Issue 5, 2017

Anion–π catalysis: bicyclic products with four contiguous stereogenic centers from otherwise elusive diastereospecific domino reactions on π-acidic surfaces

Abstract

Anion–π interactions have been introduced recently to catalysis. The idea of stabilizing anionic intermediates and transition states on π-acidic surfaces is a new fundamental concept. By now, examples exist for asymmetric enolate, enamine, iminium and transamination chemistry, and the first anion–π enzyme has been created. Delocalized over large aromatic planes, anion–π interactions appear particularly attractive to stabilize extensive long-distance charge displacements during domino processes. Moving on from the formation of cyclohexane rings with five stereogenic centers in one step on a π-acidic surface, we here focus on asymmetric anion–π catalysis of domino reactions that afford bicyclic products with quaternary stereogenic centers. Catalyst screening includes a newly synthesized, better performing anion–π version of classical organocatalysts from cinchona alkaloids, and anion–π enzymes. We find stereoselectivities that are clearly better than the best ones reported with conventional catalysts, culminating in unprecedented diastereospecificity. Moreover, we describe achiral salts as supramolecular chirality enhancers and report the first artificial enzyme that operates in neutral water with anion–π interactions, i.e., interactions that are essentially new to enzymes. Evidence in support of contributions of anion–π interactions to asymmetric catalysis include increasing diastereo- and enantioselectivity with increasing rates, i.e., asymmetric transition-state stabilization in the presence of π-acidic surfaces and inhibition with the anion selectivity sequence NO3 > Br > BF4 > PF6.

Graphical abstract: Anion–π catalysis: bicyclic products with four contiguous stereogenic centers from otherwise elusive diastereospecific domino reactions on π-acidic surfaces

Supplementary files

Article information

Article type
Edge Article
Submitted
03 Febr. 2017
Accepted
16 Febr. 2017
First published
17 Marts 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 3770-3774

Anion–π catalysis: bicyclic products with four contiguous stereogenic centers from otherwise elusive diastereospecific domino reactions on π-acidic surfaces

L. Liu, Y. Cotelle, J. Klehr, N. Sakai, T. R. Ward and S. Matile, Chem. Sci., 2017, 8, 3770 DOI: 10.1039/C7SC00525C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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