Details

Autor(en) / Beteiligte

• Wahlers, Jessica
• Margalef, Jèssica
• Hansen, Eric
• Bayesteh, Armita
• Helquist, Paul
• Diéguez, Montserrat
• Pàmies, Oscar
• Wiest, Olaf
• Norrby, Per-Ola

Titel

Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

Ist Teil von

• Nature communications, 2021-11, Vol.12 (1), p.6719-6719, Article 6719

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome. A predictive model has been created for a stereoselective palladium-catalysed allylic amination reaction. Derived only from quantum chemical data, the method is accurate enough to reveal multiple erroneous assignments in literature experiments.