If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.



Coaxing chiral products from an SN1 reaction

Quaternary stereocenters generated via combination of a chiral hydrogen-bond-donor catalyst and a Lewis acid

by Bethany Halford
April 30, 2018 | A version of this story appeared in Volume 96, Issue 18

A racemic tertiary propargyl acetate is transformed into a single enantiomer with a quaternary stereocenter.

One of the first reactions organic chemistry students learn is the unimolecular nucleophilic substitution, or SN1. Yet SN1 reactions are unpopular among chemists, largely because chiral molecules made in this manner wind up as a racemic mixture of both enantiomers. But now, Harvard University chemists Eric N. Jacobsen, Alison E. Wendlandt, and Prithvi Vangal report a method to produce quaternary stereocenters via the SN1 reaction (Nature 2018, DOI: 10.1038/s41586-018-0042-1). The chemists use a chiral squaramide catalyst, which acts as a dual hydrogen-bond donor, in combination with the strong Lewis acid trimethylsilyl trifluoromethanesulfonate. This catalyst system promotes formation of a planar carbocation, as happens normally in SN1 reactions. However, it sidesteps elimination reactions that plague typical SN1 chemistry, and guides the nucleophile’s approach to just one face of the carbocat­ion, so that the chemists could transform racemic tertiary propargyl acetates into compounds with quaternary stereocenters (example shown). Although similar strategies have been deployed to make chiral products from cationic intermediates, such examples have been limited to heteroatom-stabilized carbocations, which are less likely to rearrange or generate elimination products.


This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.