Catalytic asymmetric Mannich-type reactions of fluorinated ketoesters with N-Boc aldimines in the presence of chiral palladium complexes

Recent progress in the asymmetric Mannich reaction

“…In 2011, Kang and Kim [13] developed the highly efficient catalytic enantioselective Mannich reaction of α-fluoro-βketoesters catalysed by chiral palladium complexes (2) which are air-and moisture-stable. The desired β-aminated products were obtained in good to high yields, and high enantioselectivities (up to 99% ee) were observed for all the substrates examined in this work.…”

“…The substrate scope and limitations of the first-generation system remained problematic. After mechanistic studies on the catalyst prepared from Sm(O-iPr)3, they reoptimized the catalyst preparation method, and a catalyst derived from Sm5O(O-iPr) 13 showed broader substrate generality as well as higher reactivity and stereoselectivity compared to Sm(O-iPr)3. The optimal system with Sm5O(O-iPr)13 was applicable to various aromatic, heteroaromatic, and isomerizable aliphatic N-Boc imines, giving products in 66-99% ee and syn/anti >20:1-13:1.…”

Stereoselective Organocatalyzed Synthesis of α‐Fluorinated β‐Amino Thioesters and Their Application in Peptide Synthesis

“…However, the stereoselective synthesis of even non-activated a-fluoro-b-amino acids is not straightforward. [3,[6][7][8][9] Enantioselective Mannich-type addition reactions of a-fluoroenolates are an attractive option for reaching this goal. [8,9] However, strategies reported so far provided addition products that cannot be readily incorporated into peptides and offer only limited possibilities for orthogonal derivatization.…”

“…[3,[6][7][8][9] Enantioselective Mannich-type addition reactions of a-fluoroenolates are an attractive option for reaching this goal. [8,9] However, strategies reported so far provided addition products that cannot be readily incorporated into peptides and offer only limited possibilities for orthogonal derivatization. [8,9] Moreover, their scope is typically limited to aromatic imine substrates, and comparatively high catalyst loadings are required.…”

“…[8,9] However, strategies reported so far provided addition products that cannot be readily incorporated into peptides and offer only limited possibilities for orthogonal derivatization. [8,9] Moreover, their scope is typically limited to aromatic imine substrates, and comparatively high catalyst loadings are required. [8,9] Herein we present highly stereoselective Mannich-type addition reactions of a-fluori-nated monothiomalonates (F-MTMs) with imines under mild organocatalytic conditions.…”