Enantioselective Michael Addition of 3-Aryl-Substituted Oxindoles to Methyl Vinyl Ketone Catalyzed by a Binaphthyl-Modified Bifunctional Organocatalyst

Lee, Hyun Joo; Woo, Saet Byeol; Kim, Dae Young

doi:10.3390/molecules17067523

Cited by 29 publications

(3 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our results and previously studies, plausible stereochemical model was proposed as shown in Figure . We proposed that o ‐QMs 1 was activated by hydrogen bonding with a squaramide moeity of chiral binaphthyl‐catalyst III and malonitrile ( 2a ) was deprotonated by the tertiary amine of catalyst, followed by subsequent enantioselective addition of malonitrile ( 2a ) to o ‐QMs 1 with the re ‐face.…”

Section: Optimization Of the Reaction Conditionsmentioning

confidence: 62%

Enantioselective Organocatalytic Michael Addition and Ring Closure Cascade Reaction of o‐Quinone Methides with Nitriles

Park

Jang

Choo

et al. 2020

Bulletin Korean Chem Soc

Self Cite

View full text Add to dashboard Cite

The 4H-chromene core exist in a number of natural products with various biological activities. 1 Among the 4Hchromene derivatives, the 2-amino-4H-chromenes have attracted substantial attention in medicinal chemistry due to their diverse range of pharmacological activities mediated via anti-inflammatory, antimicrobial, antiviral, and anticancer effects. 2 The ortho-quinone methides (o-QMs) are viable intermediates in synthetic organic chemistry, chemical biology, and material chemistry. 3 Substantial progress has been made in the conjugate addition to o-QMs with Michael donors in organocatalysis, 4 and transition-metal catalysis. 5 Further, o-QMs have emerged as formal 1,4-dipoles that react with various two-carbon reaction partners to afford six-membered oxacyclic compounds. Recently, the Han group reported organocatalytic asymmetric annulation of o-QMs with malonitrile to obtain 2-amino-4H-chromene derivatives with high enantioselectivity. 6 Nonetheless, a more efficient approach for the enantioselective synthesis of 2-amino-4H-chromenes is still highly desired.In connection with our research program investigating asymmetric catalysis, 7 we have reported the decarboxylative alkylation of β-keto acids to o-QMs derived from o-hydroxy benzylic alcohols. 8 Herein, we present the enantioselective organocatalytic conjugate addition and cyclization sequences of nitriles to o-QMs.To determine the optimized reaction conditions for the enantioselective organocatalytic conjugate addition and cyclization cascade of nitriles to o-QMs, we investigated a reaction system with o-QM 1a and malonitrile (2a) in the presence of 5 mol % of organocatalyst. We first surveyed the efficiency of binaphthyl-based bifunctional organocatalysts I-VI ( Figure 1) in dichloromethane (Table 1, entries 1-6). Catalyst III was the best catalyst for the enantioselective conjugate addition and cyclization cascade (94% ee, Table 1, entry 3). Next, we screened several common solvents including dichloromethane, 1,2-dichloroethane (DCE), chloroform, toluene, ethyl acetate, ethanol, acetonitrile, and acetone (Table 1, entries 3 and 7-13). Chloroform was found to be the optimal solvent in this reaction (Table 1, entry 8). Finally, we lowered the amount of catalyst III to 1 mol %, which compromised the yield and enantioselectivity of the desired product 3a (Table 1, entries 8 and 14-16). However, a further decrease in the amount of catalyst to 0.5 mol % decreased the yield and selectivity (Table 1, entry 17).After determining the optimal reaction conditions, we investigated the substrate scope of of o-QMs 1 with malonitrile 2a in the presence of 1 mol % of catalyst III in dichloromethane at room temperature ( Table 2). The reactions of o-QMs 1a-1e with various substituents in the aryl group yielded the corresponding products 3a-3e in high yields and excellent enantioselectivities (76-88% yields and 89-95% ee). The heteroaryl-substituted o-QM 1f provided desired products 3f with high selectivity (84% yields and 89% ee). To further examine the scope of this ...

show abstract

Section: Optimization Of the Reaction Conditionsmentioning

confidence: 62%

Enantioselective Organocatalytic Michael Addition and Ring Closure Cascade Reaction of o‐Quinone Methides with Nitriles

Park

Jang

Choo

et al. 2020

Bulletin Korean Chem Soc

Self Cite

View full text Add to dashboard Cite

show abstract

“…The reaction adducts with the sulfone moiety are also versatile compounds with wide synthetic applicability by offering access to different functionalities 7. Recently, successful attempts toward the catalytic asymmetric Michael addition of vinyl sulfone or vinyl bis(sulfone) to 3‐aryl‐ or 3‐alkyl‐substituted oxindoles have been reported using organocatalysis, albeit with rather high catalyst loading of about 20 mol % 5c,h. 6f, 8 Among these works, there are limited examples of highly enantioenriched 3,3‐dialkyl‐substituted oxindoles 4l.…”

Section: Optimization[a]mentioning

confidence: 99%

Enantioselective Synthesis of Quaternary Carbon Stereocenters: Addition of 3‐Substituted Oxindoles to Vinyl Sulfone Catalyzed by Pentanidiums

Zong

Chin

et al. 2015

Angew Chem Int Ed

View full text Add to dashboard Cite

A pentanidium-catalyzed highly enantioselective conjugate addition of 3-alkyloxindoles to phenyl vinyl sulfone has been demonstrated. This approach allows the construction of 3,3-dialkyl-substituted oxindole frameworks with high yield and excellent enantioselectivity (up to 99%) under simple phase-transfer conditions. A variety of oxindoles bearing all-carbon quaternary stereogenic centers were obtained in the presence of 0.25 mol% pentanidium. Meanwhile, practicality was illustrated by a gram-scale asymmetric synthesis of two 3,3-dialkyl-substituted oxindoles. The resulting adduct can be smoothly transformed to the natural product analogue in a short synthetic route.

show abstract

“…(Figure ). Due to their biological importance, efforts have been made for the synthesis of both racemic and enantioenriched versions of 3,3-disubstituted oxindoles by relying on several modern techniques. ,,− These include nucleophilic addition to isatins , /isatinimines, oxidative C–H functionalization of N -arylacrylamides, nucleophilic substitution/Michael reaction involving 3-monosubstituted oxindoles as nucleophiles, the decarboxylative addition of β-ketoacids to isatylidene malononitriles/3-haloisatins promoted by several transition-metal catalysts and organocatalysts. Alternatively, an efficient access to C3-quaternary 2-oxindole frameworks was also achieved via an allylic substitution of MBH carbonates of isatins with several C/N/S-nucleophiles such as α,α-dicyanoolefins, γ-butenolide, nitroalkanes, 3,5-dimethyl-4-nitroisoxazole, CbzNHOTBS, and alkylthiols in the presence of Lewis-bases as developed independently by Chen and other groups (Scheme a).…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis of 3,3-Disubstituted Oxindoles and Spirooxindoles via Allylic Alkylation of Morita–Baylis–Hillman Carbonates of Isatins with Cyclic Sulfamidate Imines Catalyzed by DABCO

et al. 2018

View full text Add to dashboard Cite

An efficient, organocatalytic, and ecofriendly method has been developed for the quick construction of a wide array of 3,3-disubstituted oxindoles in good to excellent yields and diastereomeric ratio (up to ≤96:4) with excellent functional group tolerance via an allylic alkylation reaction of cyclic sulfamidate imines with a number of MBH carbonates of isatins in 2-MeTHF as an environmentally benign solvent at room temperature using 5 mol % of DABCO. Furthermore, a metal-free-based one-shot synthesis of a medicinally promising polycyclic spirooxindole with an all-carbon spirocenter has been achieved with outstanding dr value (up to ≤99:1).

show abstract

Enantioselective Michael Addition of 3-Aryl-Substituted Oxindoles to Methyl Vinyl Ketone Catalyzed by a Binaphthyl-Modified Bifunctional Organocatalyst

Cited by 29 publications

References 74 publications

Enantioselective Organocatalytic Michael Addition and Ring Closure Cascade Reaction of o‐Quinone Methides with Nitriles

Enantioselective Organocatalytic Michael Addition and Ring Closure Cascade Reaction of o‐Quinone Methides with Nitriles

Enantioselective Synthesis of Quaternary Carbon Stereocenters: Addition of 3‐Substituted Oxindoles to Vinyl Sulfone Catalyzed by Pentanidiums

Stereoselective Synthesis of 3,3-Disubstituted Oxindoles and Spirooxindoles via Allylic Alkylation of Morita–Baylis–Hillman Carbonates of Isatins with Cyclic Sulfamidate Imines Catalyzed by DABCO

Contact Info

Product

Resources

About