NEWS OF TH E WEEK
C–C COUPLING REPERTOIRE GROWS REVIVAL This new reaction combines chiral secondary and tertiary boronic esters (left) with lithiated aryls to form intermediates that rearrange upon electrophile addition, yielding aryl-alkyl coupling products.
ORGANIC SYNTHESIS: Reaction eases addition of chiral carbon centers to aryl groups
T
HE REVIVAL of a nearly 50-year-old technique
for forming carbon-carbon bonds may help ease the synthesis of aryl derivatives, such as drug candidates. Varinder K. Aggarwal and coworkers at the University of Bristol, in England, have taken a venerable but neglected synthesis called Zweifel olefination and made it new again (Nat. Chem. 2014, DOI: 10.1038/nchem.1971). The team’s approach overcomes key limitations of Suzuki-Miyaura coupling, the reaction most often used in the pharmaceutical industry for creating C–C linkages. In Suzuki-Miyaura coupling, a O Ar transitionO R3 B R3 Ar Electrophile Ar–Li R3 B– metal catalyst O R1 R2 R1 R2 is used to join 1 2 R R sp2 carbon atoms (like those in aryl groups) to R1 to R3 = organic groups, Ar = aryl group one another. It cannot easily link sp2 to sp3 (single-bonded) carbon atoms, especially in a stereocontrolled manner. The new synthesis reported by Aggarwal and coworkers readily links sp2 carbon atoms to sp3 carbons with excellent stereocontrol and without use of transition metals. It reacts aryllithium reagents with chiral secondary or tertiary boronic esters to form aryl products with a chiral tertiary or quaternary carbon center (linked to three and four other carbons, respectively). “It is a special paper,” says organoboron chemist
Dennis G. Hall of the University of Alberta, Edmonton. “There is some precedent—there always is—but it achieves a feat that is virtually unachievable by regular Suzuki-Miyaura coupling.” “It obviates difficulties introduced by some of the side reactions often seen in transition-metal chemistry,” comments another organoboron chemist, Cathleen Crudden of Queen’s University, in Kingston, Ontario. “The fact that it can be employed for the generation of quaternary centers with high levels of enantiomeric purity is remarkable,” she says, noting that coupling reactions of that kind have generally not been available before. Earlier, Aggarwal’s group developed an enantioselective way to make secondary and tertiary boronic esters. “We were keen to find a way of coupling them to aromatics but recognized that this was a very difficult problem using classical Suzuki-Miyaura-based conditions,” he says. “We wondered whether we could take a leaf out of the Zweifel olefination reaction reported almost 50 years ago.” That reaction uses vinyllithium to make vinyl-alkyl products (J. Am. Chem. Soc. 1967, DOI: 10.1021/ ja00990a061 and 1968, DOI: 10.1021/ja01024a068). Aggarwal and coworkers substituted aryl for vinyl starting materials, optimized the process, and made it stereoselective. In the revived reaction, lithiated electron-rich aromatics and heteroaromatics are added to chiral secondary and tertiary boronic esters to form boronate intermediates. An electrophile such as N-bromosuccinimide is then added to induce a stereospecific rearrangement, eliminating the boronate and creating final products. The new reaction does have drawbacks. It tolerates only a limited range of functional groups on the starting materials and requires electron-rich aromatics. Aggarwal and coworkers are currently trying to expand the reaction’s scope to a broader range of functional groups and aromatics.—STU BORMAN
O
SUPPLY CHAIN BASF teams up with Chinese university to train its suppliers BASF and Shanghai’s East China University of Science & Technology have agreed to codevelop a training program for BASF’s 2,000 or so suppliers in China. The five-year program will cover topics including environmental protection, health and safety, and labor and human rights and strive to raise the sustainability standards of BASF’s Chinese suppliers. “China plays a vital role in BASF’s global supplier network,” says Fried Muenstermann, head of BASF’s procurement organization. In China, the firm buys basic chemicals, intermediates, functional raw materials, technical goods and services, and logistics services.
BASF says it chose East China University to work with its suppliers because the school is recognized for emphasizing business ethics and corporate social responsibility in educating Chinese managers and executives. BASF’s China training program falls under the umbrella of Together for Sustainability, an initiative started in 2011 by leading European chemical companies, including BASF, Bayer, and Evonik Industries, to promote sustainability across the chemical industry. Under the program, suppliers’ practices are audited by EcoVadis, a French organization that developed a method for measur-
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JUNE 16, 2014
ing corporate sustainability practices. Bringing Chinese suppliers up to global sustainability standards is a major undertaking for international chemical companies. The same week that BASF announced its cooperation with East China University, Lanxess, also a member of Together for Sustainability, organized a workshop on sustainability, health, safety, and environmental protection in Ningbo together with the China Petroleum & Chemical Industry Federation. Ningbo government officials, managers of the Ningbo Chemical Park, and foundation representatives attended the event.—JEAN-FRANÇOIS TREMBLAY
