Chemical Science Blog

Tetraazafulvalenes are super electron donors but they are elusive – only one has ever been isolated before. Scientists in the UK have managed to make a series of them by reacting imidazolium salts with their derived carbenes. They are very reactive but the mixture of precursor salt and base still produces the same powerful reductive chemistry that is the hallmark of tetraazafulvalenes.

Link to journal article
Imidazole-derived Carbenes and their Elusive Tetraazafulvalene Dimers
P I Jolly et al, Chem. Sci., 2012, DOI: 10.1039/c2sc20054f

Researchers from the University of California have used computational studies to uncover the mechanism of a key step in their synthesis of a powerful toxin.

Last year, Christopher Vanderwal’s group published a very elegant and efficient approach to strychnine (1), resulting in the shortest synthesis of this alkaloid to date. An intramolecular Diels–Alder reaction of a Zinke aldehyde (3) provided tetracyclic intermediate (2) as a single diastereoisomer.

Computational modelling, performed in collaboration with K. Houk’s group, provided evidence that stepwise anionic cycloadditions were operational as opposed to a concerted Diels–Alder reaction.

The presence of a potassium base was found to be essential for the stepwise Michael/Mannich cascade to occur. The potassium cation is thought to organise the aldehyde into the appropriate conformation for the initial Michael reaction to occur. Additionally, the formation of a stable potassium enolate is thought to be the driving force for the Mannich reaction. Subtle changes in the reaction conditions therefore influence the preference for the formation of 6 over cycloreversion to form 4.

The researchers are hopeful that these interesting findings will enable the application of related Diels–Alder reactions to a wider range of substrates.

Read Vanderwal’s Chemical Science Edge article >

For the first time, visible light mediated synthetic photochemistry has been applied in a continuous flow reactor, say scientists from Germany. Using an operationally simple photoreactor design, the team performed several Ru(bpy)₃²⁺-catalysed transformations with 10–50 fold rate enhancement over the corresponding batch methods.

Lower catalyst loadings were needed to produce the desired products in excellent yields within residence times between one and 30 minutes, while minimal waste products were formed, they claim. They add that the process is readily scalable and provides access to large quantities of product in relatively short time.

Reference:
Visible-light-mediated photochemistry: Accelerating Ru(bpy)₃²⁺-catalyzed reactions in continuous flow
F R Bou-Hamdan and P H Seeberger, Chem. Sci., 2012
DOI: 10.1039/c2sc01016j

Microwaves have been used to promote organic reactions since the 1980s and they can lead to higher yields and shorter reaction times than conventional heating, but why? Conventional wisdom says that it’s the heat that promotes the reactions, but new research shows that the waves could be interacting with the molecules directly.

Gregory Dudley and colleagues from Florida State University, Tallahassee, in the US, discovered a microwave effect occurring during a Friedel-Crafts benzylation reaction in a microwave. The microwave-absorbing polar reactant – a pyridinium – reacted in a non-polar and largely non-microwave-absorbing solvent – toluene. Previously, a non-polar reaction system had to be doped with ionic liquids, which converted the microwaves to heat. ‘Polar molecules interact more strongly with microwaves than non-polar molecules,’ explains Dudley. ‘So we tried to design a system in which only the reaction substrate would interact with the incident radiation energy.’

The team found that the microwave irradiation induces reactivity levels that can’t be duplicated by conventional heating, without reaching the temperature required in conventional heating. ‘It’s hard to speculate what exactly is going on,’ says Dudley. ‘Our focus was to identify an effect.’ Dudley adds that there is still much to learn about the differences between activating reactions with microwaves and conventional heating.

Defying conventional wisdom, new research shows it could be microwaves that promote microwave-assisted reactions, not heat

Read the full story in Chemistry World

Link to journal article
On the rational design of microwave-actuated organic reactions
Michael R. Rosana ,  Yuchuan Tao ,  Albert E. Stiegman and Gregory B. Dudley
Chem. Sci., 2012, Advance Article
DOI: 10.1039/C2SC01003H

There are very few examples of non-macromolecular gene carriers to take DNA through lipid membranes. Now, a remarkably small, trivalent, dipeptide-based gene carrier has been developed by scientists in Germany to bind to DNA to transport DNA into human cells.

The carrier consists of 6 amino acids and 3 guanidinocarbonyl pyrrole moieties; it carries 3–4 positive charges at physiological pH, which is unprecedented for non-viral gene carriers. Also, the carrier doesn’t require additional helper molecules, for example, phospholipids.

Reference:
Efficient Gene Delivery into Cells by a Surprisingly Small Three-Armed Peptide Ligand
H Y Kuchelmeister et al, Chem. Sci., 2012
DOI: 10.1039/c2sc01002j

US scientists have made multifunctional lactones – normally a challenging process – in an efficient way, under mild conditions and without protecting groups or by-products.

Multifunctional molecules are attractive for cellular targeting, imaging and drug delivery or as synthetic mimics of biological structure and function.

The team began with a symmetrical trifunctional molecule – benzotrifuranone – and sequentially functionalised its three reactive sites by aminolysis. The functional groups were designed in such a way that each functionalisation diminishes the reactivity of the remaining sites so that the groups only functionalise one reactive site each time.

Reference:
Molecular multifunctionalization via electronically coupled lactones
M B Baker, I Ghiviriga and R K Castellano, Chem. Sci., 2012
DOI: 10.1039/c2sc00943a

A new class of tunable molecular wires has been made by researchers in the US. The team has made new cyano-functionalised oligoenes and they report the longest oligoene crystal ever made.

Cyano groups decrease oligoenes’ band gaps and stabilise them for study under normal laboratory conditions while preserving the conjugation along the poly-olefin backbone. This particular class of oligoenes has not been studied much.

Functionalised oligoenes are ideal structures for nanoscale electronic and structural components and they could be used in photovoltaics because their band gaps are easy to tune and their absorptions cover the visible spectrum.

Reference:
Functionalizing Molecular Wires: A Tunable Class of α,ω-diphenyl- μ,ν-dicyano-oligoenes
J S Meisner et al, Chem. Sci., 2012
DOI: 10.1039/c2sc00770c

Researchers from Wuhan University and the Lanzhou Institute of Chemical Physics have described a sulfur-promoted cleavage of aryl–iodo bonds by a Pd(ll) species.

Aiwen Lei and co-workers showed that treatment of thioimido substrates (1) with a catalytic amount of a “pincer” Pd(ll) complex (2) at 80 ˚C could form thiazoles (3) in excellent yield.

In Nature, sulfur plays an important role in tuning the electronic properties of metals found in proteins. In analogy to the role of cysteine (a sulfur-containing amino acid), the incorporation of a donating sulfur ligand in the starting material (1) is thought to promote reaction of the Pd(ll) centre with the aryl-iodo bond. The reaction is thought to proceed via formation of complex A, whose structure has been confirmed by single crystal analysis.

Further investigations into the mechanism of this reaction are ongoing, but the researchers are hopeful that this work will enable new opportunities for the use of Pd(ll)–Pd(lV) chemistry, a powerful yet under-investigated catalysis mode.

Find out more by downloading Lei’s Edge article today.