A change to the canon of organic chemistry appears to be in order. Chemists at the University of California, Berkeley, report an SN2 reaction that proceeds with retention of stereochemical configuration (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja508799p). The reaction takes place within an organogallium host.
Students of organic chemistry learn early on that SN2 reactions are characterized by inversion of stereochemical configuration. The incoming nucleophile displaces the leaving group on a carbon atom through a so-called backside attack that flips the arrangement of the carbon’s three other substituents. It’s akin to an umbrella becoming inverted by a strong gust of wind.
Chen Zhao, F. Dean Toste, Kenneth N. Raymond, and Robert G. Bergman discovered they could make the reaction proceed with stereochemical retention quite by accident. They’d come across a clever way of making single diastereomers of so-called nanovessel hosts and hoped to use them in asymmetric reactions. But when they tried to use the nanovessel for a substitution reaction on a racemic mixture of a benzylic substrate with the hope of getting primarily one enantiomer of product, their results were disappointing.
So, they looked at what happened when they did the same reaction on a single enantiomer of the benzylic substrate. Much to their surprise, the reaction proceeded with up to 90% retention of stereochemical configuration.
“We think that what we’re seeing is a kind of double inversion,” Bergman explains. As the leaving group departs, the π-electrons from one of the naphthalene groups that make up the nanovessel’s walls interact with the backside of the developing carbocation in the benzylic substrate. This sort of interaction has been observed before with neighboring groups within a substrate molecule but never intermolecularly.
“This paper is a great combination of good, old-fashioned sleuthing applied to the frontiers area of supramolecular host-guest catalysis,” comments Ryan A. Shenvi, an organic chemist at Scripps Research Institute, in La Jolla, Calif., who has also tinkered with the canon of SN2 reactions. “It’s easy to imagine many more discoveries snowballing from this single observation,” he says.
INSIDE THE HOST
See what it's like to be the guest molecule inside the UC-Berkeley group's host complex.