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This article explores the synthesis and characterization of chejuenolides, a group of natural products with potential medicinal applications. The authors conducted total synthesis of chejuenolide C and identified it in a newly discovered strain of bacteria. They also investigated the stereochemistry involved in the macrocyclization process and found that the configuration at C13 has a significant impact on the stereochemistry of the product. The authors hope that their research will inspire further studies in biomimetic synthesis. [Extracted from the article]

This article discusses the synthesis of a novel amino triflamide catalyst and its application in enamine catalysis. The catalyst is derived from commercially available 1-nitropyrene and has a unique reactivity and selectivity. The synthesis of the catalyst involves several steps, but it offers a more efficient alternative to previously developed catalysts. The article also presents the results of several asymmetric reactions using the newly synthesized catalyst, demonstrating its utility in synthetic organic chemistry. [Extracted from the article]

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]

Most chiral secondary amine catalysts are usually synthesized from chiral amino acids and their derivatives. On the other hand, amine catalysts based on a binaphthyl backbone have previously been developed, and show unique chemo- and stereoselectivity in several asymmetric reactions. However, in spite of their utility, the applications of binaphthyl-based amines in asymmetric reactions are still rare due to their synthetic inefficiency. In this context, we have designed amine catalysts possessing a phenylcyclopropane scaffold as a novel chiral motif. These novel catalysts can be synthesized easily and construct a similar chiral environment to that of binaphthyl-based amine catalysts. In addition, a phenylcyclopropane-based amino sulfonamide is found to be an effective catalyst for syn -selective Mannich reactions and conjugate additions using alkynyl Z -ketimines. 1 Introduction 2 Design and Synthesis of Novel Chiral Secondary Amine Catalysts 3 Performance Evaluation of Phenylcyclopropane-Based Amine Catalysts 4 Development of Asymmetric Reactions Catalyzed by a Novel Chiral Amino Sulfonamide 5 Conclusions [ABSTRACT FROM AUTHOR]

The asymmetric Mannich reaction of 3-fluorooxindoles and α-amidosulfones catalyzed by a chiral urea catalyst derived from quinine in presence of K3 PO4 was developed. Through the asymmetric reaction, a series of α-fluoro-β-amino-oxindoles, containing a tertiary carbon stereocenter, could be obtained in high yields (up to 95%) with high enantioselectivity (95%) and diastereoselectivity (>99:1). Such α-fluoro-β-amino-oxindole compounds are expected to become candidates in the field of medicine. [ABSTRACT FROM AUTHOR]

Chiral phase-transfer catalysts derived from tert -leucine were synthesized and used in the asymmetric synthesis of 4-azaindoline derivatives. By this method, both enantiomers of the corresponding products were obtained in excellent yield (up to 99%) with high enantio-selectivities (up to 91% ee) and diastereoselectivities (up to >99: 1 dr). [ABSTRACT FROM AUTHOR]

A multioperation, continuous-flow platform for the synthesis of tramadol, ranging from gram to decagram quantities, is described. The platform is segmented into two halves allowing for a single operator to modulate between preparation of the intermediate by Mannich addition or complete the fully concatenated synthesis. All purification operations are incorporated in-line for the Mannich reaction. 'Flash' reactivity between meta -methoxyphenyl magnesium bromide and the Mannich product was controlled with a static helical mixer and tested with a combination of flow and batch-based and factorial evaluations. These efforts culminated in a rapid production rate of tramadol (13.7 g°h–1) sustained over 56 reactor volumes. A comparison of process metrics including E-Factor, production rate, and space-time yield are used to contextualize the developed platform with respect to established engineering and synthetic methods for making tramadol. [ABSTRACT FROM AUTHOR]

β-Alkoxycarbonyl-γ-lactams and γ-alkoxycarbonyl-δ-lactams were synthesized via a conjugate alkylation/Mannich reaction/lactamization tandem reaction of unsaturated dicarboxylates with diethyl zinc and aldimines. The high yield, the ready availability of the reagents, and especially the high diastereoselectivity are promising characteristics of the approach that allows access to functionalized lactams. [ABSTRACT FROM AUTHOR]

PhosphoiminoBINOL-Pd2 (OAc)2 complex catalyzed asymmetric Mannich reaction of N -Boc imines with alkyl malononitriles, with assistance of Zn(OAc)2 gave chiral amines with adjacent all-carbon quaternary carbon centers in up to 99% yield with 94% ee. [ABSTRACT FROM AUTHOR]

An α-CF3 amide underwent direct asymmetric Mannich-type reaction to isatin imines in the presence of a chiral catalyst comprising a soft Lewis acid Cu(I), a chiral bisphosphine ligand, and Barton's base. The Mannich adduct was converted in one step into a unique tricycle bearing a trifluoromethylated chiral center and an α-tertiary amine moiety. [ABSTRACT FROM AUTHOR]

A new type of optically pure primary amino aromatic Tf-amide organocatalyst can be easily prepared from 8-amino-1-tetralone, and its chemical behavior was investigated in the context of asymmetric aldol and Mannich reactions. Most notably, the asymmetric aldol reaction proceeded smoothly in brine. [ABSTRACT FROM AUTHOR]

Chiral butenolides were synthesized by the enantioselective vinylogous Mannich reaction. Chiral (VAPOL)-type imidodiphosphoric acids are efficient catalysts for the asymmetric vinylogous Mannich (AVM) reaction of aldimines and trimethylsiloxyfuran in toluene. Under the optimized conditions, a series of butenolides were obtained with high yields (up to 98%) and enantioselectivities (up to 97% ee) as well as excellent diastereoselectivities (up to 99:1 dr). [ABSTRACT FROM AUTHOR]

A series of both enantiomers of chiral β-amino acid ester derivatives containing a 4-(piperidin-1-yl)pyrimidine moiety was prepared in high yield and excellent enantioselectivity excess (up to >99% enantiomeric excess) using a chiral cinchona alkaloid thiourea catalyst under one-pot solvent-free conditions. Antiviral bioassay experimental results showed that some of the chiral products exhibited higher antiviral activities against tobacco mosaic virus (TMV) in vivo than the commercial antiviral agent ningnanmycin. [ABSTRACT FROM AUTHOR]

Sugar-based primary amines have been employed as organocatalysts for the direct asymmetric Mannich reaction. By catalystscreening experiments, we observed that catalysts bearing a hydroxy function at C-3 actively participated in the reaction, possibly through hydrogen bonding with the imine generated in situ, to provide β-amino carbonyl compounds with better diastereoselectivity and enantioselectivity. All the products were obtained in good to excellent enantiomeric excess. [ABSTRACT FROM AUTHOR]

An efficient enantioselective Mannich reaction of N-protected α-sulfones with β-benzenesulfonyl phosphonates was developed by using a chiral cinchona alkaloid-derived thiourea as a catalyst. This method was used to obtain a series of chiral α-sulfonyl-β-aminophosphonates in yields of up to 96% with 89:11 dr and 88% ee. These compounds were further transformed into β-aminophosphonates or chiral azetidines with various functional groups by a Horner--Wadsworth--Emmons/aza-Michael addition reaction sequence. [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]

Ph3PAuOTf was identified as a powerful catalyst for the Mukaiyama-Mannich reaction of fluorinated silyl enol ethers with α-amino sulfones. This provides ready access to β-amino α-fluorinated ketones in good to excellent yields. [ABSTRACT FROM AUTHOR]

A facile and an efficient direct vinylogous aldol/Mannich reaction of furan-2(3H)-one with isatins or isatinimines has been developed by using DABCO as an organocatalyst at room temperature. The synthetic protocol is atom-economical and provides easy access to a variety of oxindole derivatives. This is the first example of a direct vinylogous aldol/Mannich reaction between isatins/isatinimines and furan2(3H)-one to afford vinylogous aldol adducts. The substrate scope of the protocol is briefly discussed. [ABSTRACT FROM AUTHOR]

1-Alkylprolines undergo decarbonylative reactions with oxalyl chloride and subsequent Mannich reactions with nonactivated C-H nucleophiles to give 2-substituted pyrrolidines as Mannich adducts. We showed that 1-alkyl-1-pyrrolinium compounds are the reactive intermediates formed by the decarbonylative reactions of 1-alkylprolines. Our results also confirmed that an azomethine ylide, although unreactive toward the Mannich reaction and not involved in the decarbonylative Mannich reaction, can be generated by deprotonation of the corresponding 1-alkyl-1-pyrrolinium compound under mild conditions. [ABSTRACT FROM AUTHOR]

A new, sequential proline-catalyzed approach to the synthesis of (+)-L-733,060 and (+)-T-2328 in high optical purity (93% ee) is described starting from phenyl N-Boc imine. The strategy involves prolinecatalyzed Mannich reaction of an arylimine with acetaldehyde followed by α-aminoxylation/Wittig olefination in a sequential fashion as the key steps. [ABSTRACT FROM AUTHOR]

Synthetic studies on acochlearine are described. The pentacyclic A/B/C/E/F ring system of acochlearine was constructed from a bicyclic enone via chemoselective reductive amination, one-pot bromination-intramolecular Mannich reaction cascade, and 6n-electrocyclization. [ABSTRACT FROM AUTHOR]

The C-arylation of Mannich base is used to obtain a series of new arylmethylene resorcinarene derivatives. Initially, aminomethyl derivative as the intermediate is formed in the Mannich reaction of resorcinarene with iminodiacetic acid. Next, activated aromatic rings act as a nucleophile in the reaction with this Mannich base and the arylmethylene derivatives of resorcinarene are prepared. The mixture of isomeric products is obtained for monosubstituted phenyl rings. Reaction with a suitably substituted phenyl ring gives one main product in good yields. [ABSTRACT FROM AUTHOR]

The enantioselective phospha-Mannich reaction of diethyl phosphite to unactivated N-DPP-protected ketimines catalyzed by a bifunctional iminophosphorane (BIMP) superbase organocatalyst is described. The reaction is applicable to ketimines bearing electron-rich and electron-poor aryl substituents and occurs with excellent yields and moderate enantioselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Conjugate addition of an alkyl group to a series of 2-iminonitrostyrenes and then addition of trifluoroacetic acid initiates a nitro-Mannich cyclisation to give cis, cis-2,3,4-substituted tetrahydroquinolines in good yield and high diastereoselectivity. [ABSTRACT FROM AUTHOR]

A catalytic enantioselective Mannich-type reaction of a cyclohexanone- derived alkenyl trichloroacetate with isatin imines was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-tert-butylphenyl group at 3- and 3'-positions as the chiral precatalyst in the presence of sodium methoxide, sodium iodide, and methanol. Optically active 3-alkylated 3-amino-2-oxindoles having up to 90% enantiomeric excess were diastereoselectively obtained in high yields under the influence of the in situ generated chiral tin iodide methoxide. [ABSTRACT FROM AUTHOR]

The article discusses a study concerning a method developed by the group of Professor Motomu Kanai at the University of Tokyo in Japan for generating carboxylic acid derived enolates under mild conditions for Mannich-type reactions. It highlights the two key aspects involved in the boron catalysis, the chemoselectivity and enantioselectivity. The significance of developing a method for structural modification and homologation of carboxylic acid derivatives is noted.

An efficient bifunctional thiourea catalyzed asymmetric Mannich reaction with trifluoromethyl aldimine as trifluoromethyl building block was achieved to give the products in good diastereoselectivity and enantioselectivity. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed Heck-type coupling method between arenes and ketone Mannich bases via C-N cleavage to synthesize chalcones is reported. This protocol offers good yields and tolerates a broad range of functional groups. Based on the extensive experimental data, we propose a plausible coulping mechanism. [ABSTRACT FROM AUTHOR]

The Mannich reaction between pyrroles or indoles and Eschenmoser's salt (dimethylmethylideneammonium iodide) forms N,N-dimethylamino-methylated derivatives in good to excellent yields. The reaction is highly regioselective, and for pyrroles both 2- and 3-substituted derivatives could be obtained. The N,N-dimethylaminomethylpyrroles and indoles underwent substitution with pyrrole under microwave irradiation, affording the appropriate dipyrromethanes, Nconfused, and indolo-dipyrromethanes in moderate to excellent overall yield. [ABSTRACT FROM AUTHOR]

An efficient asymmetric vinylogous Mannich (AVM) addition reaction of 3-alkenyl-2-oxindoles to α-fluoroalkyl aldimines has been developed. This reaction provided various optical active α-alkylidene- δ-amino-δ-fluoroalkyl oxindoles in excellent yields, complete γ-site regioselectivity, and excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

β-Carboalkoxy-γ-lactams were synthesized in high yields via copper-catalyzed three-component reactions of α,β-unsaturated dicarboxylate esters, aldimines, and a silane. The reaction proceeds in a tandem manner via conjugate reduction, Mannich reaction, and a subsequent lactamization. The method is attractive with regard to the flexible combination of easily available reactants, the mild conditions, and the high yields. It provides a concise synthetic route to functionalized lactams with a β-ester group. [ABSTRACT FROM AUTHOR]

Switching enantioface selection of imines in the metalcatalyzed nitro-Mannich reaction was accomplished with the same enantiomer of diamine-derived bis(imidazolidine)pyridine (PyBidine) ligand. The (S,S)-PyBidine-CoCl2 complex catalyzed the nitro-Mannich reaction of N-Ts imines to give S-enriched adducts, while the Ni(OAc)2 complex using the same ligand catalyzed the nitro-Mannich reaction of N-Boc imines in an R-stereoselective manner. [ABSTRACT FROM AUTHOR]

In our search for new easily accessible analogues based on the natural product podophyllotoxin, we synthesized 1-aza-4-deoxypicropodophyllotoxin in good overall yield and excellent enantioselectivity. The synthesis was centered around a direct asymmetric Mannich reaction using D-proline as the key step for introduction of the chiral centres. Our synthesis of 1-aza-4-deoxypodophyllotoxin was hindered through the increased instability towards epimerization of the C2 position. We did, however, synthesized a new scaffold based on the opened lactone analogue. [ABSTRACT FROM AUTHOR]

A highly efficient diastereoselective Mannich reaction has been carried out in water using a catalytic amount of β-cyclodextrin as a chiral host in the presence of acetic acid to give the corresponding β-aminoketones (Mannich bases) with good yield (up to 98%) and excellent diastereomeric excess (up to >99%). This ­Brønsted acid–chiral cyclodextrin composite catalyzed reaction proceeds in a syn-selective manner with 98:2 syn/anti selectivity when propiophenone is used as the ketone moiety and in an anti-­selective manner with 100:0 (anti/syn) selectivity when cyclohexanone is used. [ABSTRACT FROM AUTHOR]

A new efficient method using the Mannich three-component reaction in one pot to synthesize [1+2+1]- and [2+4+2]-macrocyclic compounds possessing a propargylamine backbone was reported. Interestingly, 1,4-diazepane as a multiuse reagent played the part of a substrate to participate in the Mannich reaction and acted as a base to promote the Eglinton-Glaser dimerizations in the coordination processes simultaneously via a one-pot procedure. The target macrocycles were obtained in good yields. [ABSTRACT FROM AUTHOR]

The asymmetric nitro-Mannich reactions of nitroalkanes and in situ generated N-Boc-imines were achieved with a new type of thiourea-guanidine bifunctional organocatalyst. The novel transformations exhibited good diastereoselectivities, and the adducts bearing adjacent chiral centers were generally obtained in moderate to high enantioselectivities (up to 94% ee). This reaction provides a concise and alternative route converting readily accessible and stable N-carbamate amido sulfones into optically active 1,2-diamino compounds. [ABSTRACT FROM AUTHOR]

Mannich-type reactions with nitrones, oximes, and hydrazones provide efficient approaches to β-amino carbonyl derivatives with nitrogen functionality existing in an intermediate oxidation state, as in the cases of hydroxylamine and hydrazine derivatives. By employing chiral substrates and catalysts enantiomerically pure substances can be prepared by using these processes. 1 Introduction 2 Mannich-Type Reactions with Nitrones 2.1 Metal Enolates 2.2 Silyl Ketene Acetals 3 Mannich-Type Reactions with Oximes 4 Mannich-Type Reactions with Hydrazones 5 Concluding Remarks [ABSTRACT FROM AUTHOR]

2-Aryl-3H-indol-3-ones reacted with aldehydes or ketones in the presence of L-proline as a catalyst to give the corresponding aza-quaternary carbon addition product in good yield with moderate to excellent regioselectivity and enantioselectivity. The system was applied to the reaction of 2-(2-bromo-phenyl)-3H-indol-3-one and acetaldehyde to give 2-[2-(2-bromophenyl)-3-oxoindolin-2-yl]acetaldehyde, which is a precursor for the synthesis of some alkaloids such as hinckdentine A. [ABSTRACT FROM AUTHOR]

An efficient one-pot synthesis of hydroxynaphthyl-substituted glycine derivatives from 2- or 1-naphthol, glyoxylic acid, and benzyl carbamate via a modified Mannich reaction is described. The enantiomers were successfully separated on analytical and semipreparative HPLC columns. Their absolute configurations were determined by CD analysis supported by TDDFT CD calculations. [ABSTRACT FROM AUTHOR]

The highly enantioselective direct Mannich protocol employing fluoroacetone, P-anisidine, and aldehydes catalyzed by 4-siloxyproline was developed, allowing efficient access for pharmaceutically important fluorinated ?-amino ketones. On the basis of DFT calculations and mechanistic probes, the origin of an unusual reversal of regioselectivity was unraveled. [ABSTRACT FROM AUTHOR]

Asymmetric calcium-catalyzed direct Mannich reactions of 1,3-dicarbonyl compounds with imines have been developed. The reactions proceed under mild conditions and provide the corresponding products with high enantiomeric excess. [ABSTRACT FROM AUTHOR]

The catalytic enantioselective Mannich reaction promoted by chiral bifunctional organocatalysts is described. The treatment of α-fluoro-β-keto esterswith N-Boc aldimines under mild reaction conditions afforded the corresponding β-aminated α-fluoro-β-keto esters with excellent enantioselectivities (up to 98% ee). [ABSTRACT FROM AUTHOR]

The catalytic enantioselective Mannich reaction promoted by chiral bifunctional organocatalysts is described. The treatment of α-fluoro-b-keto esters with N-Boc aldimines under mild reaction conditions afforded the corresponding β-aminated α-fluoro- β-keto esters with excellent enantioselectivities (up to 98% ee). [ABSTRACT FROM AUTHOR]

Copper-catalyzed Mannich reactions of terminal alkynes and secondary amines with aqueous formaldehyde can be accelerated by the use of a catalytic amount of an imidazole ligand carrying a long alkyl chain. The alkyl chain shows an efficient steric effect and helps the reaction. This imidazole ligand is efficient for various substrates, including even bulky alkynes. [ABSTRACT FROM AUTHOR]