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New Spin On Stereocontrol

Catalysis: Molecular motor takes turns at making each enantiomer, racemate in addition reaction

by Bethany Halford
February 14, 2011 | A version of this story appeared in Volume 89, Issue 7

Credit: Science
In one position (left), the molecular motor catalyst guides reactants to a product with S stereochemistry. In another position (right), adducts with R stereochemistry form. (C = turquoise, N = blue, F = purple, O = red, S = gray, H = white)
Credit: Science
In one position (left), the molecular motor catalyst guides reactants to a product with S stereochemistry. In another position (right), adducts with R stereochemistry form. (C = turquoise, N = blue, F = purple, O = red, S = gray, H = white)

Challenging those who think molecular motor makers are just spinning their wheels, chemists in the Netherlands have created a rotary motor catalyst capable of dynamically controlling the chiral space in a catalytic asymmetric addition reaction (Science, DOI: 10.1126/science.1199844). The motor molecule can make a racemate, R enantiomer, or S enantiomer on demand, depending upon where it is in its rotary cycle.

“As far as we know the system is unique,” says Ben L. Feringa, the University of Groningen chemistry professor who created the motor with coworker Jiaobing Wang. Previous examples of chiral catalysts with this kind of switching ability rely on solvent changes, temperature variation, or addition of a Lewis acid, Feringa says, and their catalytic behavior is usually difficult to predict. This molecular motor catalyst, he continues, allows his team to control the stereoselectivity of the reaction through noninvasive external signals—light and heat.

“Molecular motors provide us with a great starting point for a multistage chiral catalyst design,” Feringa points out. “They have the intrinsic ability to change chirality in response to light.” As a result, he says, researchers can control how the motors turn in order to make products of different stereochemistries.

The molecular motor catalyst consists of two arms that turn past one another in a unidirectional manner in four discrete steps. One arm is equipped with a 4-dimethylaminopyridine (DMAP) moiety while the other features a thiourea group. When these two groups are pointed away from each other, the catalytic motor generates a racemic mixture of products in the conjugate addition of 2-methoxythiophenol to cyclohexenone.

Shine light on the catalyst and its double-bond axle isomerizes, bringing the arms and their cooperative catalytic groups into close proximity. Here the thiourea group holds the cyclohexenone in place while the DMAP unit guides the thiophenol to stereoselectively form the addition product with S stereochemistry in an S to R enantiomeric ratio of 75 to 25. Heating the system up to 70 °C forces the arms to pass one another, so that the DMAP now sends the thiophenol to the other side of the cyclohexenone, preferentially forming the product with R stereochemistry in an S to R enantiomeric ratio of 23 to 77. Light prompts the double bond to isomerize again and sends the arms back to their starting positions.

Feringa notes that other chiral catalysts give higher enantioselectivities for similar reactions, “but that is not the issue. Our goal was not to demonstrate yet another organocatalytic reaction but to test a concept and show that different rates and stereoselectivities can be reached as a catalyst adapts itself in response to an external signal,” he says. “The unidirectional light-driven motor gave us a nice opportunity to realize such adaptive functional behavior.”

“The fact that Wang and Feringa have designed an integrated supramolecular system that brings together molecular recognition, chirality transfer, catalysis, stereoelectronic control, and enantioselectivity is remarkable to say the least,” comments Northwestern University chemistry professor and molecular machine expert Sir J. Fraser Stoddart. “The realization, however, that all of these processes can be enabled or disabled by attenuating catalytic activity in one fell swoop in ways that are internally consistent in an absolute, as well as a relative, stereochemical sense raises the creativity bar in synthetic chemistry onto a whole new level of sophistication.”

“I found this combination of motor and catalytic function ingenious,” adds Boston College chemistry professor and molecular motor maker T. Ross Kelly. “It is especially gratifying when an idea this pretty actually works.”


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