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Classic Addition Reaction Gets A Makeover

Chemical Synthesis: New catalyst expands stereochemical repertoire of alkene dichlorination

by Stu Borman
January 15, 2015 | A version of this story appeared in Volume 93, Issue 3

Structure of coventional approach and new syn reaction.
In conventional alkene anti-dichlorination (top), Cl+ and Cl attack opposite faces of the carbon-carbon double bond. In the new syn reaction (bottom), two Cl ions attack the same face, giving a stereoisomeric product.

In a development that could revise organic chemistry textbooks, a new catalytic version of alkene dichlorination makes the reaction more versatile.

Adding Cl2 to double-bonded carbons to give saturated dichlorinated products is a fundamental reaction taught early in the organic chemistry curriculum. It mostly proceeds in just one way: via an “anti” mechanism, in which Cl+ and Cl ions attack opposite faces of the double bond.

Now, researchers have devised the first catalytic alkene dichlorination that proceeds by the alternative “syn” route, in which two Cl ions attack the same face of the double bond. This approach provides a direct route to stereoisomers of anti-dichlorination products.

Chemists have reported alkene syn-dichlorinations before, using antimony and molybdenum chloride reagents, but these reactions were not catalytic and their applicability was severely restricted, primarily to nonsubstituted alkene substrates. The only other way to get alkene syn-dichlorination products has been to use multiple steps.

Alexander J. Cresswell, Stanley T.-C. Eey, and synthetic organic chemist Scott E. Denmark at the University of Illinois, Urbana-Champaign, have now designed a selenium(IV) reagent that catalyzes alkene syn-dichlorinations in one step (Nat. Chem. 2015, DOI: 10.1038/nchem.2141). They report 27 examples of cyclic and acyclic dichlorinated products synthesized using the strategy, including dichlorocyclohexane.

In the reaction, Se4+ gets reduced to Se2+. According to synthetic chemist Ross Denton of the University of Nottingham, in En­gland, the key to making the process catalytic was “identifying a suitable oxidant that would convert Se2+ back to Se4+ in the presence of the alkene and not interfere with the dichlorination process itself.” Denmark’s group did that, Denton says.

In a classic anti-dichlorination, Cl+ forms a cyclic intermediate on one side of the alkene. The ring is opened when Cl attacks the other side. In the syn-reaction, the Se4+ reagent forms a cyclic intermediate on one side of the alkene that is opened by Cl on the opposite side. The Se4+ reagent then gets displaced by a second Cl attacking on the same side as the first.

“The magic comes about from a deep-seated appreciation of reaction mechanism that follows from analytical thinking about the individual steps that constitute the process,” says synthetic organic chemist Erick M. Carreira of ETH Zurich. “The simplicity and availability of catalyst and reagents ensure that the method—and more generally, the concepts—will be widely adopted.”

Synthetic organic chemist Takehiko Yoshimitsu of Osaka University says the reaction “is a major breakthrough that could provide easier access to polychlorinated compounds, such as chlorosulfolipid natural products.”



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