Understanding Selectivity of Lithiated Intermediates for Synthesis
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
V.H. Gessner, S.G. Koller, C. Strohmann, A.- M.L. Hogan, D.F. O’Shea
(See online at https://dx.doi.org/10.1002/chem.201000814) - 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
C. Unkelbach, H.S. Rosenbaum, C. Strohmann
(See online at https://dx.doi.org/10.1039/c2cc35888c) - Isolation of reactive intermediates in deprotonation reactions with zinc alkyls: Chem. Commun. 2012, 48, 5034-5036
V.P. Colquhoun, C. Unkelbach, C. Strohmann
(See online at https://dx.doi.org/10.1039/c2cc32057f) - 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
C. Unkelbach, D.F. O'Shea, C. Strohmann
(See online at https://doi.org/10.1002/anie.201306884) - Unexpected Structural Motifs in Diamine Coordination Compounds with Allyllithium: Chem. Commun. 2014, 50, 2532-2534
P.K. Eckert, B. Schnura, C. Strohmann
(See online at https://doi.org/10.1039/c3cc48873j) - A Route to Stereochemically Pure Benzyllithium Reagents by Stereocontrolled Epimerisation: Chem. Eur. J. 2015, 21, 641-647
S.G. Koller, U. Kroesen, C. Strohmann
(See online at https://doi.org/10.1002/chem.201405152) - Controlling the coordination sphere of alkyllithiums results in selective reactions with allylic amines: Angew. Chem. Int. Ed. 2017, 56, 14164-14168
U. Kroesen, C. Unkelbach, D. Schildbach, C. Strohmann
(See online at https://doi.org/10.1002/anie.201708620) - Exploring Planar Chiral Amino Siloxides: Angew. Chem. Int. Ed. 2017, 56, 8295-8298
C. Golz, P. Steffen, C. Strohmann
(See online at https://doi.org/10.1002/anie.201703701) - Selective Si-C(sp3) Bond Cleavage in (Aminomethyl)silanes by Carbanionic Nucleophiles and its Sterochemical Course: Angew. Chem. Int. Ed. 2017, 56, 7991-7994
S.G. Koller, J.O. Bauer, C. Strohmann
(See online at https://doi.org/10.1002/anie.201702410) - The Reactivity of Benzyl Lithium Species is Regulated by Intermediate Structures: Angew. Chem. Int. Ed. 2017, 56, 6232-6235
U. Kroesen, L. Knauer, C. Strohmann
(See online at https://doi.org/10.1002/ange.201702377)
