against cancer

Through the thin-film glass, researchers spot a new liquid phase

Administering opioids to pregnant mice alters behavior and gene expression in offspring

Brain's 'memory center' needed to recognize image sequences but not single sights

Safety of second dose of mRNA COVID-19 vaccines after first-dose allergic reactions

Changes in disparities in access to care, health after Medicare eligibility

Use of high-risk medications among lonely older adults

65+ and lonely? Don't talk to your doctor about another prescription

Exosome formulation developed to deliver antibodies for choroidal neovascularization therapy

Second COVID-19 mRNA vaccine dose found safe following allergic reactions to first dose

Plant root-associated bacteria preferentially colonize their native host-plant roots

Rare inherited variants in previously unsuspected genes may confer significant risk for autism

International experts call for a unified public health response to NAFLD and NASH epidemic

International collaboration of scientists rewrite the rulebook of flowering plant genetics

Improving air quality reduces dementia risk, multiple studies suggest

Misplaced trust: When trust in science fosters pseudoscience

Two types of blood pressure meds prevent heart events equally, but side effects differ

New statement provides path to include ethnicity, ancestry, race in genomic research

Among effective antihypertensive drugs, less popular choice is slightly safer

Juicy past of favorite Okinawan fruit revealed

Anticipate a resurgence of respiratory viruses in young children

Anxiety, depression, burnout rising as college students prepare to return to campus

Goal-setting and positive parent-child relationships reduce risk of youth vaping

New research identifies cancer types with little survival improvements in adolescents and young adul

Oncotarget: Replication-stress sensitivity in breast cancer cells

Oncotarget: TERT and its binding protein: overexpression of GABPA/B in gliomas

Development of a novel technology to check body temperature with smartphone camera

The mechanics of puncture finally explained

Extreme heat, dry summers main cause of tree death in Colorado's subalpine forests

[] Privileged strategies for direct transformations of inert aliphatic carbon-hydrogen bonds