Chiral Products from an SN 1 Reaction Coaxing-有机合成与工艺文献分享
Nature 2018, 556, 447. DOI: 10.1038/s41586-018-0042-1
◆One of the first reactions organic chemistry students learn is the unimolecular nucleophilic substitution, or SN1. Yet SN1 reactions are unpopular among chemists丑女也疯狂 ,房艺谈 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平嶋夏海 , Alison E.Wendlandt小唐璜情史 , and Prithvi Vangal report a method to produce quaternary stereocenters via the SN1 reaction.
◆The chemists use a chiral squaramide catalyst饕餮女 , which acts as a dualhydrogen-bond donor, in combination with the strong Lewis acid trimethylsilyl trifluoromethanesulfonate.
Powerful Pairing Spurs Lewis acids for Asymmetric Catalysis
◆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 carbocat-ion木乐吧 , so that the chemists could transform racemic tertiary propargyl acetates into compounds with quaternary stereocenters.
◆Although similar strategies have been deployed to make chiral products from cationic intermediates宠奴的逆袭 , such examples have been limited to heteroatom-stabilized carbocations, which are less likely to rearrange orgenerate elimination products.