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This article discusses a study on the synthesis of (2-Nitro-1-AfAlemphenylethyl)malononitriles through a reaction called Michael addition. The researchers optimized the reaction conditions and demonstrated its feasibility using different substances. They also explored the possibility of achieving asymmetric induction in the reaction by using a specific catalyst. The results show promise for the synthesis of (2-Nitro-1-AfAlemphenylethyl)malononitriles as precursors for various compounds with potential biological activities. The authors also mention ongoing research to explore the potential applications of these adducts in the synthesis of chiral β-amino acids. [Extracted from the article]

Keywords: N-heterocyclic carbene; regioselective addition; allene; organocatalysis; plant protection EN N-heterocyclic carbene regioselective addition allene organocatalysis plant protection 1997 2000 4 10/09/23 20231024 NES 231024 Graph Allene scaffolds are frequently found in natural products, medicines, and agrichemicals with proven biological activities. Compared with the precatalyst B A b , other aminoindanol-derived NHC catalysts bearing I N i -Ph, [39] I N i -C SB 6 sb F SB 5 sb , [40] and I N i -C SB 6 sb H SB 2 sb Cl SB 3 sb [41] (C SB 6 sb H SB 2 sb Cl SB 3 sb = 1,3,5-trichlorophenyl) gave the target product B 3a b in lower yields and diastereoselectivities (e.g., entries 2-4). Although impressive success has been achieved in the construction of allene frameworks, [23] the development of highly efficient and regioselective methods for quick synthesis of allene derivatives is still challenging. A nucleophilic addition of ROH to intermediate B III b provides the allene product B 3a b , with the regeneration of NHC catalyst for additional catalytic cycles. [Extracted from the article]

[5] Many organocatalysts, such as chiral quaternary ammonium salts (Maruoka catalysts), [14] chiral phosphoric acid catalysts (Akiyama-Terada catalysts), [15][16] chiral cyclic secondary amine catalysts (Hayashi-Jørgensen catalysts), [17] and a chiral aminothiourea catalyst (the Takemoto catalyst) [19] have been developed, and their efficiencies have been well showcased in various asymmetric reactions. Motivated by these circumstances, we investigated the substituent effect with a focus on the electronic effects of the aromatic rings in butterfly-type catalysts, and we found that a 3,5-bis(trifluoromethyl)phenyl-group-substituted catalyst exhibited superior catalytic performance compared with the well-known Takemoto catalyst in some asymmetric reactions. Keywords: thiourea catalysis; asymmetric catalysis; diarylmethylamines; organocatalysis; Michael reaction EN thiourea catalysis asymmetric catalysis diarylmethylamines organocatalysis Michael reaction 1899 1904 6 09/15/23 20231004 NES 231004 Graph The pioneering works of the groups of MacMillan [1] and of List and Barbas [3] have triggered interest in the development of organocatalysts, which has evolved into one of the major topics of research in modern synthetic organic chemistry. It is worth noting that its asymmetry-inducing ability was superior to that of the well-known aminothiourea catalyst, the Takemoto catalyst, and this characteristic was observed in various asymmetric reactions. [Extracted from the article]

Although we have previously reported catalytic asymmetric Mukaiyama-Michael reactions that afforded high yields and enantioselectivities [24][25] when an enol silane of a propionate was used therein, neither the enantioselectivity nor the diastereoselectivity could be controlled. Next, the solvent was fixed at a 2:1 mixture of toluene and DCM, and the reactions of B 5 b and B 6 b were examined by using various bisoxazoline ligands B L1 b - B 12 b [29] (Figure 2). The Mukaiyama-Michael reactions of B 5 b with various enol silanes of propionates were studied by using B L3 b in the mixed solvent (2:1 toluene-DCM) (Table 3). [14] However, although there are many reports on catalytic asymmetric Mukaiyama-Michael reactions, [8] there are almost none on successful reactions of the enol silanes of ethyl ketones or propionates with cyclopentenones containing an electron-withdrawing group at the -position. [Extracted from the article]

Enantioselective formal total synthesis of damsin, which was isolated from Compositae Ambrosia maritima L., is described. The highly enantio- and diastereoselective catalytic Mukaiyama–Michael reaction and subsequent highly stereoselective epimerization shorten the synthetic steps. It is also reported that the enolate, which was formed by the reaction of β-keto sulfone with lithium naphthalenide, reacted with methyl cyanoformate to form a quaternary stereogenic center in high yield with high stereoselectivity. This finding extends the synthetic chemistry starting from β-keto sulfones. [ABSTRACT FROM AUTHOR]

Deep learning is widely used in chemistry and can rival human chemists in certain scenarios. Inspired by molecule generation in new drug discovery, we present a deep-learning-based approach to reaction generation with the Trans-VAE model. To examine how exploratory and innovative the model is in reaction generation, we constructed the dataset by time splitting. We used the Michael addition reaction as a generation vehicle and took these reactions reported before a certain date as the training set and explored whether the model could generate reactions that were reported after that date. We took 2010 and 2015 as time points for splitting the reported Michael addition reaction; among the generated reactions, 911 and 487 reactions were applied in the experiments after the respective split time points, accounting for 12.75% and 16.29% of all reported reactions after each time point. The generated results were in line with expectations and a large number of new, chemically feasible, Michael addition reactions were generated, which further demonstrated the ability of the Trans-VAE model to learn reaction rules. Our research provides a reference for the future discovery of novel reactions by using deep learning. [ABSTRACT FROM AUTHOR]

This review is devoted to underpinning the contributions of Indian researchers towards asymmetric organocatalysis. More specifically, a comprehensive compilation of reactions mediated by a wide range of non-covalent catalysis is illustrated. A detailed overview of vividly catalogued asymmetric organic transformations promoted by hydrogen bonding and Brønsted acid catalysis, alongside an assortment of catalysts is provided. Although asymmetric organocatalysis has etched itself in history, we aim to showcase the scientific metamorphosis of Indian research from baby steps to large strides within this field. 1 Introduction 2 Non-Covalent Catalysis and Its Various Activation Modes 3 Hydrogen-Bonding Catalysis 3.1 Urea- and Thiourea-Derived Organocatalysts 3.1.1 Thiourea-Derived Organocatalysts 3.1.2 Urea-Derived Organocatalysts 3.2 Squaramide-Derived Organocatalysts 3.2.1 Michael Reactions 3.2.2 C-Alkylation Reactions 3.2.3 Mannich Reactions 3.2.4 [3+2] Cycloaddition Reactions 3.3 Cinchona-Alkaloid-Derived Organocatalysts 3.3.1 Michael Reactions 3.3.2 Aldol Reactions 3.3.3 Friedel–Crafts Reactions 3.3.4 Vinylogous Alkylation of 4-Methylcoumarins 3.3.5 C-Sulfenylation Reactions 3.3.6 Peroxyhemiacetalisation of Isochromans 3.3.7 Diels–Alder Reactions 3.3.8 Cycloaddition Reactions 3.3.9 Morita–Baylis–Hilman Reactions 4 Brønsted Acid Derived Organocatalysts 4.1 Chiral Phosphoric Acid Catalysis 4.1.1 Diels–Alder Reactions 4.1.2 Addition of Ketimines 4.1.3 Annulation of Acyclic Enecarbamates 5 Conclusion [ABSTRACT FROM AUTHOR]

Ni(II) complex of the Schiff base of the chiral auxiliary (S)-2- N -(N ′-benzylprolyl)aminobenzophenone (BPB) and dehydroalanine as the initial complex in the addition reaction was investigated. The obtained four new derivatives of α-alanine were investigated as inhibitors of aldose reductase. Only one of them: (S)-2-amino-3-[(4-methylbenzyl)amino]propanoic acid showed activity. It becomes a reason for studying the patterns of biological activity of the structure of α-amino acids. The results of docking analysis indicated that (S)-2-amino-3-[(4-methylbenzyl)amino]propanoic acid demonstrated the ability to form bonds with different functional groups of the enzyme which let us assume that some amino acids of nonfunctional groups, such as Trp20 of ALR2, can play a key role in inhibitor–enzyme interactions. [ABSTRACT FROM AUTHOR]

An asymmetric Michael reaction of malononitrile and α,β-unsaturated aldehydes catalyzed by a diarylprolinol silyl ether was developed. Michael products were obtained in good yields and with excellent enantioselectivities without the formation of overreaction products. As a malononitrile moiety can be transformed into an alkoxy or amino carbonyl moiety by oxidative transformation, α-chiral esters or amides with all-carbon quaternary centers can be synthesized with excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

A well-known squaramide-cinchonine organocatalyst was immobilized in a controlled way onto three types of commercial porous glass beads EziG™ (EziG OPAL, EziG Amber, and EziG Coral) and applied in asymmetric Michael reactions. The performance of the immobilized catalysts was evaluated under batch and continuous-flow conditions, showing promising results in both approaches. In batch reactions, 0.8 and 1.6 mol% of the immobilized cinchonine-squaramide provided the products with excellent yields (up to 99%) and enantioselectivities (up to 99% ee). These excellent results were also verified in the case of continuous-flow reactions, where also 0.8 and 1.6 mol% of the catalyst immobilized onto the glass beads afforded the product with extraordinary yields (up to 99%) and very high enantioselectivities (up to 97% ee). The immobilized catalysts could be recycled (up to seven cycles) using both approaches. [ABSTRACT FROM AUTHOR]

A chiral N -2,3,4,5-tetrafluoro-6-iodobenzyl- N -sulfonyl -aminomethylpyrrolidine tetrafluoroacetic acid salt was designed as an -iodinated enamine organocatalyst for the enantioselective -Michael/hemiaminal formation cascade reaction of α,β-unsaturated -iminoindoles with aldehydes. The use of this iodinated enamine -catalyst furnished anti -α-carbolinol derivatives in high yields and high stereoselectivities. [ABSTRACT FROM AUTHOR]

A mild synthesis of 3,5-disubstituted nitrobenzenes from readily available 3-formylchromones is reported. The developed methodology follows a cascade process, promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene. The proposed mechanism involves an initial Michael addition of nitromethane at C-2 of a 3-formylchromone. The resultant intermediate undergoes another Michael reaction with a second 3-formylchromone molecule. After ring closure through intramolecular cyclization, the aromatization is completed by deformylation, affording the 3,5-disubstituted nitrobenzenes in 52–86% yield. The reported method produces three new C–C bonds in a simple and straightforward manner, and it is consistent with gram-scale synthesis. [ABSTRACT FROM AUTHOR]

In the reactions of simple starting materials, precise catalytic control of the stereochemical outcome (enantio- and diastereoselectivity), as well as chemoselectivity and regioselectivity is an efficient approach to increase molecular complexity with minimal use of protecting groups. Here, we introduce our ongoing studies on asymmetric catalytic reactions using α-keto esters as pronucleophiles or formal 1,3-dipolarophiles. Capitalizing on the high tunability of our late transition-metal complexes with a suitable basic counteranion, we have established a range of multiselective catalytic protocols starting from α-keto esters to provide a wide variety of stereochemically complex molecules incorporating adjacent stereocenters. 1 Introduction 2 Catalytic Asymmetric Monofluorination with NSFI 3 Catalytic Asymmetric Michael Reaction with Nitroolefins 4 Catalytic Asymmetric [3+2] Cycloaddition with (E)-Nitrones 5 Catalytic Asymmetric [3+2] Cycloaddition with Nitrile Oxides 6 Summary [ABSTRACT FROM AUTHOR]

An efficient synthetic route to install chiral 1,3-dimethyl units through a double Michael reaction of crotonaldehyde and nitromethane catalyzed by diphenylprolinol silyl ether is developed. Either 1,3- syn - or 1,3- anti -dimethyl units are obtained selectively depending on the enantiomer of the diphenylprolinol silyl ether catalyst used. The side chain of pneumocandin B0 is synthesized enantioselectively by using the present method as a key step. [ABSTRACT FROM AUTHOR]

The first total synthesis of kukoamine B bimesylate was completed from 1,4-diaminobutane dihydrochloride in 12 steps with a 11.4% overall yield, and all the steps could be carried out at a kilogram scale. The cyano groups were used as the precursor of amino groups to avoid the competitive reaction delicately. The aza-Michael addition reaction, amidation and hydrogenation of the cyano group sequence was streamlined as a general approach towards the synthesis of polyamine structures. [ABSTRACT FROM AUTHOR]

A novel series of 9,10-dihydro-3 H -10a-azaphenanthrene-2,4-dicarbonitrile derivatives that contain a bridgehead nitrogen were prepared by a three-component reaction of aldehydes, 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile, and 3-aminocrotononitrile in acetic acid. [ABSTRACT FROM AUTHOR]

A convenient Michael addition/cyclization sequence of alkyl isocyanide–acetylenic ester zwitterionic adducts with various pyrazolone derivatives, leading to the formation of dialkyl 6-(alkylamino)-1-methyl-4-oxo-3-phenyl-9-aryl-2,3-diazaspiro[4.4]nona-1,6,8-triene-7,8-dicarboxylates in moderate to good yields, is described. The structure of the target compounds was confirmed by an X-ray diffraction study. [ABSTRACT FROM AUTHOR]

The Michael addition of dehydroalanine-activated ester in situ generated from N,N-phthaloyl-serine with o-phenylenediamine followed by cyclization has been established under mild conditions, which afforded 3-phthalimido-1,5-benzodiazepine-2-one derivatives in moderate to good yields. [ABSTRACT FROM AUTHOR]

Extending earlier studies on iodine catalysis, experimental investigations show that various halogen-bond donors can also be employed to accelerate the Michael addition between trans-crotonophenone and indole. Solvent as well as counteranion effects have been analyzed, and kinetic and computational investigations provide additional insights into the mode of activation. [ABSTRACT FROM AUTHOR]

An amine-promoted (4+3) annulation of δ-acetoxy allenoate with o-diaminobenzene is reported, providing a facile access to 1,5-benzodiazepine. This method features wide reaction scope, mild conditions, and readily available starting materials. The cascade reaction involves aza-Michael addition of o-diaminobenzene to allenoate, elimination of acetate group, and subsequent 1,6-aza-Michael addition. [ABSTRACT FROM AUTHOR]

Thia-Michael addition of thiophenol to α,α'-di[(E)-benzylidene] alkanones of both cyclic (six-membered) and acyclic varieties using anhydrous K2CO3 or amberlyst-15 as catalyst has been found to be highly diastereoselective at 15 °C. A one-pot protocol was developed for such reactions by a tandem aldol-thia-Michael process. The stereochemistry of the products was confirmed by X-ray crystallographic studies and in all cases formation of a meso product was observed. [ABSTRACT FROM AUTHOR]

We developed an enantioselective organocascade Michael/ Henry reaction in the presence of a bifunctional organocatalyst to construct chiral polyfunctionalized 3,4-dihydro-2H-thiopyrano[2,3- b]quinolines. The resulting optically active products with three contiguous stereocenters, one quaternary and two tertiary, were obtained in moderate to good yields and with good to excellent enantioselectivities. Remarkably, the resulting products were readily converted into polyfunctionalized optically active furo[2',3':4,5]thiopyrano[2,3- b]quinoline, 3,4-dihydro-2H-thiopyrano[2,3-b]quinoline 1-oxide and 2,3-dihydro-4H-thiopyrano[2,3-b]quinolin-4-one derivatives. [ABSTRACT FROM AUTHOR]

An organocatalytic, asymmetric, double-Michael strategy has been developed employing trans-α-cyano-α,β-unsaturated ketones for the synthesis of pentasubstituted tetrahydrothiopyrans bearing a quaternary center. A proline-derived bifunctional thiourea was found to be the most effective catalyst for this reaction. With 10 mol% of catalyst, good yields and good to high diastereomeric ratios, as well as excellent enantioselectivities, were obtained with a variety of tetrahydrothiopyrans under mild reaction conditions. [ABSTRACT FROM AUTHOR]

A novel metal-free and base-mediated method to display the donor ability of 1,2,3-triazoles for the synthesis of 2,4-disubstituted 1,2,3-triazoles has been developed. A DABCO-promoted aza-Michael addition of 4-aryl NH-1,2,3-triazoles to α,β-unsaturated ketones (chalcones) is presented. The reactions proceeded with complete regiospecificity in a 3:1 mixture of acetonitrile and methanol at 85 °C to provide 2,4-disubstituted 1,2,3-triazoles as Michael adducts, and the addition products 1,3-diaryl-(4-aryl-2H-1,2,3-triazol-2-yl)propan-1-ones were isolated in high yields. [ABSTRACT FROM AUTHOR]

From N-acryloyl indoles, ten examples of 1,2-annulated indole products were generated in a one-pot procedure via a Michael addition and radical cyclization mediated by Mn(OAc)3. [ABSTRACT FROM AUTHOR]

The Lycopodium alkaloids possess a rich history that has captured the attention of synthetic chemists across the globe. This large family consists of over 250 known natural products with diverse structural features and noteworthy biological activity. Herein, we interweave the synthetic accomplishments by others in the field with our own unified strategy to accessing multiple subfamilies of the Lycopodium alkaloids. This discussion includes lycopodine, the C10-hydroxy Lycopodium alkaloids (10-hydroxylycopodine, deacetylpaniculine and paniculine), pelletierine, cermizine D, fastigiatine, himeradine A, clavolonine and 7-hydroxylycopodine. A unifying feature of much of the work discussed within this account is the use of intramolecular Michael additions to construct key ring systems within the Lycopodium alkaloids. Examples include the use of an intramolecular keto-sulfone Michael reaction and an intramolecular heteroatom Michael reaction. 1 General Background on Lycopodium Alkaloids 2 Development of a Strategy for Lycopodium Alkaloids 2.1 Generalized Strategy 2.2 Known Syntheses of C10-Functionalized Lycopodium Alkaloids 3 Quinolizidine-Type Alkaloids 3.1 Background 3.2 Development of the Heteroatom Michael Reaction 3.3 Synthesis of the Core Lycopodine Building Block: Pelletierine 3.4 Total Synthesis of Cermizine D 3.5 Synthesis of the Eastern Half of Himeradine A 4 Lycopodine-Type Alkaloids 4.1 Total Syntheses of Lycopodine 4.1.1 Earlier Racemic Syntheses 4.1.2 Approach Toward the Tricyclic Skeleton of Lycopodine: Intramolecular Mannich 4.1.3 Enantioselective Total Syntheses of Lycopodine 4.2 Total Syntheses of Clavolonine (8-Hydroxylycopodine) 4.3 Total Synthesis of 7-Hydroxylycopodine 4.4 Synthetic Route for 10-Hydroxy Lycopodium Alkaloids 4.4.1 Background 4.4.2 Total Syntheses 4.4.3 Impact of the C10-Stereochemistry 5 Conclusion [ABSTRACT FROM AUTHOR]

A Michael-induced ring-closure (MIRC) strategy allowing the synthesis of 2-substituted aziridine-2-carboxylic esters is presented. A broad spectrum of nucleophiles can be applied, leading to large diversity of products which can be subjected to further structural modifications. Diastereoselective ring closure is observed in the case of chiral substrates. [ABSTRACT FROM AUTHOR]

3-Alkylindoles on reaction with a cyclohexa-2,4-dien-1-one catalyzed by BF3·OEt2 gave the corresponding 3-alkyl-3-arylindolenines in high yields through a tandem Michael addition/aromatization sequence. In the presence of HCl, these indolenine derivatives underwent a facile Plancher-type C-3 to C-2 aryl rearrangement to deliver the corresponding 2-arylindoles. [ABSTRACT FROM AUTHOR]

Indole is one of the utmost important heterocycles as it is an essential nucleus of many pharmaceutical compounds. Its aza-Michael reaction, however, is underdeveloped because of the moiety's inherent characteristics. Here, a potassium hydroxide catalysed intermolecular aza-Michael reaction of 3-cyanoindole with aromatic enones is described. A variety of chalcone derivatives are well tolerated and afford the corresponding N-adducts in moderate to high yields. The use of a cheap catalyst, low catalyst loading, mild reaction temperature, and good substrate tolerance make this procedure a direct and facile method for the preparation of N1-functionalized indoles. [ABSTRACT FROM AUTHOR]

A convenient method for synthesizing 3-amino-1,5-benzodiazepine-2-one via the Michael addition reaction of o-phenylenediamine with dehydroalanine ester derivatives, followed by cyclization, was developed. This simple method was used to obtain a variety of N-substituted 3-amino-1,5-benzodiazepine-2-ones in one pot with good yields. [ABSTRACT FROM AUTHOR]

Starting from easily accessible propargylic fluorides an intramolecular oxa-Michael addition affords, in good yields, new gem-difluorodihydrobenzofurans bearing an electrophilic double bond in position 2. On these intermediates nucleophilic additions and Diels-Alder reactions have been performed affording functionalized fluorinated dihydrobenzofurans. On the other hand, Pd-catalyzed defluorinations give the corresponding fluorine containing benzofurans. [ABSTRACT FROM AUTHOR]

Lithium 3,3'-chlorobinaphtholate was found to catalyze the enantioselective Michael addition of a malonic ester to a maleic ester. High enantioselectivities (>90% ee) were observed, especially in the reactions of 2-alkylmalonic esters and maleic esters. [ABSTRACT FROM AUTHOR]

We report an asymmetric sulfa-Michael reaction of α,β-unsaturated amides and esters using a chiral N-heterocyclic carbene as the HOMO-raising organocatalyst. We discovered an interesting correlation between 13C NMR shifts of substrates and ee of their products. More electron-deficient Michael acceptors afforded higher enantioselectivity. [ABSTRACT FROM AUTHOR]

A facile and efficient method for the synthesis of six-membered enol carbocyclic compounds was realized by intermolecular cyclization reaction of 3-aryllidenepentane-2,4-diones with t-BuOK in CH2Cl2. The reaction is conducted under mild conditions and shows good functional group tolerance. [ABSTRACT FROM AUTHOR]

The Lewis acid catalyzed intramolecular conjugate addition of 3',4',5'-trimethoxybiphenyl-2-propenones give the corresponding 8,9,10-trimethoxydibenzocycloheptanones in good yields. A case of a conjugate addition-cation rearrangement of a 2',3',4'-trimethoxybiphenyl- 2-propenone to give the same ring system is also reported. The dibenzocycloheptanones may be converted readily into the 8,9,10-trimethoxy- substituted allocolchicinoids in highly enantioenriched form. [ABSTRACT FROM AUTHOR]

The enantioselective Michael addition reaction of α-aryl-substituted lactams with electron-deficient olefins was efficiently catalyzed using chiral quaternary ammonium salts derived from cinchona alkaloids. This method was highly useful for the construction of an all-carbon-substituted quaternary carbon stereogenic center at the α-position of lactams in good to high yields and with good enantiomeric excess and could be applied to the short synthesis of (+)-mesembrine. [ABSTRACT FROM AUTHOR]