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The magnesium-mediated addition of bromoform to conjugated electron-deficient alkenes and imines, such as para -quinone methides (p -QMs) and aurone-derived azadienes, respectively, is reported here for the first time. While p -QMs undergo exclusive and hitherto unreported 1,6-addition of bromoform to afford benzylic tribromomethylated diarylmethanes, aurone-derived azadienes undergo both 1,2- and 1,4-additions to furnish α- and γ-tribromomethylamines. A mechanism involving the intermediacy of the tribromomethyl radical has been proposed based on control experiments and EPR studies. Representative synthetic transformations have also been carried out. [ABSTRACT FROM AUTHOR]

A dearomatization-guided and (3+2) cycloaddition-triggered annulation reaction of in situ formed isoquinolinium ylides with sulfamate-derived cyclic imines is reported, offering a cogent synthesis of tetracyclic 1,3-benzoxazepine frameworks in high yields. The protocol features successive ring-forming and ring-breaking events in a cascade fashion and is also scalable. [ABSTRACT FROM AUTHOR]

The development of new catalytic systems that enable regio- and chemoselective construction of diversely functionalized oxazocines is an important topic in organic synthesis and pharmacochemistry. Herein, a novel Pd/Mengphos complex was designed and applied in a palladium-catalyzed high-order [4+4] cycloaddition of 2-substituted allylic carbonates to α,β-unsaturated imines, allowing facile access to versatile oxazocines in good yields with excellent b / l and Z / E selectivities (up to 92% yield and complete b / l and Z / E selectivities). The reaction exhibited a broad substrate scope, mild reaction conditions, and good functional group compatibility. In addition, an asymmetric version has also been tested, affording the desired oxazocines in moderate to good enantioselectivity. [ABSTRACT FROM AUTHOR]

α-Functionalisation of cyclic imines is explored. The cyclic imine substrates are synthesised from their respective halonitrile precursors using a nucleophilic addition/cyclisation sequence. Selective monohalogenation of the cyclic imines yields α-haloimines, which serve as a platform to obtain various α-hydroxyimine derivatives. In addition, an unusual tautomerisation and oxidation sequence is observed in the attempted preparation of α-hydroxyimines. [ABSTRACT FROM AUTHOR]

We have revisited the imine-anion-mediated Smiles rearrangement for the synthesis of ortho -hydroxyphenyl arylketimines. Detailed examinations revealed that migration of various aromatic groups, previously considered to be unsuited to SN Ar-type reactions, such as electron-rich or sterically hindered aromatic groups, can be accomplished by introducing bulky 9-anthryllithium as a nucleophile. Among the aromatic groups examined, naphthyl groups (1- and 2-naphthyl groups) exhibited an excellent performance, and their migration ability was well illustrated by the reaction with less bulky nucleophiles. [ABSTRACT FROM AUTHOR]

A new and efficient strategy for the stereoselective synthesis of tetrahydropyridino- and deazepanopyrrolo[1,2- c ]imidazolidines has been developed. Annulation of acylethynylpyrroles with six- and seven-membered cyclic imines (MeCN/THF, 20–25 °C, 24–72 h) leads to tetrahydropyrrolo[1′,2′:3,4]imidazo[1,2- a ]pyridines and hexahydropyrrolo[1′,2′:3,4]imidazo[1,2- a ]azepines with (E)-acylethenyl moiety in 28–96% yields. [ABSTRACT FROM AUTHOR]

This article discusses the development of new methods for synthesizing N-unsubstituted ketimines, which are valuable compounds used in the production of nitrogen-containing compounds. The researchers focused on using ketones as starting materials and scandium triflate as a catalyst. They optimized the reaction conditions and explored the effects of solvents and Lewis acid catalysts. The research provides more moderate and environmentally friendly methods for synthesizing N-unsubstituted ketimines, and also explores their application in one-pot reactions. The article also discusses the proposed reaction mechanism and hopes to inspire further development in related processes. [Extracted from the article]

However, for this endeavor we would directly use aniline B 22 b [21] to conclude our MCR procedure, because necessity required it; condensation of aniline B 22 b with either propionaldehyde or isobutyraldehyde had failed to afford a sufficiently pure imine to proceed. Keywords: ortho -quinone methides; marilines; imines; dihydrooxazoles; anilines; isoindolin-1-ones; phthalimidines; salicylaldehydes EN ortho -quinone methides marilines imines dihydrooxazoles anilines isoindolin-1-ones phthalimidines salicylaldehydes 3297 3302 6 09/29/23 20231018 NES 231018 Graph Numerous phthalimidines found in nature display a wide range of biological activities. The solution was quenched with saturated NaHCO SB 3 sb solution (3 mL) and extracted with Et SB 2 sb O (3 × 3 mL). Specifically, we have shown that various I o i -QM intermediates can be engaged by anilines, dihydrooxazoles, and imines to arrive at N-arylated, N-hydroxy ethylated, and free-N amines, respectively. [Extracted from the article]

[40] Recently, pyrazolone-based MBH carbonates have emerged as versatile precursors to access spiropyrazolone scaffolds. Keywords: annulation; spiropyrazolones; diastereoselectivity; Morita-Baylis-Hillman carbonates; spirooxindoles EN annulation spiropyrazolones diastereoselectivity Morita-Baylis-Hillman carbonates spirooxindoles 1732 1738 7 08/18/23 20230901 NES 230901 Graph The construction of spiro carbocyclic/heterocyclic structures has received enormous attention from synthetic and medicinal-chemistry researchers in recent decades. Under the optimized reaction conditions, the pyrazolone MBH carbonates B 1a b - B c b reacted efficiently with the 3-methyleneoxindoles B 2a b - B v b to afford the corresponding spiropyrazolone oxindole derivatives B 3a b - B x b in good to excellent yields (up to 98%) and with very high diastereoselectivities (dr 99:1) (Scheme 1). [36] Despite these recent advances in synthesizing spiropyrazolone-fused oxindole derivatives, few methods have been described for the synthesis of a spirocyclic molecule bearing three different scaffolds, such as pyrazolone, oxindole, and cyclopentene, in a diastereoselective manner. [Extracted from the article]

[21][24] We wish to report herein our synthetic approach toward -hydroxyamino ketones, which involves the radical acylation of nitrone with 2-acylbenzothiazolene under organophotoredox catalysis (route C). Metal- and Additive-Free Synthesis of -Hydroxyamino Ketones Enabled by Organophotocatalyst Hydroxyamino ketone, hydroxylamine, nitrone, benzothiazoline, metal-free, organophotocatalyst Keywords: hydroxyamino ketone; hydroxylamine; nitrone; benzothiazoline; organophotocatalyst; metal-free EN hydroxyamino ketone hydroxylamine nitrone benzothiazoline organophotocatalyst metal-free 1391 1394 4 07/11/23 20230725 NES 230725 Graph Nitrogen-containing compounds are prevalent in organic compounds, and a range of novel catalytic approaches have been extensively explored. [Extracted from the article]

Keywords: chiral phosphoric acid; organocatalysis; cycloaddition; alkenes; alkynes EN chiral phosphoric acid organocatalysis cycloaddition alkenes alkynes 1200 1214 15 06/19/23 20230704 NES 230704 1 Introduction Asymmetric cycloaddition reaction is the most powerful strategy for the construction of various enantioenriched carbocycles and heterocycles, [1] because it provides an efficient and completely atom-economical route from simple precursors. In order to achieve this goal, we needed to overcome the following issues: (1) realization of efficient cycloaddition of alkynes with appropriate partners; (2) the installation of suitable groups onto alkynes to avoid free rotation around the potential C-C axes; (3) the choice of a competent chiral catalyst to promote the designed cycloaddition reactions and to control the stereoselectivity. 3 CPA-Catalyzed Cycloaddition of Alkynes Although the CPA-catalyzed cycloaddition of alkenes have been well documented, the CPA-catalyzed asymmetric cycloaddition reaction of alkynes is still lacking. On the other hand, the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [4+2] cycloaddition, an alkyne-type Povarov cycloaddition, and an auto-oxidation reaction. [Extracted from the article]

A direct approach toward the construction of furoxan-sydnone imine double NO-donors involving the NOBF4-mediated nitrosation–cyclization sequence of α-amino nitriles as a key synthetic step was developed. The described protocol excludes the isolation of carcinogenic N -nitrosamines, operates broad substrate scope, and enables the preparation of fully substituted sydnone imines linked to the furoxan ring via different linkers or directly through C–C bond. Synthesized library of furoxan-sydnone imine hybrids demonstrated a promising ability to release NO in a wide range of concentrations which is useful for various biomedical insights. [ABSTRACT FROM AUTHOR]

A mild and efficient organocatalyzed [3+2] cycloaddition of isatin-derived ketimines and 2-ylideneindane-1,3-diones has been realized. The resulting spiro[oxindole-3,2′-pyrrolidine]s bearing both a spiro indane-1,3-dione motif and a trifluoromethyl group were obtained in high yields with good diastereo- and enantioselectivities. [ABSTRACT FROM AUTHOR]

1-Aminophosphonates are valuable compounds with wide range of applications in biological and industry. Various reaction conditions and catalysts have been reported for the synthesis of 1-aminophosphonates via three-component (dialkyl phosphite + aldehyde + amine) or two-component reaction (dialkyl phosphite + imine). Here a solvent-free synthesis of 1-aminophosphonates under very mild reaction conditions is reported. The three-component condensation reactions of dialkyl phosphite, carbonyl compound, and an amine gave 1-aminophosphonates in good to excellent yields under solvent- and catalyst-free conditions at ambient temperature. Hydrophosphorylation of imines in the presence of dialkyl phosphite under the same conditions gave also 1-aminophosphonates in good to excellent yields. These results showed that the reaction needs no catalyst or solvent for activation. It seems a tautomeric form of dialkyl phosphite (as one of the components) catalyzed the reaction. The reaction yield decreased using any solvent. In addition, a novel method is reported for the synthesis of N -deprotected 1-aminophosphonates (analogues of 1-amino acids) from N -PMP 1-aminophosphonate in the presence of TCCA. To understand the activity of the dialkyl phosphite under solvent-free conditions, the DFT calculations have provided insight into the basis of this activity. [ABSTRACT FROM AUTHOR]

An enantioselective intramolecular heterocyclization with in situ generated 3-hydroxyisoindolinone-derived N -acyliminium ions has been successfully accomplished. In the presence of a catalytic amount of a chiral phosphoric acid, functionalized 3,3-disubstituted isoindolinones bearing N -acyl- N , O -acetal moieties were obtained with good yields and a high level of stereocontrol (up to 98:2 er). This efficient method proceeds under mild conditions and exhibits broad scope with respect to both 3-hydroxyisoindolinones and hydroxyl partners. [ABSTRACT FROM AUTHOR]

Catalytic asymmetric 1,3-dipolar cycloaddition reactions of activated isocyanides with various 2π dipolarophiles have been intensively studied, affording a wide range of enantioenriched five-membered N-heterocycles. In sharp contrast, the catalytic enantioselective higher-order cycloaddition of activated isocyanides has not been achieved yet. We present here our recent work on the development of an unprecedented silver-catalyzed highly diastereo- and enantioselective [3+3] cycloaddition of activated isocyanides with azomethine imines. This method features high efficiency, good to excellent stereocontrol, wide substrate scope, as well as operational simplicity. It is also noteworthy that the same catalytic system was proved to be suitable for not only the late-stage functionalization of complex bioactive molecules but also the kinetic resolution of racemic azomethine imines. 1 Introduction 2 Results and Discussion 3 Summary and Outlook [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]

N -Sulfinyl metalloenamines, generated by deprotonating α-linear N - tert -butanesulfinyl ketimines, reacted with nitroalkenes via stereoselective conjugate addition to give Michael adducts with opposite stereochemistry to that obtained using α-branched sulfinylketimines. In the presence of excess base (2.5 equiv t -BuOK), the adducts derived from α-linear ketimines were further stereoselectively deprotonated to afford the corresponding kinetically favorable N -sulfinyl (Z)-enamine derivatives in good yields with good stereoselectivities. A reaction model was proposed to rationalize the observed stereochemistry. [ABSTRACT FROM AUTHOR]

Herein, we describe the synthesis of a wide variety of imines through oxidative coupling of alcohols and aromatic amines catalyzed by Mn complexes bearing N^N triazole ligands. A wide variety of imines in excellent yields (up to 99%) have been prepared. Mn-based catalysts proved to be highly efficient and versatile, allowing for the first time the preparation of several imines containing N-based heterocycles. [ABSTRACT FROM AUTHOR]

This review summarizes recent developments in the area of Brønsted acid catalyzed, enantioselective cycloadditions of ortho -quinone methides, ortho -quinone methide imines as well as heterocyclic indole- and pyrrole-based methides. In a straightforward and single-step transformation complex polycyclic N- and O-heterocyclic scaffolds are accessible, with typically good yields and excellent stereocontrol, from simple benzyl and heterobenzyl alcohols upon acid-catalyzed dehydration. The transient precursors are hydrogen-bonded to a chiral Brønsted acid which controls the enantioselectivity of the process. 1 Introduction 2 Cycloadditions of ortho -Quinone Methides 2.1 Brønsted Acid Catalyzed Processes 2.2 Cooperative Brønsted Acid/Transition-Metal-Catalyzed Processes 3 Cycloadditions of ortho -Quinone Methide Imines 4 Cycloadditions of Indolyl-3-methides 5 Cycloadditions of Indolyl-2-methides 5.1 Brønsted Acid Catalyzed Processes 5.2 Cooperative Brønsted Acid/Transition-Metal-Catalyzed Processes 6 Cycloadditions of Pyrrolyl-2-methides 7 Cycloadditions of Pyrrolyl-3-methides 8 Conclusions [ABSTRACT FROM AUTHOR]

Chiral α-tertiary amines, a motif present in α,α-disubstituted α-amino acids, in a wide range of natural products, and many drugs and drug candidates, are important targets in organic chemistry. Among the possible strategies, 1,2-addition to chiral N -sulfinyl-ketimines is one of the best routes to form chiral α-tertiary amines with a high level of stereoselectivity. In this review, we focus first on the addition of organometallic reagents or other nucleophiles as enols or ylides to chiral N -sulfinylketimines. Then secondly we cover a selection of applications of these additions in the synthesis of valuable biologically active compounds. 1 Introduction 2 1,2-Addition Reaction Methodologies 2.1 Organolithium Reagent Additions 2.2 Grignard Additions 2.3 Organozinc Reagent Additions 2.4 Organoindium Reagent Additions 2.5 Organoboron Reagent Additions 2.6 Strecker Reactions 2.7 Palladium-Catalyzed Reactions 2.8 Enols, Enolates, and Other Deprotonated Reagent Additions 2.9 Ylide Additions 2.10 Heteroatom Nucleophiles 2.11 Miscellaneous Reactions 3 Applications to the Synthesis of Biologically Active Molecules 4 Conclusions [ABSTRACT FROM AUTHOR]

A new synthetic route to indazolo[2,3- a ]quinoxaline derivatives is described. The strategy is based on the 1,3-dipolar cycloaddition of arynes to quinoxaline–sydnone derivatives as a key step. The polyaromatic sydnones were prepared through a copper-promoted intramolecular cyclization of the C-4 position of sydnones on imines. [ABSTRACT FROM AUTHOR]

Dimethylalkynylaluminum reagents derived from terminal alkynes and trimethylaluminum underwent addition to various N -activated α-amido sulfones to produce the corresponding alkynylamines in moderate to excellent yields. The optimized protocol avoids the preparation and isolation of relatively unstable N -activated imines that are generated in situ from their corresponding, stable, N -activated α-amido sulfones. This methodology provides access to a wide range of alkynylamines containing N -carbamoyl, -acyl, and -sulfonyl moieties. [ABSTRACT FROM AUTHOR]

A tandem approach was developed for the efficient synthesis of substituted chromeno[4,3- b ]quinolines from arylamines and O -cinnamyl salicylaldehydes under metal-catalyst- and photosensitizer-free reaction conditions. Our protocol is based on an inexpensive I2 /DMSO system in which molecular iodine first acts as a Lewis acid to promote the formation of the corresponding imine bearing the alkene moiety; then, this species fulfills a second role by catalyzing an intramolecular aza-Diels–Alder cycloaddition to generate the respective tetrahydrochromenoquinoline as an intermediate. Finally, the dual behavior of DMSO as an oxidant and as a solvent proved crucial at this stage, allowing the regeneration of I2 and promoting the aromatization of the tetrahydrochromenoquinoline intermediates to yield the desired 7-aryl-6 H -chromeno[4,3- b ]quinolines. This protocol is mild and easy to perform, features high step-economy (tandem process) and provides a new access to biologically important nitrogen- and oxygen-containing heterocyclic molecules. [ABSTRACT FROM AUTHOR]

Aza-Diels–Alder reactions are straightforward processes for the construction of N -heterocycles, featuring inherent atom-economy and stereospecificity. Intramolecular strategies allow the formation of bicyclic core structures with up to three stereocenters within a single step. Herein, this concept is combined with the chemistry of chiral Brønsted acid bound ortho -quinone methide imines to generate a range of interesting fused tetrahydroquinolines in a diastereo- and enantioselective- manner. [ABSTRACT FROM AUTHOR]

The base-induced formal [4+3] cycloaddition reaction of C,N-cyclic azomethine imines with aza- ortho -quinone methides, generated in situ, is reported. This protocol provided an efficient method for the synthesis of biologically important 1,2,4-triazepine derivatives, with a wide substrate scope and excellent functional-group tolerance, and it gives moderate to excellent yields under mild conditions. Several of the derivatives exhibited in vitro antitumor activities against the A2780 cell line in a screening of the cancer cell lines HCT-116, H2228, and A2780 by an MTT assay. [ABSTRACT FROM AUTHOR]

An aza-Peterson olefination methodology to access 1,3-dienes and stilbene derivatives from the corresponding allyl- or benzyltrimethylsilane is described. Silanes can be deprotonated using Schlosser's base and added to N -phenyl imines or ketones to directly give the desired products in high yields. [ABSTRACT FROM AUTHOR]

Aromatic C–H allylation of N -sulfonyl ketimines with allyl alcohol or allyl phenyl ether as an allyl source is catalyzed by a cationic iridium complex. The presence of a catalytic amount of a pyridine derivative was found to be essential for the reaction. In contrast, direct C–H allylation of ketimines derived from benzophenone derivatives and p -methoxyaniline with allyl phenyl ether proceeded in the absence of pyridine derivatives. [ABSTRACT FROM AUTHOR]

The synthesis of a series of fused diaziridines, which are difficult to access by existing methods, was achieved by the reaction of cyclic secondary amines with p -toluenesulfonamide in the presence of N -bromosuccinimide (NBS) and a suitable base. This oxidation system enables the efficient in situ formation of the key intermediates, which are N -bromoamines (a precursor of cyclic imines) and N -bromosulfonamides. In addition, an alternative method using N -bromo- N -sodio- p -toluenesulfonamide (bromamine-T) in the presence of a catalytic amount of CF3 CO2 H for the synthesis of fused diaziridines is also reported. [ABSTRACT FROM AUTHOR]

Transition-metal-catalyzed nucleophilic C–H addition of hydrocarbons to polar unsaturated bonds could intrinsically avoid prefunctionalization of substrates and formation of waste byproducts, thus featuring high step- and atom-economy. As the third most abundant transition metal, manganese-catalyzed C–H addition to polar unsaturated bonds remains challenging, partially due to the difficulty in building a closed catalytic cycle of manganese. In the past few years, we have developed manganese catalysis to enable the sp2-hydrid C–H addition to polar unsaturated bonds (e.g., imines, aldehydes, nitriles), which will be discussed in this personal account. 1 Introduction 2 Mn-Catalyzed N-Directed C(sp2)–H Addition to Polar Unsaturated Bonds 3 Mn-Catalyzed O-Directed C(sp2)–H Addition to Polar Unsaturated Bonds 4 Conclusion [ABSTRACT FROM AUTHOR]

The stereoselective synthesis of substituted morpholine derivatives has been achieved through a two-step process involving diastereoselective addition of a Grignard reagent to a sulfinyl imine, followed by cyclization. [ABSTRACT FROM AUTHOR]

Under the catalysis of PhCO2 H, the 1,3-dipolar [3+2] cyclo-addition between pyrazolone-based olefins and N , N ′-cyclic azomethine imines proceeded readily, thus delivering structurally novel spiropyrazolones with up to 98% yield and >20:1 dr. The relative stereochemical configuration of the obtained spiropyrazolones was unambiguously -assigned by X-ray single-crystal structure analysis. The diastereoselective formation of the title spiropyrazolones was interpreted by the hypothesized reaction mechanism. [ABSTRACT FROM AUTHOR]

1,3-Bifunctional nucleophilic allylation reagents play an important role in organic synthesis. In this short review, we summarize the methods for the preparation of 1,3-bifunctional reagents and their reactions with various electrophiles. Synthetic applications of these reagents in the context of complex molecule synthesis are also discussed. 1 Introduction 2 Reagent Synthesis 2.1 Symmetrical Reagents 2.2 Unsymmetrical Reagents 2.2.1 Bis-silane and Silyl-stannane Reagents 2.2.2 Bis-boron and Silyl-boron Reagents 3 Synthetic Applications 3.1 Allylation of Aldehydes 3.2 Allylation of Ketones 3.3 Allylation of Imines 3.4 Allylation of Other Electrophiles with 1,3-Bifunctional Allylation Reagents 4 Summary [ABSTRACT FROM AUTHOR]

An efficient stereocontrolled preparation of 2-substituted pyrrolidines and 5-substituted indolizidin-7-ones, by using chiral N - tert -butanesulfinyl imines derived from 4-halobutanal as starting materials, is detailed. Addition of Grignard reagents and a decarboxylative Mannich- reaction with β-keto acids involving these chiral imines proceeded with high diastereoselectivity. The synthesis of the pyrrolidinic alkaloids (–)-bgugaine, (+)-villatamine B, (–)-norhygrine, trans -dendrochrysanine, and (–)-ruspolinone demonstrated the utility of this methodology. [ABSTRACT FROM AUTHOR]

Visible-light photoredox catalysis has recently emerged as a powerful tool for the development of new and valuable chemical transformations under mild conditions. Visible-light promoted enantioselective radical transformations of imines and iminium intermediates provide new opportunities for the asymmetric synthesis of amines and the asymmetric β-functionalization of unsaturated carbonyl compounds. In this review, recent advances on the catalytic asymmetric radical functionalization of imines and iminium intermediates are summarized. 1 Introduction 2 Enantioselective Radical Functionalization of Imines 2.1 Asymmetric Reduction 2.2 Asymmetric Cyclization 2.3 Asymmetric Addition 2.4 Asymmetric Radical–Radical Coupling 3 Enantioselective Radical Functionalization of Iminium Ions 3.1 Asymmetric Radical Alkylation 3.2 Asymmetric Radical Acylation 4 Conclusion [ABSTRACT FROM AUTHOR]

Because molecular iodine and hydrosilanes are stable to both air and moisture, reactions using these reagents are easy to operate and require mild reaction conditions. Molecular iodine and a hydrosilane were used to reduce N -sulfonyl aldimines to the corresponding N -alkylsulfonamides. This transformation is a practical method for the synthesis of N -alkylsulfonamides. [ABSTRACT FROM AUTHOR]

In the presence of Pd2 (dba)3 ·CHCl3 (2.5 mol%), PPh3 (10 mol%), and 60% NaH (1.5 equiv), the formal [5+3] cycloaddition between isatin-based α-(trifluoromethyl)imines and vinyloxiranes proceeded readily in 1,2-DCE at 40 ℃ and afforded cis -configured medium-heterocycle-fused spirooxindoles in the reasonable chemical yields with >20:1 dr. The relative stereochemical configuration of the title products was identified by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Tetrahydroisoquinoline (THIQ) scaffolds are important structural units that widely exist in a variety of natural alkaloids and synthetic analogues. Asymmetric synthesis of C1-chiral THIQ is of particular importance due to its significant pharmaceutical, agrochemical, and other biological activities, and the usually distinct bioactivities exhibited by the two enantiomers. In this review, we highlight the significant advances achieved in this field, present recent asymmetric synthesis with imines in isoquinoline rings ordered according to the sequence of various substrate types. New strategies could be inspired and more types of substrates need further development. 1 Introduction 2 Catalytic Asymmetric Reaction of Dihydroisoquinolines 2.1 Asymmetric Reactions of 3,4-Dihydroisoquinolines 2.2 Asymmetric Reactions of Dihydroisoquinolinium Salts 2.3 Asymmetric Reactions of C , N -Cyclic N ′-Acyl Azomethine Imines 2.3.1 NED [3+2] Cycloaddition of C , N -Cyclic N ′-Acyl Azomethine Imines 2.3.2 IED [3+2] Cycloaddition of C , N -Cyclic N ′-Acyl Azomethine Imines 2.3.3 [3+3] Cycloaddition of C , N -Cyclic N ′-Acyl Azomethine Imines 2.3.4 [4+3] Cycloaddition of C , N -Cyclic N ′-Acyl Azomethine Imines 2.3.5 Asymmetric Addition Reactions to C , N -Cyclic N ′-Acyl Azomethine Imines 2.4 Asymmetric Reactions of C , N -Cyclic Nitrones 3 Catalytic Asymmetric Mannich Reactions of Isoquinolines 4 Conclusions and Perspectives [ABSTRACT FROM AUTHOR]

An efficient method for the stereoselective synthesis of α-methylene-γ-lactams via quaternary 3-aminooxindoles with very high selectivity (up to 98% ee) is described. The methodology leads to the construction of sterically congested chiral quaternary 3-aminooxindole adducts in good yield and with moderate to excellent diastereoselectivity (dr up to 95:5). The relative stereochemistry of the chiral quaternary 3-aminooxindoles adduct and the spiro-α-methylene-γ-lactam was confirmed to be syn by single-crystal X-ray structure analysis. Furthermore, the α-methylene-γ-lactam was successfully transformed into a range of chiral synthons. [ABSTRACT FROM AUTHOR]

This work details the synthesis of 22 new chiral VANOL ligands that differ by the nature of the substituent in the 3- and 3′-positions of the ligand. These ligands were incorporated into boroxinate catalysts that were used to screen the catalytic asymmetric aziridination of benzhydryl imines with ethyl diazoacetate. Each catalyst was screened in the reaction of imines generated from benzaldehyde and cyclohexanecarboxaldehyde and some with 4-nitro- and 4-methoxybenzaldehyde. In addition, the first report of the effect of the ester substituent of the diazoacetate ester on the asymmetric induction in these aziridination reactions is presented. The first X-ray structure of a boroxinate catalyst generated from a VANOL-derived ligand is also reported. [ABSTRACT FROM AUTHOR]

Simple ketone starting materials with a halide leaving group and an alkene were prepared in one step and heated with glycine or glycine esters to promote a tandem imine formation, cyclization, and dipolar cycloaddition cascade. The chemistry was also feasible with acetylhydrazide. In each case a single stereoisomer of the tricyclic amine or pyrazolidine product was formed and the stereochemistry was verified by single crystal X-ray diffraction. When the reaction with glycine, which occurs with loss of CO2 , was unsuccessful, the cascade process could be promoted by cross metathesis to give the vinyl sulfone starting material that provides a more reactive dipolarophile. Reductive cleavage of the pyrazolidine gave a spirocyclic diamine product. [ABSTRACT FROM AUTHOR]

Umpolung strategies are of considerable interest to organic chemists because they provide alternative synthetic routes to those imposed by the natural polarity of classical synthons. Reverse-polarity reactions of aldehydes, α,β-unsaturated carbonyl compounds, and imines are deeply embedded in the methodology of organic synthesis. In recent years, umpolung of enols and enamines has received much attention as a novel strategy to access α-substituted ketones. Here, state-of-the-art approaches to umpolung of enamine reactivity are discussed, with a particular focus on recent developments in this field from the author's research group. 1 Introduction 2 Approaches toward Umpolung of Enamines 3 Umpolung of Enamines through Single-Electron Oxidation 4 Azadienes as Synthetic Equivalents of Enamine Umpolung Synthons 5 Enamines Possessing a Leaving Group at the Nitrogen Atom 6 Enamines Possessing a Directing Group at the Nitrogen Atom 7 Summary and Outlook [ABSTRACT FROM AUTHOR]

Vinylogous aza-Morita–Baylis–Hillman (aza-MBH) reactions of a vinylcyclopentenone with N -Boc imines provide the corresponding γ-adducts in high regioselectivity (10 examples). While the corresponding reactions with N -Ts imines give the α-adducts and γ-adducts depending on the catalyst, those with N -Boc imines proceed in a γ-selective manner, irrespective of the promoter. The nature of the protecting groups on the nitrogen of the aldimines is found to play a key role in the regiochemical course of vinylogous aza-MBH reactions. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of perfluoroalkylated derivatives of γ-carboline and pyrrolopyrazine was elaborated. Pictet–Spengler reaction of isotryptamine and 2-(pyrrol-1-yl)ethanamine with trifluoromethylated carbonyls and 2-perfluoroalkyl-substituted five-, six-, and seven-membered cyclic imines was studied. It was found that this approach opens efficient access to a family of alkaloid-like compounds bearing a CF3 or C2 F5 group in the structure. In the case of the iso-Pictet–Spengler reaction with 2-perfluoroalkyl-substituted cyclic imines, a series of γ-carbolines bearing an aminoalkyl group were prepared. [ABSTRACT FROM AUTHOR]

Tricyclic imines inheriting a 2-azabicyclo[2.2.2]octane (isoquinuclidine) scaffold were provided with high regioselectivity in moderate to very good yields by a smooth, broadly applicable intramolecular hetero-Diels–Alder reaction of various 4-ω-alkenyl-substituted 1,4-dihydropyridines (DHPs) under trifluoroacetic acid catalysis. The required- 4,4-disubstituted 1,4-DHPs were obtained by introduction of ω-alkenyl moieties of varying chain length via diorganomagnesium reagents into the 4-position of diversely 4-substituted pyridines after prior N-activation with triisopropylsilyltriflate. [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]

The development of new strategies for the preparation of chiral amines is an important objective in organic synthesis. In this Synpacts , we summarize our approach for catalytically accessing nucleophilic aminoalkyl metal species from 2-azadienes, and its application in generating a number of important but elusive chiral amine scaffolds. Reductive couplings with ketones and imines afford 1,2-amino tertiary alcohols and 1,2-diamines, respectively, whereas fluoroarylations of gem -difluoro-2-azadienes deliver α-trifluoromethylated benzylic amines. 1 Introduction 2 Background: Umpolung Strategies for Preparing Chiral Amines 3 Background: 2-Azadienes 4 Reductive Couplings of 2-Azadienes 5 Fluoroarylations of gem -Difluoro-2-azadienes 6 Summary and Outlook [ABSTRACT FROM AUTHOR]

Under bifunctional squaramide and thiourea organocatalysis, a series of vicinally bis(trifluoromethyl)-substituted 3,3′-pyrrolidinyl spirooxindoles were successfully synthesized via 1,3-dipolar cycloaddition reactions of 3-(trifluoroethylidene)oxindoles with diethyl 2-((2,2,2-trifluoroethyl)imino)malonate and N -(2,2,2-trifluoroethyl)isatin ketimines. The highlight of this protocol is the efficient construction of the vicinally bis(trifluoromethyl)-substituted pyrrolidine unit of spirooxindoles, including multiple contiguous stereogenic centres, in excellent yields and stereoselectivities. [ABSTRACT FROM AUTHOR]