Ag(I)/CAAA-Amidphos Complex Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Acrylates for the Formal Synthesis of (+)-Ibophyllidine

In this work, we introduced a multifunctional Ag(I)/CAAA-amidphos complex catalyzed asymmetric 1,3-dipolar cycloaddition of acrylates with α-imino esters, affording a series of 2,4,5-trisubstituted endo-pyrrolidines in good yields (up to 97%) with high enantioselectivities (up to 98% ee). Meanwhile, the catalytic system was also applied in the three-component one-pot reaction of α-imino esters formed in situ under the action of N,N′-diisopropylcarbodiimide. In addition, the gram-scale reaction was realized for the formal synthesis of (+)-ibophyllidine in eight steps.

In the Pursuit of (Ald)Imine Surrogates for the Direct Asymmetric Synthesis of Non-Proteinogenic α-Amino Acids

Nature remarkably employs posttranslational modifications of the 20 canonical α-amino acids to devise a far larger structural, conformational, and functional diversity found in non-proteinogenic amino acids (NPAAs) which ultimately translates into a plethora of complex biological functions. Synthetic chemists are continuously trying to reproduce and even extrapolate the repertoire of NPAA building blocks to build structural diversity into bioactive molecules and materials. The direct asymmetric functionalization of α-imino esters represents one of the most robust and attractive routes to NPAAs. This review summarizes the most prominent examples of bench-stable (ald)imine surrogates exploited for the synthesis of NPAAs including our most recent results in the nucleophilic substitution of α-haloglycines and other α-haloaminals. A synopsis of kinetic studies, reaction optimizations, and enantioselective catalytic methods is also presented.

Zinc salt-catalyzed reduction of α-aryl imino esters, diketones and phenylacetylenes with water as hydrogen source

The zinc salt-catalyzed reduction of α-aryl imino esters, diketones and phenylacetylenes with water as hydrogen source and zinc as reductant was successfully conducted.

Organocatalytic regio-, diastereo- and enantioselective γ-additions of isoxazol-5(4H)-ones to β,γ-alkynyl-α-imino esters for the synthesis of axially chiral tetrasubstituted α-amino allenoates

The chiral phosphoric acid catalyzed regio-, diastereo- and enantioselective reaction of isoxazol-5(4H)-ones with β,γ-alkynyl-α-imino esters has been developed.

Stereodivergent Pd/Cu catalysis: asymmetric alkylation of racemic symmetrical 1,3-diphenyl allyl acetates

A stereodivergent Pd/Cu catalyst system was developed, which was successfully applied to the asymmetric allylic alkylation of symmetrical 1,3-disubstituted allyl acetates with prochiral imino esters in a fully stereodivergent manner.

Cu(I)-catalyzed asymmetric exo-selective synthesis of substituted pyrrolidines via 1,3-dipolar cycloaddition reaction

A (R)-DM-BINAP/Cu(CH3CN)4BF4 complex catalyzed exo-selective asymmetric 1,3-dipolar cycloaddition reaction (1,3-DCA) of imino esters with α,β-unsaturated pyrazoleamides has been developed. A series of highly functionalized pyrrolidines with multiple stereogenic centers was...

Ni-catalyzed asymmetric hydrogenation of N-aryl imino esters for the efficient synthesis of chiral α-aryl glycines

Chiral α-aryl glycines play a key role in the preparation of some bioactive products, however, their catalytic asymmetric synthesis is far from being satisfactory. Herein, we report an efficient nickel-catalyzed asymmetric hydrogenation of N-aryl imino esters, affording chiral α-aryl glycines in high yields and enantioselectivities (up to 98% ee). The hydrogenation can be conducted on a gram scale with a substrate/catalyst ratio of up to 2000. The obtained chiral N-p-methoxyphenyl α-aryl glycine derivatives are not only directly useful chiral secondary amino acid esters but can also be easily deprotected by treatment with cerium ammonium nitrate for further transformations to several widely used molecules including drug intermediates and chiral ligands. Formation of a chiral Ni-H species in hydrogenation is detected by 1H NMR. Computational results indicate that the stereo selection is determined during the approach of the substrate to the catalyst.