NEWS OF THE WEEK
CYCLIZATION SHORTCUT ORGANIC SYNTHESIS: Combined route to complex cyclic products saves steps, improves yields CATALYTIC dehydrogenation approach promises
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to streamline access to products of the ring-forming Diels-Alder reaction. The approach generates starting materials and enables them to be cyclized in a single process, reducing the number of steps and improving yields relative to the conventional two-stage process. The work was carried out by grad student Erik M. Stang and chemistry professor M. Christina White of the University of Illinois, Urbana-Champaign (J. Am. Chem. Soc., DOI: 10.1021/ja2059704). Until now, dehydrogenation and other C–H oxidation reactions have primarily been used to add functional groups to carbon frameworks, Stang and White point out in their paper. They instead use dehydrogenation to produce conjugated dienes and convert them into activated intermediates that participate, as they are formed, in Diels-Alder cyclization—a complexitygenerating reaction that combines dienes and electrondeficient olefins into cyclohexenes. The strategy skirts a common problem in conventional Diels-Alder chemistry: The necessary conjugated diene starting materials are often difficult to synthesize and isolate. Such dienes can be built via alkene dehydrogenations in which two adjacent C–H bonds are cleaved. But chemists rarely turn to dehydrogenation to create dienes because the reaction conditions cause dienes to oligomerize or react in other ways before they can be isolated, White says. Stang and White’s combined dehydrogenation/DielsAlder reaction converts terminal olefin starting materi-
als directly into complex Diels-Alder cycloaddition products, skipping separate diene synthesis and isolation. In the combined process, the terminal olefin undergoes palladium(II) sulfoxide-catalyzed dehydrogenation and isomerization to give a reactive trans-diene intermediate, which then undergoes Diels-Alder cycloaddition with an electron-deficient olefin to form a cyclohexene. The researchers used the dehydrogenation/Diels-Alder reaction to synthesize hydroisoindolines, cis-decalins, hydroisoquinolines, isoindoloquinolines, and other complex cyclic molecules of interest in natural product synthesis and medicinal chemistry. Their syntheses required fewer steps and produced UNIFIED PROCESS Combined higher yields than dehydrogenation/cyclization uses a palladium traditional routes catalyst to convert a terminal olefin to an activated do—in one case, diene (not shown) that reacts with an electronthree steps and 34% deficient olefin to form a cyclohexene product. yield, compared with six steps and R H Palladium 17% yield for the sulfoxide EWG EWG H catalyst conventional route. + R Chemistry proEWG EWG fessor Paul Wender H H of Stanford UniTerminal ElectronCyclohexene versity says Stang olefin deficient olefin product and White have deEWG = electron-withdrawing group veloped a new way to make dienes for use in Diels-Alder cycloadditions, “providing in one step an impressive increase in structural complexity and thus potential value.” He notes that this type of step-count reduction is a key way to reduce the cost, generated waste, and required time of a synthesis. Wender adds, “Achieving the combined process is notable because its reactants, reagents, intermediates, and products must be compatible and effective—a goal that can often be difficult to achieve, even with one reaction. I think the reaction has immediate practical value in both academia and industry.”—STU BORMAN
ECONOMY Despite tough times, chemical executives expect to invest Rising raw material costs and a struggling global economy aren’t deterring chemical industry executives from pursuing acquisitions, investing in new technology, and expanding into new markets. That’s the conclusion of a new survey by KPMG, an audit, tax, and advisory firm. In the survey of 142 senior-level chemical executives in the U.S., Europe, and Asia, 66% of respondents said their firms will engage in mergers and acquisitions (M&A) as the buyer in the next two years. European executives were even more bullish, with 71% expecting to be buyers.
In addition, 70% of chemical executives said their companies have cash on their balance sheets they can use for deal-making and expansion. Fully 80% plan to boost capital spending next year. “Overall, chemical executives are telling us that they intend to put their money to work and boost investment in key areas, and almost two-thirds of executives say they’ll invest the capital before year-end,” says Michael J. Shannon, leader of KPMG’s chemicals practice. The bullishness comes despite uncertainty about the economy. Swiss chemi-
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cal maker Clariant lowered its 2011 profit prediction last week, citing the strong Swiss franc and “increasingly difficult economic conditions.” And stock analysts at Buckingham Research lowered earnings expectations by 10% or more for several U.S. chemical firms. The struggling economy will make growth difficult for chemical makers, Shannon explains, and set the stage “for increased expansion in emerging markets, M&A, and innovative product strategies as companies look to gain an edge.”—MICHAEL MCCOY
