Understanding Selectivity of Lithiated Intermediates for Synthesis

• Applicant: Professor Dr. Carsten Strohmann
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2010 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 164195656

• Final Report Year: 2018

Final Report Abstract

Within the framework of this project, structure and reactivity patterns of organolithium compounds and Lochmann-Schlosser’s Base mixtures as well as novel superbasic mixtures become important in the carbometalation and deprotonation reaction. Allylamines could be selectively deprotonated. The use of further coordinating groups within the allylamine made it possible to suppress the carbolithiation reaction in the presence of organolithium compounds. Additionally, the treatment with mixed metal systems such as the Lochmann-Schlosser’s Base mixture or its sodium analogue lead to a selective deprotonation. In case of the piperidinoallylamine, the carbolithiation reaction could be carried out and electrophiles react selectively in benzylic or para-position. The use of sufficient solvents and their corresponding structures were the key factors for the control of the reaction’s regioselectivity. Studies were carried out to stabilize the phenethylamine anion. Quantum chemical calculations showed that the introduction of a further stabilizing phenyl group favored the metalated product over the elimination of the amine. Due to these results, the phenethylamine was not only synthesized through a deprotonation reaction but also through an aminometalation reaction of 4-methoyxstyrene, a potassium dimethylamine and a lithium alkoxide. A possible reactive species was isolated and characterized through x-ray crystalography. An extensive investigation to find novel superbasic mixtures derived from the Lochmann-Schlosser’s Base mixture has been carried out. If lithium and sodium aminoalkoxides or siloxides are used, the choice of organolithium compound becomes important. In case of the potassium analogues, the reactivity of the mixture is independent of the alkyllithium and the desired product formation is observed for all tested mixtures. Possible reactive species of mono and mixed metal systems were isolated and characterized through x-ray crystallography. One monometallic aggregate even included “monomeric” n-butyllithium which is the first of its kind. The mixed metal aggregate is only the third structure isolated containing all four components of a superbasic mixture.

Publications

• Mechanistic Insight into Stereoselective Carbolithiation: Chem. Eur. J. 2011, 17, 2996-3004
  Gessner, Viktoria H.; Koller, Stephan G.; Strohmann, Carsten; Hogan, Anne‐Marie & O'Shea, Donal F.
  
• Direct Benzylic Metalation of a Phenethylamine Derivative: Potassium as the Key to both Generation and Stabilization of a “Labile Anion”: Chem. Commun. 2012, 48, 10612-10614
  Unkelbach, Christian; Rosenbaum, Hannah S. & Strohmann, Carsten
  
• Isolation of reactive intermediates in deprotonation reactions with zinc alkyls: Chem. Commun. 2012, 48, 5034-5036
  Colquhoun, Victoria P.; Unkelbach, Christian & Strohmann, Carsten
  
• Insights into the Metalation of Benzene and Toluene by Schlosser's Base: A Bimetallic, Superbasic Cluster comprising PhK, PhLi and tBuOLi: Angew. Chem. Int. Ed. 2014, 53, 553-556
  Unkelbach, Christian; O'Shea, Donal F. & Strohmann, Carsten
  
• A Route to Stereochemically Pure Benzyllithium Reagents by Stereocontrolled Epimerisation: Chem. Eur. J. 2015, 21, 641-647
  Koller, Stephan G.; Kroesen, Ulrike & Strohmann, Carsten
  
• Unexpected Structural Motifs in Diamine Coordination Compounds with Allyllithium: Chem. Commun. 2014, 50, 2532-2534
  Eckert, Prisca K.; Schnura, Barbara & Strohmann, Carsten
  
• Controlling the coordination sphere of alkyllithiums results in selective reactions with allylic amines: Angew. Chem. Int. Ed. 2017, 56, 14164-14168
  Kroesen, Ulrike; Unkelbach, Christian; Schildbach, Daniel & Strohmann, Carsten
  
• Exploring Planar Chiral Amino Siloxides: Angew. Chem. Int. Ed. 2017, 56, 8295-8298
  Golz, Christopher; Steffen, Patricia & Strohmann, Carsten
  
• Selective Si-C(sp3) Bond Cleavage in (Aminomethyl)silanes by Carbanionic Nucleophiles and its Sterochemical Course: Angew. Chem. Int. Ed. 2017, 56, 7991-7994
  Koller, Stephan G.; Bauer, Jonathan O. & Strohmann, Carsten
  
• The Reactivity of Benzyl Lithium Species is Regulated by Intermediate Structures: Angew. Chem. Int. Ed. 2017, 56, 6232-6235
  Kroesen, Ulrike; Knauer, Lena & Strohmann, Carsten