Department of Chemistry, University of Basel , BPR 1096, Postfach 3350, Mattenstrasse 24a, CH-4002 Basel, Switzerland.
Department of Biosystems Science and Engineering, ETH Zürich , Mattenstrasse 26, CH-4058 Basel, Switzerland.
J Am Chem Soc. 2017 Dec 6;139(48):17500-17507. doi: 10.1021/jacs.7b08976. Epub 2017 Nov 17.
Although iminium catalysis has become an important tool in organic chemistry, its combination with supramolecular host systems has remained largely unexplored. We report the detailed investigations into the first example of iminium catalysis inside a supramolecular host. In the case of 1,4-reductions of α,β-unsaturated aldehydes, catalytic amounts of host are able to increase the enantiomeric excess of the products formed. Several control experiments were performed and provided strong evidence that the modulation of enantiomeric excess of the reaction product indeed stems from a reaction on the inside of the capsule. The origin of the increased enantioselectivity in the capsule was investigated. Furthermore, the substrate and nucleophile scope were studied. Kinetic investigations as well as the kinetic isotope effect measured confirmed that the hydride delivery to the substrate is the rate-determining step inside the capsule. The exploration of benzothiazolidines as alternative hydride sources revealed an unexpected substitution effect of the hydride source itself. The results presented confirm that the noncovalent combination of supramolecular hosts with iminium catalysis is opening up new exciting possibilities to increase enantioselectivity in challenging reactions.
尽管亚胺催化已成为有机化学中的重要工具，但它与超分子主体系统的结合在很大程度上仍未得到探索。我们报告了首例超分子主体内亚胺催化的详细研究。在α,β-不饱和醛的 1,4-还原反应中，主体的催化量能够提高产物的对映过量。进行了几项对照实验，为反应产物对映过量的确实来自胶囊内部的反应提供了有力证据。研究了增加反应产物对映选择性的起源。此外，还研究了底物和亲核试剂的范围。动力学研究以及测量的动力学同位素效应证实，氢化物向底物的传递是胶囊内的速率决定步骤。对苯并噻唑烷作为替代氢源的探索揭示了氢源本身的意外取代效应。所呈现的结果证实，超分子主体与亚胺催化的非共价结合为在具有挑战性的反应中提高对映选择性开辟了新的令人兴奋的可能性。
