A chiral aldehyde-induced tandem conjugated addition–lactamization reaction for constructing fully substituted pyroglutamic acids

Abstract

A catalytic asymmetric tandem reaction including a chiral aldehyde catalyzed conjugated addition and an intramolecular lactamization is reported in this work. Under the optimal reaction conditions, various full-substituted pyroglutamic acids...

The Development of Aldehyde Catalytic System

“…This reaction was facilitated by the use of a chiral aldehyde C-19, enabling the efficient and highly stereoselective synthesis of pyroglutamic acids 61 with three vicinal chiral centers (Scheme 19). [52] A broad range of α,β-unsaturated diesters 60 substrates were compatible with this protocol, yielding the corresponding pyroglutamic acids 61 in good to excellent yields and diastereoselectivity, as well as good to high enantioselectivity under the optimized reaction conditions. Notably, α,β-unsatu- In the synthesis of unnatural amino acids, glycine plays a significant role as a key building block.…”

“…This reaction was facilitated by the use of a chiral aldehyde C‐19 , enabling the efficient and highly stereoselective synthesis of pyroglutamic acids 61 with three vicinal chiral centers (Scheme 19). [52] …”

Recent Advances in Chiral Aldehyde Catalysis for Asymmetric Functionalization of Amines

“…In 2022, Guo and co-workers 24 described a similar chiral-aldehyde-induced asymmetric tandem conjugate addition-lactamization process (Scheme 9). A variety of fully substituted pyroglutamic acids 21 with three vicinal chiral centers were constructed in good to excellent yields and stereoselectivities under the catalysis of the chiral aldehyde C2b.…”

Stereoselective synthesis of Δ(1)-pyrroline sulfonamides via a chiral aldehyde mediated cascade reaction

“…Chiral aldehyde catalysis has been proven to be a brilliant approach for the asymmetric α-functionalization of NH 2 -unprotected amino acid esters. 3–5 It is vital that the α-functionalized products have free amino groups that can participate as nucleophilic sites in subsequent cascade reactions to construct optically active nitrogen heterocyclic molecules (Scheme 1). In 2018, we disclosed the first chiral aldehyde catalyzed cascade reaction of glycinate, in which the conjugate addition and condensation occurred successively, resulting in optically active Δ(1)-pyrrolines (Scheme 1, eqn (1)).…”