Noncovalent Organocatalysis: A Powerful Tool for the Nucleophilic Epoxidation of α-Ylideneoxindoles

Abstract

A novel asymmetric nucleophilic epoxidation for α-ylideneoxindole esters has been successfully devised, resulting in enantioenriched spiro compounds with two new contiguous stereocenters. The employed (S)-α,α-diphenylprolinol functions as a bifunctional catalyst, creating a complex H-bond network in conjunction with a substrate and an oxidant.

Enantioselective Cascade Michael Addition/Cyclization Reactions of 3‐Nitro‐2H‐Chromenes with 3‐Isothiocyanato Oxindoles: Efficient Synthesis of Functionalized Polycyclic Spirooxindoles

“…Note that in these cases there was almost no hydrogen‐bonding interaction between ligands and substrate 2 a . These experimental observations substantially confirmed the postulated model of the transition state and explained the stereochemistry of the products 18d…”

Asymmetric Organocatalyzed Epoxidation of 2‐Oxoindoline‐3‐ylidene Acetaldehydes

“…The relative and absolute configuration of 12 and 13 were determined by comparison of the NMR spectra and optical rotation to reported data. [23] A postulated reaction mechanism is shown in Scheme 4. Both E/Z iminium ions would be formed from by combination of the amino-catalyst with the E/Z-mixture of 2-oxoindoline-3-ylidene acetaldehydes.…”

“…[22] Gasperi's group reported the asymmetric epoxidation of oxindole derivatives possessing b,b-disubstituted-a,b-unsaturated esters when catalyzed by diarylprolinol. [23] In 2010, we reported the asymmetric epoxidation of a-substituted-a,b-unsaturated aldehydes by using diphenylprolinol silyl ether as the chiral catalyst. [24] This organocatalyst was developed independently by our group [25] and Jørgensen's group [26] [Scheme 1a].…”

Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

“…Remarkably, diarylprolinols have shown promising performances in noncovalently activated reactions as well, and recent advances have been recently reviewed [59]. For instance, diphenylprolinol 33 and diarylprolinols 55 and 56 have been employed the enantioselective conjugate addition of N-heterocycles to α,β-enones (Figure 14a), and in the epoxidation of electron deficient olefins, such as enones acrylonitriles (Figure 14b), and useful building blocks such as α-ylidenoxindoles ( Figure 14c) [60][61][62][63][64]. For the first organocatalytic addition of benzotriazole (58) to the enone 57, the authors hypothesise an H-bond network acting in the transition state towards the induction of a moderate enantioselectivity in the subsequent formation of the product 59.…”

“…64 The substrate activation by BA is related to, though different from, H-bonding catalysis, since normally the formation of a H-bond precedes the transfer (partial or complete) of a proton. Moreover, some recent studies about BA catalysed imine activation suggest that besides ion pairing, due to the protonation of the substrate, H-bonding exists.…”