All-carbon quaternary stereogenic centers in acyclic systems. A team of researchers led by Ilan Marek, professor at the Technion–Israel Institute of Technology in Haifa, described their
work in forming all-carbon quaternary stereogenic centers in acyclic systems from alkynes (3). Construction of chiral all-carbon
quaternary centers had been limited in previous aldol-based methodologies, according to a Nov. 28, 2012, Technion–Israel Institute
of Technology press release. The researchers used a single-pot operation, starting from classical hydrocarbons, to form aldol
products containing the desired all-carbon quaternary stereocenter through the concomitant formation of three new bonds, according
to the release. A challenge in forming the all-carbon quaternary stereocenters in acyclic systems had been the preparation
of all-carbon quaternary stereocenters in aldol adducts (3). The main problem that limits the formation of these stereocenters
is the absence of an efficient method of preparing stereodefined trisubstituted enolates in acyclic systems. The researchers
developed a different approach that involves the formation of two new stereogenic centers, including the all-carbon quaternary
one, through a combined carbometalation–oxidation reaction of an organocuprate to give a stereodefined trisubstituted enolate
(3). The researchers used this method to generate a series of aldol and Mannich products from ynamides. For his work in organic
synthesis, Marek received the Royal Society Chemistry Organometallic Award in 2011 and the Janssen Pharmaceutica Prize for
Creativity in Organic Synthesis in 2012.
Asymmetric carbon–hydrogen functionalization. Researchers at the Ecole Polytechnic Fédérale de Lausanne, School of Basic Sciences, Institute of Chemical Sciences and
Engineering, Laboratory of Asymmetric Catalysis and Synthesis, in Lausanne, Switzerland, recently reported on the development
of chiral cyclopentadienyl ligands as stereocontrolling elements in asymmetric carbon–hydrogen functionalization. The researchers
sought to tackle a limitation in the application of metal complexes coordinated by a single cyclopentadienyl ligand as a catalyst
in asymmetric reactions (4). The difficulty, they reported, has been designing cyclopentadienyl substituents that bias the
coordination sphere. The researchers developed a class of C2-symmetric cyclopentadienyl derivatives that control the spatial arrangement of the transiently coordinated reactants around
the central metal atom by developing rhodium (III) complexes with these ligands as highly enantioselective catalysts for directed
carbon–hydrogen bond functionalizations of hydroxamic acid derivatives (4).
Scale-up of artemisinin
A cost-effective, large-scale synthesis for the natural product artemisinin, an antimalarial treatment, has been elusive,
but researchers at the Indiana University (IU) developed a new approach that is moving toward that goal. The World Health
Organization has set a target-per-gram cost for artemisinin of 25 cents or less, but the current cost is about $2.40 per gram,
according to a Sept. 12, 2012, IU press release. "In 2005, the WHO claimed that the structure of artemisinin was too complex
for cost-effective synthesis," said IU Bloomington College of Arts and Sciences chemistry professor Silas Cook, in the IU
release.
Silas and other IU researchers' cost-effective approach to artemisinin uses cyclohexenone as a key starting material and basis
for developing reaction cascades in producing artemisinin in a five-pot sequence on a gram
scale (5). "The key to the ultimate success of synthetic artemisinin will be the large-scale production of the drug," Cook
said in the IU release. "As such, we had to completely rethink what qualified as suitable starting materials for this synthesis
and invent new chemistry." The next challenge will be to move from gram-scale to kilogram-scale production.
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