Catalytic Asymmetric Michael Additions of α-Cyanoacetates

Abstract

Enantiopure Michael addition products of a-cyanoacetates constitute attractive precursors for functionalised quaternary amino acids and other biologically interesting compounds. Since the pioneering work by Ito et al. in 1992 using rhodium(I) in combination with a trans-chelating planar chiral diphosphine, various complementary approaches have been reported; these are critically discussed and compared in this review. The most efficient recent methodologies utilise a bifunctional activation mode; for example, by dinuclear Lewis acid catalysis or by a well-defined hydrogenbonding network. This strategy can overcome the difficulty that acyanoacetates are incapable of two-point binding to a Lewis acid thus hampering the differentiation of prochiral enol(ate) faces.

Direct Catalytic Asymmetric Addition of Alkylnitriles to Aldehydes with Designed Nickel–Carbene Complexes

“…Nitriles, direct precursors of α‐cyanocarbanions, are generally stable and regarded as solvents for chromatography and various reactions owing to their inert nature toward a wide range of chemical transformations [1] . Acetonitrile is the most widely used nitrile‐based common solvent, but has little utility as a carbon pronucleophile in catalytic asymmetric reactions because 1) its high p K a (31.3 in DMSO) significantly interferes with catalytic generation of the corresponding α‐cyanocarbanion, [2–7] and 2) the minimal steric bias of the α‐cyanocarbanion significantly raises the hurdle for decent stereocontrol at the stage of carbon‐carbon bond formation with certain electrophiles (Scheme 1). Although recent advances in catalysis with well‐designed metal complexes allow for catalytic promotion of direct addition of acetonitrile to various electrophiles, [8] the issue of stereocontrol is more serious and has only been partly addressed [9, 10] .…”

Imbuing an Old Heterocycle with the Power of Modern Catalysis: An Isoxazolidin-5-one Story

“…25) Among them, β 2,2amino acids bearing two geminal substituents at the α-carbon are the most difficult to attain, and the available catalytic asymmetric synthesis route remains limited in terms of structural diversity. 26) In addition, most existing reports do not directly pertain to peptide synthesis, [27][28][29] which is unfortunate because peptides are the most sought-after products of β-amino acids. 30) At the outset of the author's research program, the α-quaternization of racemic isoxazolidin-5-ones was envisioned as a viable approach to tackle these existing problems (Chart 1).…”

Lewis Base Assisted Lithium Brønsted Base Catalysis: A New Entry for Catalytic Asymmetric Synthesis of β^2,2-Amino Acids

“…Hence, the development of a new method for synthesizing allcarbon quaternary analogs are highly sought after. 4,5) α-Functionalization of amino acid derived enolates is one of the most straightforward approaches to β 2,2 -amino acids. 6) Isoxazolidin-5-ones have been used as precursors for β-amino acids through the reductive cleavage of the N-O bond.…”