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Enamines are versatile building blocks for the synthesis of biologically active compounds. Nevertheless, only a limited number of strategies have been reported for preparing trisubstituted enamines in a regio‐ and stereoselective manner. Herein, we report a regiocontrolled 6‐endo and 5‐exo tethered carboamination of propargylic alcohols for the synthesis of trisubstituted enamines. High regioselectivity was achieved through fine‐tuning of the amine protecting group during the Pd‐catalyzed carboamination. The introduced trifluoromethylated tether enables further stereoselective functionalizations, such as hydrogenation and fluorination. [ABSTRACT FROM AUTHOR]

The low‐electron count, air‐stable, platinum complexes [Pt(ItBu')(ItBu)][BArF] (C1) (ItBu=1,3‐di‐tert‐butylimidazol‐2‐ylidene), [Pt(SiPh)3(ItBuiPr)2][BArF] (C2) (ItBuiPr=1‐tert‐butyl‐3‐iso‐propylimidazol‐2‐ylidene), [Pt(SiPh)3(ItBuMe)2][BArF] (C3), [Pt(GePh3)(ItBuiPr)2][BArF] (C4), [Pt(GePh)3(ItBuMe)2][BArF] (C5) and [Pt(GeEt)3(ItBuMe)2][BArF] (C6) (ItBuMe=1‐tert‐butyl‐3‐methylimidazol‐2‐ylidene) are efficient catalysts (particularly the germyl derivatives) in both the silylative dehydrocoupling and hydrosilylation of electron rich alkenes derived from enamines. The steric hindrance exerted by the NHC ligand plays an important role in the selectivity of the reaction. Thus, bulky ligands are selective towards the silylative dehydrocoupling process whereas less sterically hindered promote the selective hydrosilylation reaction. The latter is, in addition, regioselective towards the β‐carbon atom of both internal and terminal enamines, leading to β‐aminosilanes. Moreover, the syn stereochemistry of the amino and silyl groups implies an anti Si−H bond addition across the double bond. All these facts point to a mechanistic picture that, according to experimental and computational studies, involves a non‐classical hydrosilylation process through an outer‐sphere mechanism in which a formal nucleophilic addition of the enamine to the silicon atom of a platinum σ‐SiH complex is the key step. This is in sharp contrast with the classical Chalk–Harrod mechanism prevalent in platinum chemistry. [ABSTRACT FROM AUTHOR]

Aminocatalysis is a well‐established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored. Herein, we present the successful merger of electrochemistry and aminocatalysis to perform SOMO‐type transformations, expanding the toolkit for asymmetric electrochemical synthesis. The methodology harnesses electricity to drive the oxidation of catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading to α‐alkylated aldehydes. Crucially, mechanistic studies highlight how this electrochemical strategy is enabled by the use of a redox shuttle, 4,4′‐dimethoxybiphenyl, to prevent catalyst degradation and furnishing the coveted compounds in good yield and high enantioselectivity. [ABSTRACT FROM AUTHOR]

β‐Keto‐enamine‐linked 2D covalent organic frameworks (COFs) have emerged as highly robust materials, showing significant potential for practical applications. However, the exclusive reliance on 1,3,5‐triformylphloroglucinol (Tp aldehyde) in the design of such COFs often results in the production of non‐porous amorphous polymers when combined with certain amine building blocks. Attempts to adjust the crystallinity and porosity by a modulator approach are inefficient because Tp aldehyde readily forms stable β‐keto‐enamine‐linked monomers/oligomers with various aromatic amines through an irreversible keto‐enol tautomerization process. Our research employed a unique protection‐deprotection strategy to enhance the crystallinity and porosity of β‐keto‐enamine‐linked squaramide‐based 2D COFs. Advanced solid‐state NMR studies, including 1D 13C CPMAS, 1H fast MAS, 15N CPMAS, 2D 13C−1H correlation, 1H−1H DQ‐SQ, and 14N−1H HMQC NMR were used to establish the atomic‐level connectivity within the resultant COFs. The TpOMe‐Sqm COFs synthesized utilizing this strategy have a surface area of 487 m2 g−1, significantly higher than similar COFs synthesized using Tp aldehyde. Furthermore, detailed time‐dependent PXRD, solid‐state 13C CPMAS NMR, and theoretical DFT studies shed more light on the crystallization and linkage conversion processes in these 2D COFs. Ultimately, we applied this protection‐deprotection method to construct novel keto‐enamine‐linked highly porous organic polymers with a surface area of 1018 m2 g−1. [ABSTRACT FROM AUTHOR]

Enamides, functional derivatives of enamines, play a significant role as synthetic targets. However, the stereoselective synthesis of these molecules has posed a longstanding challenge in organic chemistry, particularly for acyclic enamides that are less thermodynamically stable. In this study, we present a general strategy for constructing β‐borylenamides by C−H borylation, which provides a versatile platform for generating the stereodefined enamides. Our approach involves the utilization of metalloid borenium cation, generated through the reaction of BBr3 and enamides in the presence of two different additives, avoiding any exogenous catalyst. Importantly, the stereoconvergent nature of this methodology allows for the use of starting materials with mixed E/Z configurations, thus highlighting the unique advantage of this chemistry. Mechanistic investigations have shed light on the pivotal roles played by the two additives, the reactive boron species, and the phenomenon of stereoconvergence. [ABSTRACT FROM AUTHOR]

The borylation of Csp3−H bonds is a challenging transformation that is typically restricted to transition metal catalysis. Herein, we report the site‐selective metal‐free Csp3−H borylation of saturated cyclic amines. It is possible to selectively borylate piperidine derivatives at the α or β positions according to the reaction conditions. The mechanism was supported by NMR spectroscopy, calorimetry experiments and density functional theory (DFT) computations. It suggests that the piperidine is dehydrogenated by complexation with BBr3 to produce an enamine intermediate, which is in turn borylated at either the α or β position according to the reaction conditions. [ABSTRACT FROM AUTHOR]

Alkyne hydroamination is an effective approach for the production of enamines and enamine‐containing N‐heterocycles. However, stereoselectivity control is a considerable challenge in this reaction because of the electronic repulsion between an incoming nitrogen lone pair and the alkyne π‐system. Herein, we propose a methodology involving β‐regio‐ and Z‐selective alkyne hydroamination by using tetrafluoro‐λ6‐sulfanyl (SF4) alkynes under superbasic, naked anion conditions. The reaction is compatible with a wide variety of N‐heterocycles, including indoles, carbazoles, pyrazoles, and imidazoles, and selectively furnishes SF4‐linked Z‐vinyl enamines with β‐regioselectively. Moreover, the method can be extended to the β‐ and Z‐controlled, base‐mediated alkyne hydrophenoxylation with phenols to provide SF4‐linked Z‐vinyl ethers in high yields. As the SF4 unit has attracted attention as a bioisostere for alkynes, p‐benzenes, bicyclo[1.1.1]pentyl (BCP) groups, and cubanes in medicinal chemistry, this chemistry represents an effective approach to creating novel drug candidates incorporating SF4‐containing molecules. [ABSTRACT FROM AUTHOR]

A new 15‐membered‐macrocyclic molecular entity, oxa‐TriQuinoline (o‐TQ), was designed and synthesized. In o‐TQ, three oxygen atoms were joined onto three quinoline units at the 2‐ and 8‐positions in a head‐to‐tail fashion by three‐fold SNAr reactions, giving rise to the characteristic N3O3 aza‐oxa‐crown architecture. o‐TQ can serve as a new tridentate nitrogen ligand to capture a CuI cation and adopt a bowl shape, before supramolecular complexation with corannulene and [12]cycloparaphenylene (CPP) occurs through π–π and CH–π interactions. In the presence of the CuI cation, the non‐emissive o‐TQ becomes a highly emissive material in the solid state, whereby the emission wavelengths depend on the ancillary ligand on the CuI cation. The o‐TQ/CuI complex is able to promote carbene catalysis to provide a range of enamines with a gem‐difluorinated terminus. [ABSTRACT FROM AUTHOR]

Low‐valent metal–organic frameworks (LVMOFs) and related materials have gained interest due to their potential applications in heterogeneous catalysis. However, of the few LVMOFs that have been reported, none have shown catalytic activity. Herein, a low‐valent metal‐organic material constructed from phosphine linkers and IrI nodes is reported. This material is effectively a crystalline, insoluble analogue of Vaska's complex. As such, the material reversibly binds O2 and catalyzes the reductive formation of enamines from amides. [ABSTRACT FROM AUTHOR]

We have demonstrated that the catalytic and enantioselective vinylcyclopropane‐cyclopentene rearrangement can be carried out on (vinylcyclopropyl)acetaldehydes through activation via enamine intermediates. The reaction makes use of racemic starting materials that, upon ring opening facilitated by the catalytic generation of a donor‐acceptor cyclopropane, deliver an acyclic iminium ion/dienolate intermediate in which all stereochemical information has been deleted. The final cyclization step forms the rearrangement product, showing that chirality transfer from the catalyst to the final compound is highly effective and leads to the stereocontrolled formation of a variety of structurally different cyclopentenes. [ABSTRACT FROM AUTHOR]

We report the first highly enantioselective construction of silicon‐stereocenters by asymmetric enamine catalysis. An unprecedented desymmetric intramolecular aldolization of prochiral siladials was thus developed for the facile access of multifunctional silicon‐stereogenic silacycles in high to excellent enantioselectivity. With an enal moiety, these adducts could be readily elaborated for the diverse synthesis of silicon‐stereogenic compounds, and for late‐stage modification. [ABSTRACT FROM AUTHOR]

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo‐ and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well‐developed. However, the efficient synthesis of chiral 3‐substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N‐aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5‐tricyclic lactone core structure of Speradine A. [ABSTRACT FROM AUTHOR]

The aggregation‐induced emission properties of tetraarylethenes (TAEs) have led to numerous applications in chemistry, biology, and materials science. Herein, we describe two fluorinated tetraarylethenes, which can be employed as universal tags for the synthesis of solid state luminogens. The tags are accessible in one or two steps from commercially available starting materials. Facile coupling reactions with ubiquitous substrates such as thiols, alcohols, amines, phosphines, aldehydes, and enamines allow preparing a wide range of TAE conjugates, including tagged amino acids, peptides, carbohydrates, steroids, and commercial polymers. [ABSTRACT FROM AUTHOR]

Asymmetric catalytic cascade processes offer direct access to complex chiral molecules from simple substrates and in a single step. In biocatalysis, cascades are generally designed by combining multiple enzymes, each catalyzing individual steps of a sequence. Herein, we report a different strategy for biocascades based on a single multifunctional enzyme that can promote multiple stereoselective steps of a domino process by mastering distinct catalytic mechanisms of substrate activation in a sequential way. Specifically, we have used an engineered 4‐oxalocrotonate tautomerase (4‐OT) enzyme with the ability to form both enamines and iminium ions and combine their mechanisms of catalysis in a complex sequence. This approach allowed us to activate aldehydes and enals toward the synthesis of enantiopure cyclohexene carbaldehydes. The multifunctional 4‐OT enzymes could promote both a two‐component reaction and a triple cascade characterized by different mechanisms and activation sequences. [ABSTRACT FROM AUTHOR]

The first catalytic enantioselective and diastereoselective synthesis of atropisomeric hydrazides was achieved using a sequential catalysis protocol. This strategy is based on a one‐pot sequence of two organocatalytic cycles featuring the enamine amination of branched aldehydes followed by nitrogen alkylation under phase‐transfer conditions. The resulting axially chiral hydrazides were obtained directly from commercially available reagents in high yields and with good stereocontrol. The permutation of organocatalysts allowed easy access to all stereoisomers, enabling a stereodivergent approach to enantioenriched atropisomeric hydrazides. [ABSTRACT FROM AUTHOR]

Central chirality in arene derivatives arising out of unsymmetrically substituted arene ring is a fascinating yet rarely explored research topic. Here, we report a desymmetrization approach to centrally chiral unfunctionalized arenes, which is enabled by the enantioselective de novo construction of the arene ring. This operationally simple protocol is based on a [4+2]‐cycloaddition between polycyclic meso‐cyclohexenediones and α,β‐unsaturated aldehydes, and doesn't usually require any external oxidant. Catalyzed by a diphenylprolinol silyl ether, this reaction proceeds via dienamine intermediate and greatly simplifies the access to diversely substituted chiral arenes with outstanding enantioselectivities. [ABSTRACT FROM AUTHOR]

Aromatic aldehydes are fundamental intermediates that are widely utilised for the synthesis of important materials across the broad spectrum of chemical industries. Accessing highly substituted derivatives can often be difficult as their functionalizations are generally performed via electrophilic aromatic substitution, SEAr. Here we provide an alternative and mechanistically distinct approach whereby aromatic aldehydes are assembled from saturated precursors via a desaturative process. This novel strategy harnesses the high‐fidelity of Diels–Alder cycloadditions to quickly construct multi‐substituted cyclohexenecarbaldehyde cores which undergo desaturation via the synergistic interplay of enamine, photoredox and cobalt triple catalysis. [ABSTRACT FROM AUTHOR]

Methyl diazoacetate reacts with 1‐(N‐pyrrolidino)cycloalkenes to give products of 1,3‐dipolar cycloadditions and azo couplings. The kinetics and mechanisms of these reactions were investigated by NMR spectroscopy and DFT calculations. Orthogonal π‐systems in the 1,3‐dipoles of the propargyl‐allenyl type allow for two separate reaction pathways for the (3+2)‐cycloadditions. The commonly considered concerted pathway is rationalized by the interaction of the enamine HOMO with LUMO+1, the lowest unoccupied orbital of the heteropropargyl anion fragment of methyl diazoacetate. We show that HOMO/LUMO(π*N=N) interactions between enamines and methyl diazoacetate open a previously unrecognized reaction path for stepwise cycloadditions through zwitterionic intermediates with barriers approximately 40 kJ mol−1 lower in energy in CHCl3 (DFT calculations) than for the concerted path. [ABSTRACT FROM AUTHOR]

An electrochemical method for the synthesis of unsymmetrically substituted NH‐pyrroles is described. The synthetic strategy comprises a challenging heterocoupling between two structurally diverse enamines via sequential chemoselective oxidation, addition, and cyclization processes. A series of aryl‐ and alkyl‐substituted enamines were effectively cross‐coupled from an equimolar mixture to synthesize various unsymmetrical pyrrole derivatives up to 84 % yield. The desired cross‐coupling was achieved by tuning the oxidation potential of the enamines by utilizing a "magic effect" of the additive trifluoroethanol (TFE). Additionally, extensive computational studies reveal the unique role of TFE in promoting the heterocoupling process by regulating the activation energies of the reaction steps through H‐bonding and C−H⋅⋅⋅π interactions. Importantly, the developed electrochemical protocol was found to be equally efficient for the homocoupling of enamines to form symmetric pyrroles up to 92 % yield. [ABSTRACT FROM AUTHOR]

Our ongoing search for underdeveloped functional group combinations has brought to light α‐fluorinated aminoalkylboronic acids, a new class of molecules featuring the B‐CF linkage. These compounds can now be generated from secondary amines and α‐boryl aldehydes through electrophilic fluorination of boryl enamines or enamides. Fluorinated β‐aminoalkylboronic acids show no signs of degradation under ambient conditions. We present evidence for the involvement of chair‐like motifs, favored over the acyclic forms by up to 1.7±0.1 kcal mol−1 in water and held together by an amine‐boronate hydrogen bond. Fluorinated β‐aminoalkylboronic acids are stable over a wide pH range and are characterized by a pKa of 3.4, which is the lowest of any alkylboronic acid. [ABSTRACT FROM AUTHOR]

A three‐component Lewis acid–base (Lewis trio) involving a bulky chiral primary amine, B(C6F5)3 and a bulky tertiary amine has been developed as an effective enamine catalyst for enantioselective disulfuration reactions. The bulky tertiary amine was found to activate a bulky primary–tertiary diamine–borane Lewis pair for enamine catalysis via frustrated interaction. The resulted chiral bulky Lewis trio (BLT) allows for the construction of chiral disulfides via direct disulfuration with β‐ketocarbonyls or α‐branched aldehydes in a practical and highly stereocontrolled manner. [ABSTRACT FROM AUTHOR]

In one pot, tertiary alkyl amines are oxidized to enamines by cationic dioxa[6]helicene, which further reacts as electrophile and oxidant to form mono or bis donor‐π‐acceptor coupling products. This original and convergent synthetic approach provides a strong extension of conjugation yielding chromophores that absorb intensively in far‐red or NIR domains (λmax up to 791 nm) and fluoresce in the NIR as well (λmax up to 887 nm). Intense ECD properties around 790 nm with a |Δϵ| value up to 60 M−1 cm−1 are observed. [ABSTRACT FROM AUTHOR]

Tris(pentafluorophenyl)borane has been found to catalyze the two‐fold C(sp3)−H silylation of various trialkylamine derivatives with dihydrosilanes, furnishing the corresponding 4‐silapiperidines in decent yields. The multi‐step reaction cascade involves amine‐to‐enamine dehydrogenation at two alkyl residues and two electrophilic silylation reactions of those enamines, one inter‐ and one intramolecular. [ABSTRACT FROM AUTHOR]

Tris(pentafluorophenyl)borane has been found to catalyze the two‐fold C(sp3)−H silylation of various trialkylamine derivatives with dihydrosilanes, furnishing the corresponding 4‐silapiperidines in decent yields. The multi‐step reaction cascade involves amine‐to‐enamine dehydrogenation at two alkyl residues and two electrophilic silylation reactions of those enamines, one inter‐ and one intramolecular. [ABSTRACT FROM AUTHOR]

An N‐heterocyclic‐carbene‐stabilized diboryne undergoes rapid, high‐yielding and catalyst‐free hydroamination reactions with primary amines, yielding 1‐amino‐2‐hydrodiborenes, which can be considered boron analogues of enamines. The electronics of the organic substituent at nitrogen influence the structure and further reactivity of the diborene product. With electron‐rich anilines, a second hydroamination can occur at the diborene to generate 1,1‐diamino‐2,2‐dihydrodiboranes. With isopropylamine, the electronic influence of the alkyl substituent upon the diborene leads to an unprecedented boron‐mediated intramolecular N‐dearylation reaction of an N‐heterocyclic carbene unit. [ABSTRACT FROM AUTHOR]

An enantioselective 1,4‐addition of α,β‐unsaturated carboxylic acids with cycloalkanones has been developed by using chiral amine–boronic acid cooperative catalysts. In the presence of a chiral amine and boronic acid, cycloalkanones and carboxylic acids are activated as chiral enamines and mixed anhydrides, respectively. The corresponding 1,4‐adducts are obtained in high yield with high enantioselectivity. Furthermore, subsequent oxylactonization of the 1,4‐adducts gives spirolactones with high diastereoselectivity. [ABSTRACT FROM AUTHOR]

Reported herein is a visible‐light‐mediated radical approach to the α‐alkylation of ketones. This method exploits the ability of a nucleophilic organocatalyst to generate radicals upon SN2‐based activation of alkyl halides and blue light irradiation. The resulting open‐shell intermediates are then intercepted by weakly nucleophilic silyl enol ethers, which would be unable to directly attack the alkyl halides through a traditional two‐electron path. The mild reaction conditions allowed functionalization of the α position of ketones with functional groups that are not compatible with classical anionic strategies. In addition, the redox‐neutral nature of this process makes it compatible with a cinchona‐based primary amine catalyst, which was used to develop a rare example of enantioselective organocatalytic radical α‐alkylation of ketones. [ABSTRACT FROM AUTHOR]

Unprecedented phosphine‐catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N‐based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one‐pot access to cyclopentenoyl enamines and imines, or (chiral) γ‐lactams through two geminal C−C bond or two C−N bond formations, respectively. Several P‐based key intermediates including a 1,4‐(bis)electrophilic α,β‐unsaturated ketenyl phosphonium species have been detected by 31P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram‐scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively. [ABSTRACT FROM AUTHOR]

The synthesis of three enamine hole‐transporting materials (HTMs) based on Tröger's base scaffold are reported. These compounds are obtained in a three‐step facile synthesis from commercially available materials without the need of expensive catalysts, inert conditions or time‐consuming purification steps. The best performing material, HTM3, demonstrated 18.62 % PCE in PSCs, rivaling spiro‐OMeTAD in efficiency, and showing markedly superior long‐term stability in non‐encapsulated devices. In dopant‐free PSCs, HTM3 outperformed spiro‐OMeTAD by a factror of 1.6. The high glass‐transition temperature (Tg=176 °C) of HTM3 also suggests promising perspectives in device applications. [ABSTRACT FROM AUTHOR]

The asymmetric formal hydroamination of enamines using a CuH catalyst is reported. The method provides a straightforward and efficient approach to the synthesis of chiral 1,2‐dialkyl amines in good yields with high levels of enantioselectivities for a broad range of substrates, and should have significant value for the preparation of molecules bearing a 1,2‐diamine motif. [ABSTRACT FROM AUTHOR]

The addition of 2,6‐dimethylphenyl isocyanide and t‐butyl isocyanide to tetramesityldisilene was examined. In both cases, the initially formed product is an iminodisilirane; however, the iminodisiliranes are unstable under the reaction conditions and react with a second equivalent of the isocyanide to give either a 3‐silaazetidine or a novel bicyclic double enamine, respectively. Taken together with the previous examples in the literature, the results demonstrate that subtle differences in the steric bulk of the disilene or the electronic effects of the isocyanide can lead to dramatic differences in the reaction pathway. Twice the fun: In the addition of 2,6‐dimethylphenyl isocyanide or tert‐butyl isocyanide to tetramesityldisilene, the initially formed product is an iminodisilirane. These iminodisilirane intermediates react with a second equivalent of the isocyanide to give a 3‐silaazetidine or a bicyclic double enamine, respectively. [ABSTRACT FROM AUTHOR]

The enantioselective N‐heterocyclic carbene catalyzed [3+3] annulation of α‐bromoenals by dynamic kinetic resolution (DKR) of enamines and normal resolution of α,α‐disubstituted imines were developed. The corresponding substituted dihydropyridones were isolated in good yields with excellent diastereo‐ and enantioselectivities, and a high selective factor (up to 83) was realized for the resolution of α,α‐disubstituted imines. The S factor: The enantioselective N‐heterocyclic carbene (NHC) catalyzed [3+3] annulation of α‐bromoenals by dynamic kinetic resolution (DKR) of enamines, and normal resolution of α,α‐disubstituted imines were developed. The corresponding substituted dihydropyridones were isolated in good yields with excellent diastereo‐ and enantioselectivities, and a high selectivity factor was realized for the resolution of α,α‐disubstituted imines. [ABSTRACT FROM AUTHOR]

Abstract: A multiresponsive enamine‐based molecular switch is presented, in which forward/backward configurational rotation around the C=C bond could be precisely controlled by the addition of an acid/base or metal ions. Fluorescence turn‐on/off effects and large Stokes shifts were observed while regulating the switching process with CuII. The enamine functionality furthermore enabled double dynamic regimes, in which configurational switching could operate in conjunction with constitutional enamine exchange of the rotor part. This behavior was used to construct a prototypical dynamic covalent switch system through enamine exchange with primary amines. The dynamic exchange process could be readily turned on/off by regulating the switch status with pH. [ABSTRACT FROM AUTHOR]

Abstract: The enantioselective intramolecular α‐arylation of cyclobutanones has been established by combining palladium and enamine catalyst systems. Two different enantioselective control strategies have been developed for cyclobutanone substrates bearing O‐ or N‐tethered aryl bromides. Further synthetic applications are also reported. [ABSTRACT FROM AUTHOR]

Abstract: A desymmetrizing dehydrogenation process catalyzed by a chiral primary amine is described herein. The reaction proceeds through the oxidation of a ketone enamine by IBX and enables the highly enantioselective desymmetrization of 4‐substituted cyclohexanones with the generation of chiral 4‐substituted cyclohexenones containing a remote γ‐stereocenter. [ABSTRACT FROM AUTHOR]

Abstract: A direct asymmetric Michael reaction of α,β‐unsaturated aldehydes and ketones proceeded in the presence of two pyrrolidine‐type catalysts, a diphenylprolinol silyl ether and hydroxyproline, to afford synthetically useful δ‐keto aldehydes with excellent diastereo‐ and enantioselectivity. Although there are several iminium ions and enamines in the reaction mixture, the iminium ion generated by the former catalyst reacts preferentially with the enamine generated by the latter catalyst. [ABSTRACT FROM AUTHOR]

The rational design and implementation of enantiodivergent enamine catalysis is reported. A simple secondary amine catalyst, 2-methyl- l-proline, and its tetrabutylammonium salt function as an enantiodivergent catalyst pair delivering the enantiomers of α-functionalized aldehyde products in excellent enantioselectivities. This novel concept of designed enantiodivergence is applied to the enantioselective α-amination, aldol, and α-aminoxylation/α-hydroxyamination reactions of aldehydes. [ABSTRACT FROM AUTHOR]

A short, 5-step total synthesis of (±)-3-demethoxyerythratidinone from a simple pyrrole derivative is described. Features include the formation of gram quantities of a key tricylic aziridine from a challenging photochemical cascade reaction through the use of flow photochemistry. The final step involved a highly unusual Heck cyclization whereby ligand control enabled efficient formation of the natural product in 69 % yield from the minor isomer present in an equilibrating mixture of labile enamines. [ABSTRACT FROM AUTHOR]

Detailed herein is the photochemical organocatalytic enantioselective α-alkylation of aldehydes with (phenylsulfonyl)alkyl iodides. The chemistry relies on the direct photoexcitation of enamines to trigger the formation of reactive carbon-centered radicals from iodosulfones, while the ground-state chiral enamines provide effective stereochemical control over the radical trapping process. The phenylsulfonyl moiety, acting as a redox auxiliary group, facilitates the generation of radicals. In addition, it can eventually be removed under mild reducing conditions to reveal methyl and benzyl groups. [ABSTRACT FROM AUTHOR]

The first example of organocatalyzed γ′-selective functionalization of cyclic enones with 3-substituted maleimides results in the stereoselective construction quaternary carbon center is presented. The reactions provided γ′-functionalized cyclic enones and β-functionalized cyclopentenones in good to excellent yields with excellent diastereo- and enantioselectivities. DFT calculations indicated that the reaction might proceed as a [4+2] cycloaddition/retro-Mannich reaction which could explain the unexpected product with a chiral quaternary carbon center and the excellent stereoselectivity. [ABSTRACT FROM AUTHOR]

A new approach for the divergent total syntheses of (±)-vincaminorine, (±)-N-methylquebrachamine, (±)-quebrachamine, (±)-minovine and (±)-vincadifformine, each in less than 10 linear steps starting from a single δ-lactam building block, is reported. Key to our route design is the late-stage generation of reactive enamine functionality from stable indole-linked δ-lactams via a highly chemoselective iridium(I)-catalyzed reduction. The efficiently formed secodine intermediates subsequently undergo either a formal Diels-Alder cycloaddition or a competitive Michael addition/reduction to access aspidosperma-type alkaloids in excellent diastereoselectivities. Product selectivity could be controlled by changing the indole N-protecting group in the reductive cyclization precursors. An asymmetric variant of this synthetic strategy for the synthesis of (+)-20-epi-ibophyllidine is also described. [ABSTRACT FROM AUTHOR]

Facile and effective access for the asymmetric construction of the useful and important skeleton of the bicyclic N,O-acetals is described. CuII/SaBOX could catalyze the reaction of β,γ-unsaturated α-ketoesters with cyclic enamines efficiently, thus affording the desired products in excellent yields with excellent stereoselectivities (21 examples; up to 99 % yields; up to >95:5 d.r.; and 95-99 % ee). This reaction can be well performed on gram scale, even with only 1 mol % catalyst loading. The single-crystal structures of the copper complexes lead to a good understanding of the stereo-synergistic effects of the sidearm. [ABSTRACT FROM AUTHOR]

1-Aminodecalins were prepared from acyclic precursors by combining the powerful twofold diene-transmissive Diels-Alder chemistry of [3]dendralenes with the simplicity of enamine formation. On mixing at ambient temperature, a simple dienal condenses with a primary or secondary amine to generate the enamine, a 1-amino-[3]dendralene in situ, and this participates as a double diene in a sequence of two Diels-Alder events with separate dienophiles. Overall, four C−C bonds and one C−N bond are formed. Mechanistic insights into these reactions are provided by means of density functional theory calculations. [ABSTRACT FROM AUTHOR]

A unique chemo- and regioselective α- and γ-arylation of palladium azapentadienyl intermediates is presented. Two distinct catalysts and sets of conditions successfully controlled the regioselectivity of the arylation. These methods provide the first umpolung C−H functionalization of azapentadienyl palladium intermediates and enable the divergent synthesis of allylic amine and enamine derivatives, which are of significant interest in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

A new method for CF3SO2Na-based direct trifluoromethylthiolation of C(sp²)[BOND]H bonds has been developed. CF3SSCF3 is generated in situ from cheap and easy-to-handle CF3SO2Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using RfSO2Na. [ABSTRACT FROM AUTHOR]

A silver-catalyzed amidiniumation of N-propiolic formamidines for the synthesis of novel enamine amido carbene precursors is reported. Isolation of a first silver intermediate in silver-catalyzed amidiniumation of alkynes and other organogold intermediates supports our proposed mechanisms. Several control experiments reveal the unexpected effects of both HOTf and substrate substituents on the choice of either a π or σ,π silver activation mode and the cyclization fashion. Bis(hydroxyimidazol)ium salts were obtained through an unprecedented umpolung of propiolamides. The byproduct Ag2O as either an oxidant or silver source promotes the syntheses of N-heterocyclic carbene (NHC) precursors or Ag/NHC complexes. [ABSTRACT FROM AUTHOR]

A general organocatalytic cross-dienamine activation strategy to produce chiral multifunctionalized norcamphor compounds having a large diversity in substitution pattern is presented. The strategy is based on a Diels-Alder reaction of an amino-activated cyclopentenone reacting with most common classes of electron-deficient olefins, such as nitro-, ester-, amide-, and cyano-substituted olefins, chalcones, conjugated malononitriles, CF3-substituted enones, and fumarates. The corresponding norcamphor derivatives are formed in good yield, excellent enantioselectivities, and with complete diastereoselectivity. Furthermore, it is demonstrated that quaternary stereocenters and spiro norcamphor compounds can be formed with high stereoselectivity. The present development provides a simple, direct, and efficient approach for the preparation of important norcamphor scaffolds. [ABSTRACT FROM AUTHOR]

The first organomediated asymmetric 18F fluorination has been accomplished using a chiral imidazolidinone and [18F]N-fluorobenzenesulfonimide. The method provides access to enantioenriched 18F-labeled α-fluoroaldehydes (>90 % ee), which are versatile chiral 18F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2 S,4 S)-4-[18F]fluoroglutamic acid. [ABSTRACT FROM AUTHOR]

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (−)-bursehernin. [ABSTRACT FROM AUTHOR]

The B(C6F5)3-catalyzed silylative reduction of conjugated nitriles has been developed to afford synthetically valuable β-silyl amines. The reaction is chemoselective and proceeds under mild conditions. Mechanistic elucidation indicates that it proceeds by rapid double hydrosilylation of the conjugated nitrile to an enamine intermediate which is subsequently reduced to the β-silyl amine, thus forming a new C(sp3)Si bond. Based on this mechanistic understanding, a preparative route to enamines was also established using bulky silanes. [ABSTRACT FROM AUTHOR]