Towards Substrate-Reagent Interaction of Lochmann-Schlosser Bases in THF: Bridging THF Hides Potential Reaction Site of a Chiral Superbase

Abstract

The metalation of N,N-dimethylaminomethylferrocene in THF by the superbasic mixture of ⁿ BuLi/KO^t Bu proceeds readily at low temperatures to afford a bimetallic Li₂ K₂ aggregate containing ferrocenyl anions and tert-butoxide. Starting from an enantiomerically enriched ortho-lithiated aminomethylferrocene, an enantiomerically pure superbase can be prepared. The molecular compound exhibits superbasic behavior deprotonating N,N-dimethylbenzylamine in the α-position and is also capable of deprotonating toluene. Quantum chemical calculations provide insight into the role of the bridging THF molecule to the possible substrate-reagent interaction. In addition, a benzylpotassium alkoxide adduct gives a closer look into the corresponding reaction site of the Lochmann-Schlosser base that is reported herein.

Keywords: X-ray diffraction; alkali metals; chirality; lithium; potassium.

Figure 1

Initial suggestion of the Lochmann–Schlosser base's key metalation agent and the different roles of its alkali metals; R=H, Alkyl.

Scheme 1

Deprotonation of DBA with organolithium compounds (left) and with a Lochmann–Schlosser base (right); R=Alkyl.

Scheme 2

Racemic approach for the synthesis of (rac)‐3.

Figure 2

Molecular structure of [(LiO ^t Bu)₂(FcKCH₂NMe₂)₂(THF)₃] (3; some hydrogen atoms and disorders are omitted for clarity). Symmetry‐equivalent positions are included to visualize the coordination environment of the metal centers (#1’: 1−x, y, 1−z). For further information see Supporting Information.

Figure 3

Possible pre‐coordination of toluene after a THF side‐detachment in compound 3.

Figure 4

Model of the different mechanisms how the THF molecules (simplified using DME instead of THF and DBA instead of FcCH₂NMe₂₎ in 3 could detach from the potassium centers and the corresponding calculated energy values. For more information see QM7–QM13 in the Supporting Information.

Figure 5

Possible pre‐coordination of toluene after a THF displacement in compound 3.

Scheme 3

Presentation of the energetically preferred THF displacement within 3.

Figure 6

Lewis formula of compound 4 representing the central structural motif within the crystal structure, which contains a benzyl anion that interacts with two potassium centers. The lines between the potassium cations are to clarify the structural motif.

Scheme 4

Stereoselective approach for the synthesis of (R _p)‐3.

Figure 7

Polymeric structure of [(PhCHKNMe₂)(THF)₂]_∞ (5; some hydrogen atoms and disorders are omitted for clarity). Symmetry‐equivalent positions are included to visualize the coordination environment of the potassium centers (#1’: +x, 3/2−y, 1/2+z). For further information see Supporting Information.

Scheme 5

Deprotonation of 1 with (R _p)‐3.