Asymmetric organocatalytic 1,4-additions provide access to a large number of biologically relevant compounds. Chiral squaramides efficiently catalyse enantioselective Michael addition of 1,3-dicarbonyl compounds to aliphatic nitroalkenes. The resulting γ-nitro carboxylic derivatives were obtained in high yields and in high enantiomeric purities. Quantum chemical calculations helped us to devise a transition state model, which explains the observed stereochemical course of the addition. The best results were obtained with Meldrum's acid as a donor, with which enantiomeric purity of the Michael adduct was 97 : 3 e.r. Using this methodology pregabalin was synthesized in three steps in overall 52% yield.
Diastereoselective ortho‐lithiation of ferrocenes is a principal strategy for the synthesis of chiral ferrocene ligands. Dilithiation of (R)‐1‐(2‐bromophenyl)‐1‐ferrocenyl‐N,N‐dimethylmethanamine leads to a dilithium intermediate, which can be transformed to a Taniaphos ligand with (R,Rp)‐configuration. On the other hand, lithiation of (R)‐1‐phenyl‐1‐ferrocenyl‐N,N‐dimethylmethanamine affords a lithiated product with opposite configuration of the stereogenic plane. Presumably, the second lithium atom attached at the ortho‐position of the phenyl ring is responsible for this difference through the intramolecular multicenter arrangement involving both lithium atoms and their adjacent carbon atoms, the iron atom of the ferrocenyl moiety, and the nitrogen atom of the amino group. This hypothesis has been supported also by quantum chemical calculations.
Diastereoselective ortho-lithiations serve for the preparation of many important chiral ferrocenes, however diastereoselections of these lithiations are explained only by simple steric models. We elucidated ortho-lithiations of three important ferrocenes based on DFT calculations. The calculations showed that simple models of transition states involving ferrocenyl substrates and lithium bases can only in some cases account for the experimental results. Transition state models, which include solvent or coordinating additives as distinct entities bound to lithium, can satisfactorily explain diastereoselection of the ortho-lithiations of chiral ferrocenes.
Copper(I) complexes of TADDOL‐based phosphane–phosphite ligands catalyze enantioselective conjugate additions of various Grignard reagents to cyclic enones. Through trapping of the resulting chiral magnesium enolates with N‐benzylidene‐4‐methylbenzenesulfonamide (as an imine) in one‐pot procedures, the corresponding Mannich products (i.e., β‐aminocarbonyl compounds) were obtained in good yields and high enantiomeric purities, although with only low diastereoselectivities.
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