Absolute Asymmetric Synthesis of “Chiral‐at‐Metal” Grignard Reagents and Transfer of the Chirality to Carbon

Abstract

Two new six-coordinate Grignard reagents, cis-[(p-CH(3)C(6)H(4))MgBr(dme)(2)] (1) and cis-[MgCH(3)(thf)(dme)(2)]I (2), have been synthesized and their crystal structures have been determined. Both reagents are cis-octahedral and therefore chiral. They crystallize as conglomerates and racemize rapidly in solution. By utilizing these properties, the absolute asymmetric synthesis of specifically the Delta or the Lambda enantiomer was achieved for both Grignard reagents. Enantiopure 1 and 2 were then reacted with butyraldehyde or benzaldehyde to give the corresponding alcohol in up to 22 % enantiomeric excess. At -60 degrees C, the Grignard reagents crystallize as racemic phases instead of conglomerates. Consequently, the crystal structures of rac-cis-[(p-CH(3)C(6)H(4))MgBr(dme)(2)].DME (3) and rac-cis-[MgCH(3)(thf)(dme)(2)]I (4) could be determined.

Absolute Asymmetric Synthesis of Stereochemically Labile Aldehyde Helicates and Subsequent Chirality Transfer Reactions

“…Crystallographic data for complexes 2-6. 153 (2) 193 (2) 143 (2) 123 (2) 123 (2) [8,9,[26][27][28] that yield enantiopure crystal batches without stirring. In these cases preferential crystallization is achieved by single-colony growth, a mechanism that also depends on secondary nucleation.…”

“…[7] Although these reactions frequently give products with high ee, they are limited to special (but very interesting) cases. We recently reported on a different approach; [8][9][10] chiral-at-metal Grignard reagents (of the [RMgX(LL) 2 ] type, see Scheme 1) can be subjected to total spontaneous resolution since they are stereochemically labile in solution. The resulting reagents were obtained in high yield and ee, and although they racemize quickly in solution, the chirality can be transferred (and thus trapped) to carbon (with an ee Abstract: Helical complexes formed between aluminum tris(2,6-diphenylphenoxide) (ATPH) and five different aldehydes have been prepared and structurally characterized by X-ray diffraction.…”

Spontaneous Resolution and Carbonation of Chiral Benzyllithium Complexes

“…In the case of the chiral reagents cis-[(p-CH 3 C 6 H 4 )MgBr(dme) 2 ] and cis-[Mg(CH 3 )(thf)(dme) 2 ]I, we found that conglomerates crystallise at ambient temperature, while racemic phases were obtained at -60°C. [6] In the case of 10-nitro-phenantren-9-yl sulfide,…”

“…In order to investigate this, similar complexes displaying Si or S atoms in the α-position were prepared and structurally characterized: [Li(tmsb)- secondary alcohols with up to 22 % ee on reaction with prochiral aldehydes. [6] The need to generate a new chirogenic centre in the product by asymmetric induction from the reagent probably explains the low enantiomeric excesses. Nevertheless, this was the first report of absolute asymmetric synthesis of an organometallic reagent; previous work on absolute asymmetric synthesis through total spontaneous resolution generally relies on photochemical rearrangement in chiral crystals or total spontaneous resolution of prochiral substrates, such as keto-compounds or alkenes.…”

Organic Solid-State Reactions

“…Chiral six-coordinated crystalline Grignard reagents (which were obtained by enantiomeric crystallization) were used for asymmetric solid-solid Grignard syntheses. For example, the (S)-alcohol was obtained with 10% ee when the Δ-crystal was comilled with butyric aldehyde (mp −96 ∘ C) at about liquid nitrogen temperature and after slow warming to room temperature and workup [128].…”