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Science & Technology

May 17, 2010
Volume 88, Number 20
pp. 31 - 33

In Names, History And Legacy

Chemistry and culture collide in the coining of namesake reactions

Carmen Drahl

HANDY NAMES An iPhone app puts named reactions just a touch away. Synthetiq Solutions
HANDY NAMES An iPhone app puts named reactions just a touch away.
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RIVETING REACTIONS Named reactions are the topic of many books, a smattering of which are pictured here. Carmen Drahl/C&EN
RIVETING REACTIONS Named reactions are the topic of many books, a smattering of which are pictured here.

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To the casual observer, the periodic table is the only place to see chemists’ names in lights; organic chemists know better.

Just like atomic elements, organic chemistry reactions get names, too. It’s a fancified form of name dropping, usually to honor someone who had a hand in developing the reactions. Organic aficionados call them named reactions, and they are immensely popular—the topic of books, websites, even iPhone apps. And there’s nothing quite like a named reaction to put the human side of the science front and center.

That cultural crossroads comes to life in the story of the Heck reaction, also called the Mizoroki-Heck reaction. A chemist today would be hard-pressed to find an area that this reaction hasn’t touched, from pharmaceuticals to materials and beyond.

Mizoroki Tokyo Institute of Technology

Heck Pavel Kocovsky

In the late 1960s and early 1970s, Richard F. Heck and Tsutomu Mizoroki, the reaction’s namesakes, were in uncharted territory. Heck, working at the Delaware chemical firm Hercules, had a long-standing interest in transition-metal chemistry, something that wasn’t very common at the time. In 1968, he published a paper on a new carbon-carbon bond-forming reaction mediated by palladium, which coupled aromatic rings and alkenes (J. Am. Chem. Soc. 1968, 90, 5518). It was an exciting advance for palladium chemistry, which was just hitting its stride. But the reaction had a few drawbacks. For one thing, it required a full equivalent of a palladium salt, which was costly. And it worked best with aromatic rings substituted with toxic mercury or tin.

Half a world away at Tokyo Institute of Technology, Mizoroki, a young associate professor, was also exploring transition-metal chemistry. In 1971, he followed up on Heck’s work, reporting a reaction that coupled alkenes with iodine-substituted aromatic rings via a recyclable palladium catalyst, with no tin or mercury required (Bull. Chem. Soc. Jpn. 1971, 44, 581). This was the first example of the process that most chemists call the Heck reaction.

Heck, by then on the chemistry faculty at the University of Delaware, improved Mizoroki’s reaction conditions to make the process more practical (J. Org. Chem. 1972, 37, 2320). Mizoroki published one more report on the topic (Bull. Chem. Soc. Jpn. 1973, 46, 1505) before succumbing to pancreatic cancer at the age of 47, in 1980. By then, chemists were already starting to give the reaction a name.

It’s not entirely clear when organic chemists started naming reactions. The custom probably arose out of necessity, says László Kürti, a Damon Runyan Cancer Fellow at Harvard University and coauthor of a book on named reactions. “It makes communication so much easier,” he says. “If I had to explain an entire reaction every time, it would be very cumbersome.” Names are a form of shorthand, something for organic chemists to quickly recall and understand, he says.

Every organic chemist needs to understand the shorthand, so named-reaction references are a staple during graduate school and remain essential afterward. The Merck Index began including a section on named reactions in 1952, one of the first publications to do so. Since then, dozens more named-reaction books and websites have sprung up. There’s even a trio of named-reaction apps for the iPhone and iPod Touch. By making it easy to navigate between related content, apps help people make new connections between named reactions, says Stanford University graduate student Conrad Shultz, who codeveloped Named Reactions Pro and Lite apps with fellow graduate student David Thaisrivongs.

Of course, not every reaction gets a name. The vast majority of reactions never see use outside the discoverer’s lab. To deserve a name, a reaction has to be useful to a decent proportion of the chemistry community.

Realizing a reaction is useful can take time, says University of California, Berkeley, chemist Robert G. Bergman. In the 1970s, his team worked on an aromatic-ring-forming reaction. But it was more than a decade before the name “Bergman reaction” showed up. “It was only when people realized the reaction played a role in the way certain antitumor compounds work that it started getting attention,” Bergman explains.

The wait wasn’t long in Heck’s case. In 1971, three years after Heck’s first paper on his reaction, William P. Weber of the University of Southern California referred to “vinyl Heck reactions” in a publication (Tetrahedron Lett. 1971, 12, 4701). Weber was familiar with Heck’s work. He’d almost accepted a postdoc offer at Hercules with Heck, but ended up making other plans, Weber says. Weber’s team was trying to replace the mercury compounds Heck had used with silicon compounds. It seemed logical to use the phrase vinyl Heck reaction, he says. “My work was an extension. The original thought was his.”

Heck had cited Mizoroki in his seminal papers, but it was Heck’s name that was catching on.

Reactions get named for different reasons. Sometimes, names reflect the person who first discovered a reaction, and at other times someone they refer to who made the reaction practical enough to be used widely. In still other cases, a junior contributor gets credit. Not every named reaction is named for a person. Names such as the “aldol reaction” simply combine the words aldehyde and alcohol, sidestepping the identities of the reaction’s discoverers entirely. Abbreviations are also an option, as in the case of the ARO reaction, which means asymmetric ring-opening.

Naming can be a delicate proposition because attributing credit for a reaction isn’t always straightforward, explains organic chemist Eric N. Jacobsen of Harvard University. It’s easier when the same person who discovered a reaction is the one who makes it practical, but that isn’t always the case. “Sometimes, people will try to divide credit in order to take credit away from a key person,” he says. Other times, credit ends up shared by individuals who worked competitively, rather than cooperatively, he adds.

“There’s a fair amount of controversy in naming reactions—people get bent out of shape on occasion,” Bergman says.

It’s tough to pinpoint why some names stick and others don’t. “There are lots of people who try to have their methodology named,” says Jie Jack Li, a chemist at Bristol-Myers Squibb who has written several named-reaction books. But not everybody makes the cut. It’s only natural that the connections a chemist has amassed over time—classmate, mentor, student, department colleague, or friend—will play a role in whether names catch on, he explains. “It’s a combination of science and politics,” he says.

Names can spread by word of mouth and other social mechanisms, so “memory matters a lot,” says Jonah Berger, a social psychologist and professor of marketing at the University of Pennsylvania’s Wharton School who studies how ideas catch on. For example, scientific discoveries tend to be attributed to famous people. If several researchers author a key paper, most folks don’t remember all the names. “But you remember the famous person,” Berger says.

Considered one of the fathers of organometallic chemistry, Heck certainly fit the fame bill. “Heck was doing organometallic chemistry before most people knew it existed,” says Louis S. Hegedus of Colorado State University, who coauthored an early and influential textbook about the field.

Heck made far more contributions to chemistry than the reaction that bears his name, explains Douglass F. Taber, a former Heck colleague at the University of Delaware. Heck’s work, Taber says, laid the foundation for several reactions that are indispensable today, such as the Sonogashira reaction, another transition-metal-catalyzed coupling (J. Organomet. Chem. 1975, 93, 259).

“He was ahead of his time,” adds Victor A. Snieckus of Queen’s University, in Kingston, Ontario, in whose lab Heck carried out cobalt carbonyl chemistry, another original contribution, during a 2006 sabbatical. “He is long overdue for a Nobel Prize.”

By the 1990s, the Heck reaction was part of the chemistry vernacular. But the term “Mizoroki-Heck reaction” was also making appearances. In his 1995 book “Palladium Reagents and Catalysis,” pioneering organometallic chemist Jiro Tsuji, then at Okayama University of Science, in Japan, used the term. Tsuji knew Mizoroki in the 1960s and ’70s and has often referred to the Mizoroki-Heck reaction in lectures, reminding audiences of Mizoroki’s contributions, says organometallic chemist Tamejiro Hiyama of Kyoto University. Hiyama and others mentioned the Mizoroki-Heck reaction in publications in the late 1990s (such as Tetrahedron Lett. 1998, 39, 7893).

Having a namesake reaction “is an important way to keep from disappearing from the chemical scene.”

It’s important to recognize Mizoroki’s work, Tsuji says. “Neglect of previous work occurs in many cases, I know,” he writes in an e-mail. “Heck is a fair gentleman who cited the paper by Mizoroki correctly,” even though the Bulletin of the Chemical Society of Japan, where Mizoroki published his work, was “a rather minor journal at that time.”

The journal wasn’t on the radar of many American chemists back then, concurs John F. Hartwig, an organometallic chemist at the University of Illinois, Urbana-Champaign. “It wasn’t on my reading list as a grad student,” he says.

Reaction names almost never come to prominence after being introduced by a single individual or in a single journal or book, Berger notes. It’s really about a set of people, each making decisions that are interdependent. “What one person decides to call a reaction may affect what their student calls it,” he explains. Because networks of people are involved in naming, names aren’t set in stone. They can vary throughout the chemistry community, and they can change over time. These networks of decisions are playing out in books and journals every day.

A volume entitled “The Mizoroki-Heck Reaction” was published in 2009. But in a simple tally of journal articles to date, the number of appearances for “Heck reaction” still vastly outstrips occurrences of “Mizoroki-Heck reaction.”

“Heck deserves 95% of the credit” for the reaction, says UC Irvine chemist Larry E. Overman, whose own work has extended the reaction’s chemistry to making rings and new chiral centers. “I call it the Heck reaction, but I’ve published in books calling it the Mizoroki-Heck reaction,” he says.

“If some people think the reaction should be called ‘Mizoroki-Heck,’ that’s okay—it’s good to try to be inclusive,” Taber says.

Heck retired to Florida with his wife, Soccoro, in 1989 after having difficulty securing funding for his research. These days, he calls Soccoro’s native Philippines home. “I’m not doing any chemistry anymore, but I think I’ve done my share,” he says.

Asked what he thinks about the terms “Heck reaction” and “Mizoroki-Heck reaction,” he says he doesn’t have strong feelings either way. Mizoroki arrived at the reaction first, but “I wasn’t too far behind,” Heck says. Mizoroki didn’t follow up on the reaction or seem to recognize its value, he adds.

“Unfortunately, Mizoroki died quite young, before he could do much chemistry with palladium,” Heck says. “Maybe if he’d lived, it might’ve been called the Mizoroki reaction instead.”

Changes to reactions’ names matter because they mark a shift in the history of a reaction, and in a small way, the history of organic chemistry. Many prominent organic chemists don’t have a reaction named after them, but having a namesake reaction “is an important way to keep from disappearing from the chemical scene,” Bergman says. “In organic chemistry, it’s an important way to get famous.”

Named reactions captivate organic chemists because of their ties to people, to the field’s past and future, Li says. “We’re only human, after all.”

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2011 American Chemical Society
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