Synthesis of bioactive fluoropyrrolidinesviacopper(i)-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides

Abstract

Chiral pyrrolidinyl units are important building blocks in biologically active natural products and drugs, and the develpment of efficient methods for the synthesis of diverse structured pyrrolidine derivatives is of...

Catalytic Enantioselective [3+2] Cycloaddition of N‐Metalated Azomethine Ylides

“…The highly enantioselective synthesis of fluoropyrrolidines 17 by Cu/L1 a-catalyzed asymmetric [3 + 2] cycloaddition of 1,1difluorostyrenes 16 with imino ester 1 was developed by Wang and Deng and co-workers. [26] The (S)-DTBM-Segphos L1 a was the best ligand, and the Cu source also played a crucial role in this process. The reaction of heterocycle-substituted imino esters gave products 17 g-h in diminished yield and enantioselectivity, but a number of chiral fluoropyrrolidines were obtained in yields of 54-96 % with high levels of diastereoselectivity and between 71-97 % enantioselectivities (Scheme 10).…”

“…The highly enantioselective synthesis of fluoropyrrolidines 17 by Cu/ L1 a ‐catalyzed asymmetric [3+2] cycloaddition of 1,1‐difluorostyrenes 16 with imino ester 1 was developed by Wang and Deng and co‐workers [26] . The ( S )‐DTBM‐Segphos L1 a was the best ligand, and the Cu source also played a crucial role in this process.…”

Electron-rich benzofulvenes as effective dipolarophiles in copper(i)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides

“…12 a , b With the aid of electron-withdrawing groups, a series of spiroindenes bearing an all-carbon quaternary stereocenter were smoothly formed in excellent yield and diastereoselectivity (Scheme 1c). In continuation of our research interest in azomethine ylide-involved catalytic asymmetric 1,3-dipolar cycloaddition reactions, 2 i , j ,13 we envisioned that benzofulvenes without any electron-withdrawing substituents may serve as 2π type dipolarophiles to participate in azomethine ylide-involved catalytic asymmetric 1,3-dipolar cycloadditions to enable the modular assembly of enantioenriched spiro-pyrrolidine derivatives. Nevertheless, several challenges may exist in the design: (1) whether reactivity driven by the intrinsic nonbenzenoid aromatic characteristic is enough for the novel dipolarophiles (benzofulvenes) because electron-withdrawing groups were inevitable in the previous [2 + 1] and [4 + 2] cycloadditions promoted by organocatalysts; (2) the control of chemo- and regioselectivity due to the existence of diverse electronic resonance structures in benzofulvene; (3) the construction of two contiguous all carbon quaternary centers including a challenging spiro chirality in a catalytic asymmetric manner.…”

11H-Benzo[4,5]imidazo[1,2-a]indol-11-one as a New Precursor of Azomethine Ylides: 1,3-Dipolar Cycloaddition Reactions with Cyclopropenes and Maleimides

“…Among the 1,3-dipoles, azomethine ylides (belonging to allyl-type N -centered dipoles) are among the most popular and frequently used in 1,3-dipolar cycloaddition reactions [ 3 , 4 ]. One of the most well-known methods for the preparation of azomethine ylides is the reaction of amines with aldehydes, followed by deprotonation of the iminium cation or a prototropic shift of the imine [ 5 , 6 ]. Amino acids are capable of reacting with aldehydes or ketones to generate intermediate oxazolidinones, which undergo decarboxylation, resulting in the formation of azomethine ylides [ 7 , 8 ].…”