N EWS O F T H E W E E K
CHIRAL ALCOHOLS SYNTHESIS: New method yields
enantiopure tertiary alcohols
M
Interior of a carbon nanotube.
I STOC K
AKING CHIRAL TERTIARY ALCOHOLS has always been a tricky endeavor. Now, a research group led by Varinder Aggarwal, a chemist at the University of Bristol, in England, reports a new strategy using boron-based reagents to produce them (Nature 2008, 456, 778). NOVEL ROUTE The work “is a superb piece of innovaBoron reagents direct which tive reaction engineering,” comments enantiomer is formed David MacMillan, who works on chiral synthesis at Princeton University. O Karl Hansen, the scientific director of chemical process R&D for Amgen, calls O N the strategy “striking” in an associated commentary. “Because a compound’s enantiomers often have different biological activities, this could be particularly Base useful for drug discovery and development,” Hansen notes. BR(OR´)2 BRR´2 Aggarwal’s team starts with relatively easy-to-make enantioenriched secondOH OH ary alcohols and converts the hydroxyl R R group into a carbamate group. Next, a base nips a hydrogen atom from the carbamate to form an intermediate anion. Then, a boron-based reagent reacts with
NANOTECH SAFETY RISK ASSESSMENT: NRC report blasts federal research strategy that addresses risks of nanomaterials
T
HE FEDERAL GOVERNMENT’S research plan for assessing the potential environmental, health, and safety (EHS) risks of nanomaterials is inadequate, concludes a new report from the National Research Council. The report emphasizes the need for a national strategic plan—one that includes a broader group of stakeholders and goes beyond what the federal multiagency National Nanotechnology Initiative can develop. “If we want to see a good return on the investment that is going into nanotech research and development, something else has to happen when it comes to risk research,” emphasizes Andrew Maynard, chief science adviser of the nonprofit Project on Emerging Nanotechnologies and a member of the NRC committee that reviewed the NNI plan. WWW.CEN-ONLI NE.ORG
8
the anion to provide an alkyl group. The carbamate group is expelled, and hydrogen peroxide added to the pot reintroduces the alcohol functionality. The step involving the boron reagent comes with “completely unexpected results,” Aggarwal says. As it turns out, the nature of the reagent—that is, whether it is a boronate ester or a borane—dictates which enantiomer is produced, with striking selectivity. “The first time we did the reaction, it was completely investigative, and we did not expect such enantiomeric purity,” Aggarwal says. His team reports making some two dozen tertiary alcohols this way, each with more than 90% enantiomeric selectivity. “The capacity to build either enantiomer of the product from the same starting material simply by changing the nature of the boronate species is unique and important,” MacMillan says. “This chemistry and the underlying concepts will be heavily utilized by the chemistry community.” Boron reagents “can act as sources of different alkyl groups,” Hansen notes. “This means that a diverse set of products can be made conveniently from a common starting material.” Patrick J. Walsh of the University of Pennsylvania calls the work “very clever and interesting.” But, he says, “Aggarwal’s three-step method would really need to be highly efficient to compete” with his and other groups’ strategies of single-step asymmetric additions to ketones using organozinc reagents and chiral titaniumbased catalysts. These methods, he explains, “have been performed with high levels of enantioselectivity, greater than 90%,” for similar compounds.—SARAH EVERTS
The NRC committee looked at several elements that it considered essential for a research strategy. “The government document fell short on every one of those elements,” Maynard notes. In particular, the committee found that the government’s strategy lacks a clear vision, specific goals, and an evaluation of the current state of the science, Maynard notes. Rep. Bart Gordon (D-Tenn.), chairman of the House Committee on Science & Technology, said in a statement that he will reintroduce NNI legislation next year. H.R. 5940, which passed the House in June (C&EN, June 23, page 26), contained several provisions “aimed at correcting weaknesses in the federal research program cited in the NRC report,” Gordon noted. A coalition of concerned stakeholders, including industry trade groups, nanomaterial manufacturers, and environmental organizations, reacted to the report by issuing a joint statement that echoes the concerns raised by the NRC committee. “The NRC report lends all the more urgency to our coalition’s call for the independent development of a comprehensive road map to guide federal research on the EHS implications of nanotechnology,” they wrote. NNI officials say member agencies are already pursuing a new, broader national strategy.—BRITT ERICKSON
DECEM B ER 15, 2008
