952661-06-2Relevant academic research and scientific papers
The asymmetric synthesis of amines via nickel-catalyzed enantioconvergent substitution reactions
Yang, Ze-Peng,Freas, Dylan J.,Fu, Gregory C.
, p. 2930 - 2937 (2021)
Chiral dialkyl carbinamines are important in fields such as organic chemistry, pharmaceutical chemistry, and biochemistry, serving for example as bioactive molecules, chiral ligands, and chiral catalysts. Unfortunately, most catalytic asymmetric methods for synthesizing dialkyl carbinamines do not provide general access to amines wherein the two alkyl groups are of similar size (e.g., CH2R versus CH2R1). Herein, we report two mild methods for the catalytic enantioconvergent synthesis of protected dialkyl carbinamines, both of which use a chiral nickel catalyst to couple an alkylzinc reagent (1.1-1.2 equiv) with a racemic partner, specifically, an α-phthalimido alkyl chloride or an N-hydroxyphthalimide (NHP) ester of a protected α-amino acid. The methods are versatile, providing dialkyl carbinamine derivatives that bear an array of functional groups. For couplings of NHP esters, we further describe a one-pot variant wherein the NHP ester is generated in situ, allowing the generation of enantioenriched protected dialkyl carbinamines in one step from commercially available amino acid derivatives; we demonstrate the utility of this method by applying it to the efficient catalytic enantioselective synthesis of a range of interesting target molecules.
A versatile annulation protocol toward novel constrained phosphinic peptidomimetics
Nasopoulou, Magdalini,Georgiadis, Dimitris,Matziari, Magdalini,Dive, Vincent,Yiotakis, Athanasios
, p. 7222 - 7228 (2008/02/12)
(Chemical Equation Presented) The development of a novel 3-center 2-component annulation reaction between α,ω-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting α,ω-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochemistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.
