Noteworthy Chemistry

April 9, 2012

Structural constraints help stabilize triarylboranes. Triarylboranes are useful building blocks for materials that have desirable optical or electronic properties, or both. The boron center of these boranes is both highly reactive and conventionally sterically protected. A. Wakamiya, S. Yamaguchi, and coauthors at Nagoya and Kyoto Universities (both in Japan) found a way to stabilize triarylboranes by using a structural constraint technique.

Inspired by the report of a synthetic protocol for constrained triphenylphosphines and triphenylarsines (Hellwinkel, D.; Wiel, A.; Sattler, G.; Nuber, B. Angew. Chem., Int. Ed. Engl. 1990, 29, 689–692), the authors treated bromoborane 1 with 2,6-di(2-propenyl)phenyllithium to produce the twofold intramolecular Friedel–Crafts cyclization precursor 2 in 80% yield. The cyclization of 2 proceeds in the presence of Lewis acid Sc(OTf)3 to give planar triarylborane 3 in 68% yield. CrO3 oxidization of 3, followed by methylation with Me2Zn, produces D3h-symmetrical 4 in 49% overall yield. Similarly, the researchers synthesized triarylborane derivative 5 with extended π-conjugation from a dibrominated substrate with the help of a fourfold intramolecular Freidel–Crafts cyclization.

The crystal structures of 4 and 5 clearly show almost perfect planar backbones. The B–Cipso bonds in 4 (1.519–1.520 Å) and 5 (1.520–1.532 Å) are much shorter than those of unconstrained triarylboranes. The authors believe that the shorter B–Cipso bonds are the result of p–π conjugation between the ipso carbon atoms and the boron atoms, which may cause more effective π-donation.

π-Donation is also responsible for the lower reactivity of 4 and 5 compared with normal arylboranes. Both compounds are stable in the presence of air and water, and purification by column chromatography does not decompose them. Borane 4 is even inert to very strong Lewis bases such as DBU (1,8-diazabicycloundec-7-ene) and DABCO (1,4-diazabicyclo[2.2.2]octane).

Compounds 4 and 5 retain some Lewis acidity. Both coordinate with fluoride ion, which converts their configurations from planar to bowl-shaped. Adding BF3Et2O to the fluoride complexes regenerates the neutral, planar forms of 4 and 5. (J. Am. Chem. Soc. 2012, 134, 4529–4532; Xin Su)


Make solvent-tunable gold nanoparticles. K. Niikura and fellow researchers at Hokkaido University (Sapporo, Japan) and JST-CREST (Tokyo) tackled the design of 20-nm diam amphiphilic gold nanoparticles (AuNPs) that can traverse an organic–aqueous interface but maintain their solubility in the aqueous phase. They used a short (600 Da) poly(ethylene glycol) (PEG) polymer with an n-octyl head and a thioalkyl tail as a surface ligand (1).

When the authors mixed the C8-PEG derivative or unmodified thioalkyl PEG (2) with octanethiol (3), they could tailor the flexibility of the inner PEG unit to alter its hydrophilicity in model self-assembled monolayer studies. They immobilized the modified polymers or free octanethiol on the AuNP surfaces via an exchange reaction with citric acid. They used UV absorption to monitor the dispersion (red) and aggregation (blue) of the functionalized AuNPs. AuNPs with 90% C8-head PEG and 10% octanethiol were soluble in water, MeOH, and CH2Cl2, whereas 100% C8-head–functionalized AuNPs aggregated in H2O and MeOH.

1H NMR studies confirmed the role of PEG-based conformation in the ligands’ dispersibility in organic and aqueous solvents. Reducing the size of the AuNP (i.e., increased ligand curvature) easily dispersed the 100% PEG head or 100% C8-PEG head in water because the inner PEG segment is hydrophilic. The conformational flexibility also allowed efficient transfer between phases because it decreased the nanoparticles’ surface energy. (Langmuir 2012, 28, 5503–5507; LaShanda Korley)


Use molecular gels as optical devices. Molecular gels are soft materials consisting of steric networks of low–molecular weight amphiphiles that immobilize large amounts of water or organic liquids. Researchers believe that the amphiphilic molecules automatically phase-separate before their chains are oriented. Entanglement of the chains forms a 3-D network that imbibes the liquid molecules. Until now, the gels have been used only in biomedical applications.

Researchers are now developing nonbiological molecular gel applications. For example, dry amphoteric sugar molecules can absorb oil droplets to form ordered gel structures in the presence of an oil–water mixture. Gels can also act as catalysts; researchers can place catalytic sites at strategic locations in the self-assembled network or in the liquid pool to promote organic reactions in either phase.

G. John and coauthors at the City College and Queens College of the City University of New York and Tulane University (New Orleans) describe molecular gels that can be used as “soft” optical devices. The amphiphilic molecules are mannitol derivatives with diol groups flanked by ketal structures. The molecules self-assemble via hydrogen bonding of the diols and hydrophobic interactions of the ketals. The flexible gels are transparent and can be used as magnifying lenses or light-refracting prisms. (Angew. Chem., Int. Ed. 2012, 51, 1760−1762; Sally Peng Li)


Integrate two domino sequences to make oxazoles. Researchers have devoted much effort to synthesizing oxazole derivatives. Oxazoles are useful building blocks for biologically relevant products and optical devices. A team at Central China Normal University (Wuhan) led by A.-X. Wu developed a method for preparing oxazole derivatives through convergent integration of two so-called self-labor domino sequences from different substrates, ketones and benzoins.

As an example, the authors prepared oxazole derivative 4,5-diphenyloxazol-2-yl phenyl ketone (1) in 73% isolated yield by using domino sequences from acetophenone and benzoin in a one-pot procedure. The authors believe that both reactants oxidize to α-dicarbonyls, which condense with ammonia and cyclize to form the oxazole ring.

The broad scope of substrates suitable for the method includes electron-rich and electron-poor aromatic and heteroaromatic methyl ketones and α,β-unsaturated methyl ketones. The method’s advantages are readily available starting materials, mild reaction conditions, metal-free catalysts, and simple operation. (Chem. Commun. 2012, 48, 3485–3487; Ben Zhong Tang)


An aldol cyclization selectively produces a drug intermediate. In a key stage in the synthesis of the pharmaceutical intermediate (1R,4R)-5-phenylbicyclo[2.2.2]oct-5-en-2-one, S. Abele and co-workers at Actelion Pharmaceuticals (Allschwil, Switzerland) cyclized 2-phenyl-2-{(R)-1,4-dioxaspiro[4.5]decan-7-yl}acetaldehyde under acidic conditions to give (1R,4R,5S,6S)-6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one. The reaction can generate four possible isomers, but in practice only three appear when the reaction medium is EtOAc–2 M HCl.

Isolating the isomers showed that one isomer is unproductive in the subsequent elimination step. The authors subjected each isomer to the optimized cyclization reaction conditions; the desired isomer is stable under these conditions, whereas the other two partially isomerize to the stable one. The researchers isolated (1R,4R,5S,6S)-6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one in high diastereomeric purity by filtering the reaction mixture. They obtained the final 51% yield of this isomer over two steps (oxidation to give the aldehyde followed by cyclization) with >99.5:0.5 er. (Org. Process Res. Dev. 2012, 16, 129–140; Will Watson)


Monitor enantiopurity of products made in ionic liquids on-line. Ionic liquids (ILs) are promising solvents for organic synthesis because their vapor pressure at ambient temperature is very low. But this property implies that reaction products formed in ILs must be extracted with organic solvents. In addition, there is a need for rapid on-line sampling methods coupled with chiral chromatography to monitor the enantiomeric purity of optically active compounds.

Q. Zhao, P. Twu, and J. Anderson* at the University of Toledo (OH) developed a sampling device that captures products in the headspace of the reaction flask by solid-phase microextraction (SPME). The products are thermally desorbed into a GC port. The authors tested three SPME coatings on the chiral compounds shown in the figure. The coatings were poly(dimethylsiloxane) (PDMS), polyacrylate, and a polymeric IL-based filter. PDMS had the highest extraction efficiency after 90 min.

The authors prepared calibration curves to demonstrate the method’s ability to quantify the products. The detection limits are lower than the concentration ranges usually encountered in organic synthesis. For compounds with hydroxyl groups, the authors devised an “on-fiber” derivatization procedure that uses acetic anhydride to esterify the hydroxyls in <10 s.

Researchers can use this method for determining the enantiomeric excess of products from reactions in ILs on-line. The authors point out that SPME fibers are inexpensive and can be used with any GC equipment. [The authors cite a US$300 price for SPME fiber but do not report the quantity.—Ed.] (Chirality 2012, 24, 201–208; JosÉ C. Barros)


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