Unusual KIE and dynamics effects in the Fe-catalyzed hetero-Diels-Alder reaction of unactivated aldehydes and dienes
Open Access
- 15 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-10
- https://doi.org/10.1038/s41467-020-15599-w
Abstract
Hetero-Diels-Alder (HDA) reaction is an important synthetic method for many natural products. An iron(III) catalyst was developed to catalyze the challenging HDA reaction of unactivated aldehydes and dienes with high selectivity. Here we report extensive density-functional theory (DFT) calculations and molecular dynamics simulations that show effects of iron (including its coordinate mode and/or spin state) on the dynamics of this reaction: considerably enhancing dynamically stepwise process, broadening entrance channel and narrowing exit channel from concerted asynchronous transition states. Also, our combined computational and experimental secondary KIE studies reveal unexpectedly large KIE values for the five-coordinate pathway even with considerable C-C bond forming, due to equilibrium isotope effect from the change in the metal coordination. Moreover, steric and electronic effects are computationally shown to dictate the C=O chemoselectivity for an alpha,beta-unsaturated aldehyde, which is verified experimentally. Our mechanistic study may help design homogeneous, heterogeneous and biological catalysts for this challenging reaction.Funding Information
- National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (21672096, 21702095, and 21873043)
- SUSTech
This publication has 69 references indexed in Scilit:
- SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesisNature, 2017
- Electrostatic catalysis of a Diels–Alder reactionNature, 2016
- Industrial Applications of the Diels–Alder ReactionAngewandte Chemie, 2013
- Cationic Iron(III) Porphyrin-Catalyzed [4 + 2] Cycloaddition of Unactivated Aldehydes with Simple DienesJournal of the American Chemical Society, 2012
- Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn ANature, 2011
- Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder ReactionScience, 2010
- Single enantiomers from a chiral-alcohol catalystNature, 2003
- The Diels-Alder Reaction in Total SynthesisAngewandte Chemie, 2002
- Catalytic Asymmetric Hetero-Diels–Alder Reactions of Carbonyl Compounds and IminesAngewandte Chemie, 2000
- On the interactivity of chiral auxiliaries with chiral catalysts in the hetero Diels-Alder reaction: a new route to L-glycolipidsJournal of the American Chemical Society, 1983