TADA reaction

29 December 2008 - reaction types

What: The TADA reaction or transannular Diels-Alder reaction.
Not to be confused with : the TA-DA reaction used to accompany or draw attention to a dramatic entrance or announcement'
Why: Big advantage: quick access to complex hydrocarbon skeletons for example steroids and other complex biomolecules. Big disadvantages: the macrocycles are floppy so you tend to end up with closely similar isomers. Use substituents at proper places to force favorable conformation. Macrocycles themselves present a challenge. A cis, trans, cis triene is required for DA lineup.

How: The first to try this reaction progressing from rearrangement reactions of cyclic dienes, was Dauben in 1981 (DOI). The C11 triene first rearranges in a sigmatropic 1,5-H shift which is then followed by the DA reaction forming trans-tricyclo(

Deslongchamps in 1987 extended the scope as a synthetic strategy by first examining a cis, trans,trans triene which forms a mixture of three isomers (DOI) before settling on a related trans, cis, cis one ( DOI).

Takahashi et al. in 1988 were the first to apply the methodology in steroid synthesis(DOI):

Most recently the reaction was used in total synthesis (Hayashi et al. 2008 DOI):

Hybrid hybrid car

28 December 2008 - News

We are familiar with hybrid cars that use both hydrocarbon fuel and a battery or a fuel cell for propulsion. But why not have one with a hybrid fuel cell system as well? A group of researchers from Queen's University explain how (Wechsler et al. 2008 DOI).

They first observe that the current contenders in fuel cells based on hydrogen storage either react in a exothermic reaction e.g. boron hydrides and metal hydrides or in a endothermic reaction e.g. cycloalkanes and piperidines (at the expense of fuel cell efficiency) and then propose that in a hybrid system heat generated by one reaction can be used to drive the other one. The symbiosis does not end there: the exotherms are generally solids but can be dissolved in liquid and pump-able endotherms.

In one demonstration endothermically reacting indoline is mixed with the exothermically reacting dimethylamine.borane (think ammonia borane) and water mixture with as catalyst palladium on carbon: both reactions go to completion without a nett enthalpic change. The calculated hydrogen storage capacity is 2.5%. The researchers are honest about the limitations of the system: the borate formed in the reaction is not soluble and the rates of both reactions are dissimilar.

Tetraalkyl nickel

27 December 2008 - News

Breaking news from the field of organonickel chemistry: a stable tetraalkyl nickel compound as reported recently by a Columbia University team (Carnes et al. DOI). The highly strained dibenzocyclooctatetraene 1 with one trans alkene bond is reacted with bis(cyclooctadiene)nickel(0) (after replacing one cod ligand with a tri(tert-butyl)phosphine ligand for added stability) with some surprising results.

In the initial reaction product 2 nickel forms a metallacyclopropane group exclusively with the trans alkene bond. Heating this compound in benzene at 60 °C forms the trans, trans, trans cyclobutane compound 3 possibly through reductive elimination of spiro nickelaspirocyclononane 4. Indeed this compound can be isolated as air-table crystals (stable without decomposition up to 290 °C) using 1 in excess. The molecule owes its stability to steric shielding of the nickel center.

Matthew Carnes, Daniela Buccella, Judy Y.-C. Chen, Arthur P. Ramirez, Nicholas J. Turro, Colin Nuckolls, Michael Steigerwald (2009). A Stable Tetraalkyl Complex of Nickel(IV) Angewandte Chemie International Edition, 48 (2), 290-294 DOI: 10.1002/anie.200804435

SOMO catalysis

22 December 2008 - Concepts

SOMO catalysis. Introduced by W.C. MacMillan in 2007 as an extension of two other concepts in chiral amine based organocatalysis : HOMO activation involving 4 pi electrons in enamine catalysis (increased HOMO energy activates a reaction) and LUMO activation with 2 pi electrons of iminium ions (decreased LUMO energy activates reaction). In SOMO activation a radical cation with an activated SOMO molecular orbital is formed by one-electron reduction of an enamine complex.

In a first report an aldehyde reacts enantioselectively with an allyltrimethylsilane as SOMO nucleophile (or somophile) in presence of a second-generation MacMillan organocatalyst and oxidizing reagent CAN (Beeson et al. DOI)

A reaction with a cyclopropane radical clock demonstrates that the intermediate truly is a radical because the ring opens along bond a forming a stable benzyl radical and not along bond b where a stabilized oxonium ion would expose a cationic intermediate.

In a recent extension a vinyl potassium trifluoroborate salt was thrown in resulting in a alpha vinyl aldehyde (Kim et al. 2008 DOI) although this blog struggles to understand the dicationic intermediate and the discrete molecule of BF3K expelled for this reaction to work, at least according to the investigators on duty.

Styrene is also found to react with aldehydes in this methodology with the intermediate radical neutralized (after another one-electron reduction to the carbocation ion) by a nitrite ion (Graham et al. DOI).

Reactions of enamine radical cations (as a reactant, not as a catalyst) were first described by Narasaka et al. in 1992 (DOI):

The SOMO organocatalysis concept has not yet attracted support from other research groups other than that of MacMillan himself except perhaps that of the Grimme group as evidenced by a recent 2008 report on aldehyde oxidation in a NHC / TEMPO combo (Quin et al. DOI):

with this fancy mechanism:

BKchem 0.125

19 December 2008 - software

The molecular editor BKchem is celebrating version 0.125 and all images you see on this website have been created using this tool. Most importantly it generates .svg images and secondly its free! (also see earlier post here). (Windows users make sure the export is stored as a SVG (Cairo))

Nice features are the way the software draws arrows and the way the software handles charges. Things still to work out are better fine tuning of moving a molecule versus moving an atom within a molecule. On the wish list: more orbital features, SVG import. Image above critical gold catalysed propagyl Claisen rearrangement in the synthesis of azadirachtin by Ley et al. (al 46 of them) in 2008 (DOI) is the first image generated with version 0.125. Through difficulties to the heights!

Azadirachtin.svg beschikbaar als download

Novelty iron magnetic nanorings

15 december 2008 - News

Chemists from 8 different chemical institutions have joined forces to bring you this new recipe for magnetic nanorings (Jia et al. 2008 DOI). Dimensions: height 80 -120 nanometer , outer diameter 150 nm and inner diameter 70 nm and each one made out of a single-crystal piece of iron oxide. As often in this brand of nanotechnology you can do the chemistry in the kitchen sink. Chemical analysis on the other hand takes a battery of rather expensive equipment.

Ferric chloride together with bits of sodium dihydrogen phosphate and sodium sulphate are dissolved in water and placed in an autoclave at 220 °C. A hydrothermal process forms hematite (alpha-Fe2O3) with correct nanoring morphology. The interplay of ions determine the morphology. Whereas the phosphate ions facilitate anisotropic crystal growth and promote the formation of tubes, the sulphate ions facilitate growth around the faces of the dodecasonal prism building blocks. The acidity increases as the reaction progresses and dissolution of Fe2O3 starts at the core eventually creating the nanoring hole. Residence time in the autoclave is important, eventually the hole in the ring will disappear again.

In two more steps hematite is converted to magnetite by high temperature reduction and then to ferrimagnetic maghemite in an oxidation process. Electron holography shows that the magnetic field lines form circles (the lines do not venture outside of the rings) and that is exactly what you need for magnetic data storage where the clockwise and counterclockwise magnetic fields represent the 1 and 0 states.

Benzophenone ketyl isolated

11 December 2008 - News

The benzophenone ketyl radical is well known for its deep-blue color when dissolved in organic solvents such as THF or toluene. These solvents are routinely dried in laboratories by continuous distillation with added amounts of of two components: benzophenone and sodium metal. They react to the ketyl which in turn reacts with any water thus drying the solvent. As long as the solvent does not turn blue it still contains water and the chemist has another cup of coffee.

For some incomprehensible reason no one has ever tried to isolate the ketyl compound (first observed in 1891 DOI) from this solution, that is until now! After no doubt tinkering a lot with the exact solvent composition (a mixture of diethyl ether and THF) and waiting patiently, Scott et al. (2008 DOI) were able to drag out crystals of K(Ph2CO) which were then analysed by x-ray crystallography. Main feature: a K4O4 cubane cage central core.

The discoverers are confident they can market solid K(Ph2CO) as a new chemical reagent.

Thomas A. Scott, Betty A. Ooro, David J. Collins, Michael Shatruk, Andrey Yakovenko, Kim R. Dunbar, Hong-Cai Zhou (2009). After 118 years, the isolation of two common radical anion reductants as simple, stable solids Chemical Communications (1) DOI: 10.1039/b815272a


5 December 2008 - Synthetic methods

What: Dehydrocoupling is the formation of a new main group metal-metal chemical bond with formation of hydrogen gas from a hydride with a suitable catalyst (recent review DOI). A type of dehydrogenation. First observed in dimerization of pentaborane by action of Platinum(II) bromide (Corcoran & Sneddon 1984 DOI). First silicon bond formation with (Aitken et al 1985 DOI) polymerization of phenylsilane in presence of the Petasis reagent to polyphenylsilane (DP around 10).

In a similar way polystannanes of the type (RR'Sn)n can be formed (Tilley et al. 1995 DOI).

Reaction of phenylphosphine with organozirconium catalyst Cp*2ZrCl2 and KH gives the cyclic pentamer (Stephan et al. 1995 DOI).
Mechanism: a sigma bond metathesis reaction mechanism is postulated for the polysilane formation reaction.

Also known as: dehydrogenative coupling - dehydropolymerization
Preceded by: Wurtz-Fittig reaction , coupling of elements through the halide and not the hydride. Disadvantages : use of expensive halides, handling of alkali metals.
Scope: One particular dehydrocoupling is in vogue as hydrogen storage solution: the reaction of amino borane (Denney et al. 2006 DOI) with an organoiridium pincer catalyst to an cyclic aminoborane oligomer with quantitative formation of hydrogen.
Most recently in 2008 using the same catalyst a practical synthesis was reported for linear high molar mass poly(N-methylaminoborane) (NHMeBH2)n (Staubitz et al. DOI).