Reversal in stereoselectivity depending upon the age of a chiral lithium alkoxyaluminohydride reducing agent

Synthesis of optically active N‐protected α‐aminoketones and α‐amino alcohols

“…Moreover, 1,2-amino alcohols have been the important building blocks in the synthesis of various natural products [1] and bicyclic amidines and guanidines [2]. In addition, the enantiomers of chiral amino alcohols could be employed in the asymmetric synthesis of optically active compounds [3], mainly by the formation of complex hydrides [4][5][6], or in the presence of metal catalysts [7,8] in the asymmetric reaction of unsaturated molecules. Therefore, the synthesis of optically active 1,2-amino alcohols has attracted much attention of the organic chemists.…”

1994 Merck Frosst Award Lecture New strategies for the stereoselective synthesis of natural and unnatural products via organometallic reagents and catalysts

“…Concurrent with our studies using cuprates and organolithium reagents with oxabicyclo[3.2.1 j substrates was elegant work by Arjona, Femandez de la Pradilla, Plumet and co-workers on the [2.2.1] series, eqs. [ l l j , [12] (18). …”

Solvent‐Dependent Enantiodivergent Mannich‐Type Reaction: Utilizing a Conformationally Flexible Guanidine/Bisthiourea Organocatalyst

“…[2] In contrast, recent findings from our group have shown that conformationally flexible guanidine/bisthiourea organocatalysts 1 [3][4][5][6][7] display unique stereodiscrimination processes that are governed by differential activation entropy (DDS°= 25.4 J mol À1 K À1 ) rather than differential activation enthalpy (DDH°=~0 kJ mol À1 ) in ortho-and enantioselective 1,4-type Friedel-Crafts alkylations of sesamol. [10] From the time of the disclosure by Mosher and co-workers in 1972 [11] on the asymmetric reduction of unsymmetric ketones with stoichiometric chiral alkoxyalminiumhydrides, several metal-based methodologies for enantiodivergent catalysis, in which the central metal and reaction conditions were tuned, have been studied. [9] The development of the solvent-dependent enantiodivergent Mannich-type reaction of N-aldimines with malonates that enable selective synthesis of either enantiomer by employing a single enantiomer of a chiral catalyst is presented (Scheme 1).…”

“…[8] A new perspective described herein concerns the possibility of bringing about dynamic control of the stereochemical outcomes in the organocatalytic system by tuning the enthalpy and entropy related external factors (e.g., reaction solvents, the substrate concentration, and pressure). [10][11][12] In these systems, individual metal properties, such as Lewis acidity, oxophilicity, azophilicity, and atomic radius, have been exploited for the formation of a variety monomeric and oligomeric catalytic active species. The S adducts are selectively formed with 87-94 % ee in reactions run in m-xylene, whereas R adducts predominate (80-89 % ee) in reactions carried out in acetonitrile.…”

“…[10] From the time of the disclosure by Mosher and co-workers in 1972 [11] on the asymmetric reduction of unsymmetric ketones with stoichiometric chiral alkoxyalminiumhydrides, several metal-based methodologies for enantiodivergent catalysis, in which the central metal and reaction conditions were tuned, have been studied. [10] From the time of the disclosure by Mosher and co-workers in 1972 [11] on the asymmetric reduction of unsymmetric ketones with stoichiometric chiral alkoxyalminiumhydrides, several metal-based methodologies for enantiodivergent catalysis, in which the central metal and reaction conditions were tuned, have been studied.…”