Noteworthy Chemistry

October 8, 2012

Aggregates of thiazole–boron complexes emit light efficiently. Boron dipyrromethene (BODIPY) dyes are well-known examples of fluorophores that contain organoboron complexes. Their solutions fluoresce efficiently and exhibit sharp spectra and high photostability. Their Stokes shifts, however, are normally small; and their light emission is commonly quenched by aggregation.

Y. Kubota, M. Matsui, and co-workers at Gifu University (Japan) synthesized a series of thiazole–boron complexes that contain β-ketoiminate ligands. In contrast to BODIPY dyes, these complexes’ emission is enhanced by aggregate formation.

Compound 1 is an example of the authors’ thiazole–boron complexes. Hexane solutions of 1 are almost nonfluorescent; they have a fluorescence quantum yield (Φf) as low as <0.01. The fluorogen becomes emissive in the aggregated or solid state, an example of aggregation-induced emission enhancement (AIEE).

The Φf value of 1 in solution increases with increasing solvent viscosity or decreasing solution temperature, indicating that the main cause of the AIEE effect is the slowing of the rotation of the intramolecular phenyl group. Because intramolecular rotation is restricted in the aggregates, solid 1 is highly fluorescent in the solid state. (Org. Lett. 2012, 14, 4682–4685; Ben Zhong Tang)

Use a lab reactor to predict scale-up behavior. Projecting heat flow and temperature profiles for scaling up organic reactions typically requires mathematical modeling, reaction calorimetry, or both. E. M. Davis* and S. K. Viswanath at Eli Lilly (Indianapolis) report another option. Although the required lab reactions can be run in a reaction calorimeter, the authors used a computer-controlled, physically well-characterized jacketed reactor that accurately measures reaction and jacket temperatures and reacts to rapid jacket set-point changes.

The authors’ method eliminates much of the compounded calculation error inherent in other methods because it allows the system to calculate reaction temperature accurately by restricting heat flow across the jacket to the scaled-down equivalent of a large-scale vessel. The authors demonstrated the validity of their method by performing a first-principles derivation and four case studies. (Org. Process Res. Dev. 2012, 16, 1360–1370; Will Watson)

A chemoenzymatic step improves (S)-rivastigmine synthesis. (S)-Rivastigmine (1) is a cholinesterase inhibitor that shows activity in patients in the early stages of Alzheimer’s and Parkinson’s diseases. Current syntheses of this compound involve racemate resolution, asymmetric addition of organozinc species, or lipase-catalyzed kinetic resolution. To avoid these procedures, K. Faber and co-workers at the University of Graz (Austria) developed a synthesis of rivastigmine that includes an asymmetric enzymatic transamination.

The authors screened several transaminases (TAs) to catalyze the asymmetric transformation of a ketone into an amine. An ω-TA isolated from the bacterium Paracoccus denitrificans gave the best conversion and enantiomeric selectivity. The mechanism is shown in the upper part of the figure. The pyruvate coproduct was reduced to lactate by using lactate dehydrogenase in the presence of glucose dehydrogenase (GDH), glucose, and nicotinamide adenine dinucleotide (NADH).

As summarized at the bottom of the figure, the synthetic route to (S)-rivastigmine begins with carbamate formation, followed by the key asymmetric transamination step and amine dimethylation. This process does not use protecting groups and produces the target molecule in 66% overall yield and 99% ee. (Tetrahedron 2012, 68, 7691–7694; JosÉ C. Barros)

Magnesium(I) species shed light on Grignard reagent formation. It has been more than a century since V. Grignard discovered organomagnesium halides, now known as Grignard reagents. The process that forms Grignard reagents, however, is not fully understood. Mg(I) species are believed to be the key intermediates during the reagents’ formation, but this has not been confirmed experimentally. H. Schnöckel and coauthors at the Karlsruhe Institute of Technology (Germany), the Nikolaev Institute of Inorganic Chemistry (Novosibirsk, Russia)m and the Gdańsk University of Technology (Poland) generated and trapped MgBr species at high temperatures.

In pursuit of Mg(I) species, the authors attempted to reduce donor-free oligomeric anionic Grignard compounds; however, the reduction yielded only elemental magnesium. They switched to synthesizing MgBr from MgB2 and HBr at high temperatures by using a cocondensation graphite reactor. MgBr2 and MgB4 were generated first, and a subsequent reaction between gaseous MgBr2 and solid MgB4 yielded gaseous MgBr. The MgBr and excess MgBr2 were trapped in toluene to form a metastable solution in the presence of an electron donor (NEt3 or PEt3).

Highly reactive MgBr spontaneously disproportionates to give a magnesium mirror at above −40 °C. The authors indirectly confirmed the existence of radical MgBr by replacing bromide with the t-BuS anion because [(t-BuMgS-t-Bu)n] crystals are produced by the redox reaction between t-BuS and Mg(I).

Density functional theory calculations verified the relative reactivity of the compounds and intermediates involved. On the basis of their experimental observations, the authors propose a two-step single electron-transfer (SET) process for forming Grignard reagents (see figure). (Angew. Chem., Int. Ed. 2012, 51, 9025−9029; Xin Su)

Control the shape and size of functionalized silicon nanocubes in the solid state. J. G. C. Veinot and coauthors at the University of Alberta and the NRC-National Institute for Nanotechnology (both in Edmonton) developed a simple solid-state strategy to produce alkyl-functionalized silicon nanocubes with ≈8–15-nm edge lengths. Using a hydrogen silsesquioxane precursor, they formed oxide-embedded silicon nanocubes in a reducing environment. They then thermally annealed the nanocubes to tune their shape and uniformity.

The authors stress that time and temperature are key parameters for cube formation and growth. For example, processing at 1100 °C yields ≈2.9-nm pseudospherical silicon after 1 h, but the size increases to ≈7.6 nm after 24 h. Increasing the temperature to 1300 °C and annealing for 20 h produces ≈70% silicon nanocubes with a diamond lattice structure. The authors believe that this is the result of surface-energy minimization and temperature-assisted particle diffusion. Annealing for >20 h degrades particle uniformity and shape.

The orange-brown nanocubes were mechanically ground and etched with a 1:1:1 HF/EtOH/H2O solution to liberate hydride-terminated silicon cubes and large silicon pieces. The freestanding particles were passivated with dodecene via thermal hydrosilylation, purified by centrifugation, and redispersed in toluene. Large agglomerates and unfunctionalized particles were filtered to yield a nonopalescent yellow solution. IR spectroscopy indicated that the surfaces of the nanocubes are functionalized with dodecyl groups (J. Am. Chem. Soc. 2012, 134, 13958–13961; LaShanda Korley)

Copper and nickel catalysts make different pyrroles. The pharmaceutical industry is increasing the use of 2,4- and 3,4-diarylpyrrole building blocks for synthesizing active ingredients. Preparing the pyrroles is difficult, however, and requires harsh conditions, especially when the aryl substituents differ from each other.

N. Jiao and coauthors at Peking University (Beijing) and East China Normal University (Shanghai) developed a metal-catalyzed cyclization of α-azidoalkenes and aldehydes to form pyrroles. Using α-azidostyrene and MeCHO as starting materials, they screened various catalysts and reaction conditions. When they used a Cu(OAc)2 catalyst, they obtained the 2,4-substituted pyrrole exclusively .With NiCl2, the 3,4-substituted pyrrole was the only product.

After optimizing the reaction conditions, the authors used the catalysts to synthesize a range of 2,4-diarylpyrroles (1) and 3,4-diarylpyrroles (2) in moderate-to-good yields. The reactions are efficient, highly regioselective ways to obtain specific diarylpyrroles. They may provide access to new classes of biologically active compounds. (Org. Lett. 2012, 14, 4926–4929; Chaya Pooput)

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