Carbon dioxide fixation latest

25 January 2010 - Organic chemistry

In the continuing coverage of chemical carbon dioxide fixation coverage (see earlier episode here) three recent contributions from Spain, The Netherlands and Japan. Sanz et al. (DOI) have been exploring catalytic reduction of carbon dioxide with hydrogen (60 atm) and a base (KOH/water) to the formate ion. Key is adding a NHC ligand as strong electron donor to iridium catalyst Cp*Cl2Ir. Using isopropanol instead of hydrogen in transfer hydrogenation also works with an turnover number of 150. As an added bonus the formic acid/formate system is also in the picture as an hydrogen storage vehicle. This probably means getting a research grant is twice as easy.

Angamuthu et al. (DOI) have not formate but oxalate on their mind as a form of fixated carbon dioxide. Their catalyst is based on Copper(II) acetylacetonate with copper(II) reduced to copper(I) with addition of an thiol (forms a disulfide) containing ligand. Unexpectedly this compound was found to be oxidized by carbon dioxide and not by oxygen. A system was then devised with spent copper(II) reduced back electrochemically which process turned out to be more favorably than direct CO2 reduction

Minakata et al. (DOI) too claim to have found a new way to capture carbon dioxide before it can destroy our climate. They exploit an old reaction reaction in a novel way: carbon dioxide is known to react with simple alcohols (for example allyl alcohol ) to form an alkyl carbonic acid but the chemical equilibrium is unfavorable. Solution: the unstable carbonic acid RO(CO)OH is iodinated with sodium hypoiodite to RO(CO)OI which then reacts in a kind of halolactonization to an organic carbonate.
But where formate and oxalate salts have some utility in their own right it is difficult to see genuine bulk applications for the particular cyclic carbonate formed. In this respect the Japanese seem to have lost the plot.

Power on main-group elements

21 January 2010 - Chemical bonding

Philip Power offers a new insight into the chemistry of some of the heavier main group elements - that square in the periodic table cornered by aluminium and tellurium - in a recent review in Nature (DOI). In it he proposes that based on the type of bonding and reactivity compounds containing elements in this square can really behave as transition metals.

Power starts his investigation with the chemistry of some compounds containing two such heavier main group elements joined by a multiple bond such as mes2Si=Simes2. On going down a group (Si > Ge > Sn > Pb) the M-M multiple bond bond length increases and instead of having a sigma bond and one or more pi bonds al that remains is a M-M single bond with an nonbonded electron pair (donor) on one metal center leaving the other center electron-deficient with a positive charge. Some of these compounds break up in some kind of Wanzlick equilibrium to form the corresponding carbenes which also have acceptor and donor sites.
Thus armed with occupied and empty frontier orbitals these compounds display reactivity not unlike that of transition metals for example with small molecules such as hydrogen and ethylene. The compound ArGe:::GeAr reacts with hydrogen in oxidative addition (ordinarily the preserve of transition metals) owing to electron donation of the occupied hydrogen sigma bond into the symmetrical GeGe LUMO on the one hand and back donation of the GeGe pi bond into the antibonding hydrogen sigma bond. Carbenes and the heavier analogs also react with hydrogen and also occasionally with ammonia Frustrated Lewis pairs too owe their reactivity to favorable non-self extinguishing frontier orbitals. In addition many compounds in this cluster coordinate with alkenes just like transition metals in the Dewar-Chatt-Duncanson model.

Power in his review presents a strong case for main group element as transition elements which is also the title but is the theory entirely new? The isolobal principle proposed by Roald Hoffmann in 1976 at least also explains reactivity by looking at frontier orbitals only for example between that of the methyl (main group carbon) radical and manganese (transition metal) pentacarbonyl.
Power, P. (2010). Main-group elements as transition metals Nature, 463 (7278), 171-177 DOI: 10.1038/nature08634

Oseltamivir number 27

18 January 2010 - Organic Chemistry

Osato et al. (DOI) have signed on for Oseltamivir total synthesis number 27 (previous episode here) even though it is clear by now that the drug Tamiflu is totally ineffective against the dreaded swine flu. Nevertheless this particular synthesis has several interesting features notably its start from humble and widely available ribose 1. Reaction with pentanone and methanol gives mono-ol 2 and an Appel reaction (triphenylphosphine/iodine/imidazole) replaces the alcohol group with iodine in 3. The next step is a zinc initiated Bernet-Vasella reaction which opens up the ribose ring. The intermediate aldehyde 4 is not isolated but reacted with ethyl 2-(bromomethyl)acrylate 5 in a reformatski reaction to diene 6. Olefin metathesis is next accomplished with using a Grubbs-Hoveyda catalyst (2 mol% loading!) to cyclohexene 7, ketal cleavage proves difficult (poor selectivity) but AlCl3 in combination with Et3SiH save the day for 8. Another narrow escape presents itself when it is found to be possible to first add a mesylate group in 9 (MsCl, Et3N) and then a triflate group in 10 (Tf2O, pyr) on the two adjacent alcohol groups (keep temperature really low!). In the final section the triflate group is replaced by azide in 11 (NaN3, water/acetone), stauding reduction forms the amine and reaction in triethylamine forms the azirinidine 12 (total yield from ribose: 28%) which is only three known steps away from oseltamivir 12.

Osato, H., Jones, I., Chen, A., & Chai, C. (2010). Efficient Formal Synthesis of Oseltamivir Phosphate (Tamiflu) with Inexpensive -Ribose as the Starting Material Organic Letters, 12 (1), 60-63 DOI: 10.1021/ol9024716
Oseltamivir ribose route

Palau amine

08 January 2010 - Die Totaler Synthese

Palau'amine is a bisguanidine antobiotic first isolated from the marine sponge Stylotella agminata (western Caroline Islands part of Palau) in 1993 (Kinnel et al. DOI). Take 600 g of sponge, extract it with 6 liters of methanol, do multiple sessions of chromatography and you may end up with 14 mg of the compound. Palau'amine is characterized by a strained bicyclic 3.3.0 cyclooctane core, a large number of stereocenters, a sensitive pyrrole group and by two guanidine rings which in addition to the potential medicinal properties has made it a natural target for several total synthesis teams over the years. Synthetic palau'amine is now a reality thanks to Seiple and Su of the Baran group (DOI) and features several of Baran's hobby horses: biomimetic synthesis, cascade reactions and redox economy.

The final step is notable. In it (4 mg(!) scale) the azide groups in 1 are reduced to amine groups (hydrogen, palladium acetate) in 2 and an amide group is formed in 3 using EDC. A prolonged reaction with trifluoroacetic acid forms amidine tautomer 4 which opens the door for a transannular amine-imine addition reaction to palau'amine 5. Overall yield 0.0015% from commercial precursors. As a note of interest the final ring closing step according to the publication was envisioned based on an old-fashioned hand-held molecular model.

Seiple, I., Su, S., Young, I., Lewis, C., Yamaguchi, J., & Baran, P. (2009). Total Synthesis of Palau'amine Angewandte Chemie International Edition DOI: 10.1002/anie.200907112

PETN in the research laboratory

03 January 2010 - CSI Detroit

klik hier voor de afbeelding op ware grootteAnd speaking of PETN, (see previous blog) a quick trip around the world for the latest on detection and forensics PETN research. First up is Mayhew et al. (DOI) who showcase a novel proton transfer reaction Time-of-flight mass spectrometer manufactured by Austrian company Ionicon (website). The detection of a range of explosives from the headspace of the room temperature solids was demonstrated despite their very low vapour pressure, for example that of PETN is stated as 3.8x10-6 Torr.
This particular detector is as big as a freezer but the next one can fit in a shoe. Babis et al. (DOI) in collaboration with Sandia National Laboratories have built a hand-held ion mobility spectrometer (IMS) for explosives detection. In ISM a molecule is (usually radioactively) ionized and then forced to travel through a so-called drift tube with an applied electric field and an opposing carrier gas. The ions mass, shape and charge then determine how long it will take to reach the end of the tube. One would expect to find one peak in the ion mobility spectrum for each type of explosive but for some unexplained reason PETN has multiple peaks that should complicate analysis. In any case the vapor concentration of PETN at the detection limit was found to be 180 ppb.
No money to buy all this expensive equipment or does your country suffer from certain trade sanctions? Chaloosi et al. from the Iranian Tarbiat Moallem University report on a poor-man PETN detection system based on humble TLC (DOI). Well, the technique used was the more advanced high performance Thin layer chromatography and spot detection was aided by a densitometer all of which made it possible to determine a PETN detection limit of 0.180 microgram per spot.

More news from the forensics department. Ordinary gas chromatography was used for the detection of PETN by Oxley et al. of University of Rhode Island who in a recent study (DOI) examined traces of it on hair samples from students doing explosives field training at Fort A.P. Hill. 80% of these students tested positive on average with those with black hair among 7 different colors taking the lead (there is no limit to the amount of things you can test!).
And finally two studies from the journal Science and Justice on isotope analysis relating the isotopic signature if a PETN sample to the original manufacturing site. In French research Widory et al. (DOI) combined isotope ratio mass spectrometry and elemental analysis to discriminate between different PETN manufacturers and even went as far to analyse how isotopic signatures vary over time (and now for my next experiment I will be needing Yugoslavian TNT from the 1960's, the 1980's and 1990's!). In Australian research Benson et al. (DOI) carbon and nitrogen isotope values were used to identify PETN from various sources. Wikipedia is vague on the origin of geographic distribution of isotopes. It only explains how heavy oxygen is being depleted with latitude due to weather pattern but what about carbon or nitrogen?