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A new catalytic asymmetric tandem α‐alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N′‐dioxide/ZnII complexes. The proton shift preferentially proceeded instead of a silyl shift after α‐alkenyl addition of silyl enol ether to the ketimine. A wide range of β‐amino silyl enol ethers were synthesized in high yields with good to excellent ee values. Control experiments suggest that the Mukaiyama–Mannich reaction and tandem α‐alkenyl addition/proton shift reaction are competitive reactions in the current catalytic system. The obtained β‐amino silyl enol ethers were easily transformed into β‐fluoroamines containing two vicinal tetrasubstituted carbon centers. Surprise shift: An efficient route to β‐amino silyl enol ethers by an α‐alkenyl addition/proton shift sequence from silyl enol ethers to ketimines has been developed. Good enantioselectivities with a broad substrate scope were achieved using chiral N,N′‐dioxide/ZnII complexes. Deuterium‐labeling studies suggest that a key proton shift is involved in this reaction. [ABSTRACT FROM AUTHOR]

Reported herein is a rhodium(III)‐catalyzed three‐component annulation reaction of simple pyridines, alkynes, and 1,2‐dichloroethane (DCE), affording a streamlined pathway to diverse ring‐fused pyridiniums. DCE not only serves as a vinyl equivalent but also as an in situ activating agent for pyridine C2−H activation. A cationic five‐membered rhodacycle complex has been isolated and proposed as a possible intermediate. This strategy can be extended to other N‐containing heteroarenes for the synthesis of multiring‐fused pyridiniums. These multicomponent reactions exhibit excellent regioselectivity for 1,3‐diynes, paving a path to the cascade cyclization of 3‐fluoropyridine or N‐methylpyridin‐3‐amine with 1,3‐diynes for the construction of brand‐new tricyclic‐fused pyrano‐ or hydropyridoquinolizinium salts. These ionic fluorophores have been investigated as potential biomarkers. Triple agent: Disclosed herein is a rhodium(III)‐catalyzed multicomponent reaction of simple pyridines, alkynes, and 1,2‐dichloroethane (DCE) to afford a streamlined pathway to diverse ring‐fused pyridiniums. DCE serves as a vinyl equivalent and an in situ activating agent for pyridine C2−H activation, as well as a solvent. [ABSTRACT FROM AUTHOR]

Abstract: A novel gold‐catalyzed tandem protocol, initiated by hydride transfer in the presence of catalytic (C6F5)3PAuCl/AgSbF6, for the formation of fused polycyclic ring systems has been achieved. This tandem reaction provides rapid access to various fused polycyclic species in a single chemical operation, leading to stereospecific formation of two carbon–carbon bonds and three rings. [ABSTRACT FROM AUTHOR]

Abstract: Described here is a synthetic approach to access two of the most widely invoked cationic cobaltacycles in Cp*CoIII‐catalyzed C−H functionalization reactions by C−H activation. The unique stabilizing capability of MeCN was used to surmount the previously proposed reversible nature of the C−H metalation step. Moreover, it is revealed the boosting effect of 1,1,1,3,3,3‐hexafluoroisopropanol in the metalation step and in the reaction between N‐pyrimidinylindole and diphenylacetylene under catalytic conditions. [ABSTRACT FROM AUTHOR]

Abstract: A cascade Claisen rearrangement of a well‐organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported. This reaction features high atom economy (100 %), as well as catalyst‐free and gram‐scale conditions. Based on this novel methodology, the total synthesis of hemigossypol, gossypol, and their analogues has been realized. [ABSTRACT FROM AUTHOR]

A rhodium-catalyzed intramolecular acetyl-group transfer has been achieved through a 'cut and sew' process. The challenge arises from the existence of different competitive pathways. Preliminary success has been achieved with unstrained enones that contain a biaryl linker. The use of an electron-rich N-heterocycilc carbene (NHC) ligand is effective to inhibit undesired β-hydrogen elimination. Various 9,10-dihydrophenanthrene derivatives can be prepared with excellent functional-group compatibility. The 13C-labelling study suggests that the reaction begins with cleavage of the unstrained C−C bond, followed by migratory insertion and reductive elimination. [ABSTRACT FROM AUTHOR]

Reported herein is a light-triggered organocatalytic strategy for the desymmetrization of achiral 2-fluoro-substituted cyclopentane-1,3-diketones. The chemistry is based on an intermolecular aldol reaction of photochemically generated hydroxy- o-quinodimethanes and simultaneously forges two adjacent fully substituted carbon stereocenters, with one bearing a stereogenic carbon-fluorine unit. The method uses readily available substrates, a simple chiral organocatalyst, and mild reaction conditions to afford an array of highly functionalized chiral 2-fluoro-3-hydroxycyclopentanones. [ABSTRACT FROM AUTHOR]

A redox-neutral intermolecular dicarbofunctionalization of styrenes with CO2 at atmospheric pressure and carbon-centered radicals is described. This mild protocol results in multiple C−C bond-forming reactions from simple precursors in the absence of stoichiometric reductants, thus exploiting a previously unrecognized opportunity that complements existing catalytic carboxylation events. [ABSTRACT FROM AUTHOR]

Synthetically versatile 3,3-disubstituted fluorooxindoles exhibiting vicinal chirality centers were obtained in high yields and with excellent enantio-, diastereo-, and regioselectivity through catalytic asymmetric fluoroenolate alkylation with allylic acetates. The reaction proceeds under mild conditions and can be scaled up without compromising the asymmetric induction. The unique synthetic usefulness of the products is highlighted by the incorporation of additional functionalities and the formation of 3-fluorinated oxindoles exhibiting an array of four adjacent centers of chirality. A new C−F bond functionalization path that provides unprecedented possibilities for the stereoselective generation of a chiral quaternary carbon center in the alkaloid scaffold is introduced. [ABSTRACT FROM AUTHOR]

A new shelf-stable and easily scalable difluoromethylthiolating reagent S-(difluoromethyl) benzenesulfonothioate (PhSO2SCF2H) was developed. PhSO2SCF2H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl-difluoromethylthio difunctionalization of alkenes under mild reaction conditions. [ABSTRACT FROM AUTHOR]

We have developed a simple and convenient method for the cross-coupling of arylboronic acids and their derivatives with DAST-type reagents under mild and metal-free conditions to directly afford sulfinamides in moderate to good yields. Moreover, sulfonamides were obtained after a simple oxidation reaction. The reaction mechanism was investigated by 18O-labeling experiments, and the synthetic utility was demonstrated by the sulfoxidation of natural products. [ABSTRACT FROM AUTHOR]

Copper-catalyzed enantioselective allyl-allyl coupling between allylboronates and either Z-acyclic or cyclic allylic phosphates using a new chiral N-heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional SN2′-type regioselectivities and high enantioselectivities to deliver chiral 1,5-diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position. [ABSTRACT FROM AUTHOR]

The challenging synthesis of a laterally extended heptazethrene molecule, the super-heptazethrene derivative SHZ-CF3, is reported. This molecule was prepared using a strategy involving a multiple selective intramolecular Friedel-Crafts alkylation followed by oxidative dehydrogenation. Compound SHZ-CF3 exhibits an open-shell singlet diradical ground state with a much larger diradical character compared with the heptazethrene derivatives. An intermediate dibenzo-terrylene SHZ-2H was also obtained during the synthesis. This study provides a new synthetic method to access large-size quinoidal polycyclic hydrocarbons with unique physical properties. [ABSTRACT FROM AUTHOR]

Reported herein is a bifunctional-organocatalystmediated enantioselective inverse-electron-demand 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines with azlactones. The strategy provides concise access to enantioenriched C1-substituted tetrahydroisoquinolines featuring a pyrazolidinone scaffold. Moreover, the scalability and practical utility of this protocol was well demonstrated by employing a gram-scale reaction and some representative transformations. [ABSTRACT FROM AUTHOR]

We report a synthetic strategy for a chemoselective switch and a diastereo-divergent approach for the asymmetric reaction of 5 H-oxazol-4-ones and N-itaconimides catalyzed by l- tert-leucine-derived tertiary amine-urea compounds. The reaction was modulated to harness either tandem conjugate addition-protonation or [4+2] cycloaddition as major product with excellent enantio- and diastereoselectivities. Subjecting the enantio-enriched cycloaddition products to a basic silica gel reagent yields the diastereomer vis-à-vis the product directly obtained under conditions for addition-protonation, thus opening a diastereo-divergent route for creating 1,3-tertiary-hetero-quaternary stereocenters. Quantum chemical studies further provide stereochemical analysis for the [4+2] process and a plausible mechanism for this chemoselective switch is proposed. [ABSTRACT FROM AUTHOR]

A copper-catalyzed reaction of easily accessible a,a,a-trifluoromethylketones with various aldehydes affords difluoro-methylene compounds in the presence of diboron and NaOtBu. The key process of the reaction is the formation of a copper difluoroenolate by 1,2-addition of a borylcopper intermediate to a,a,a-trifluoromethylketones and subsequent β-fluoride elimination. Mechanistic studies including the isolation and characterization of a possible anionic copper alkoxide intermediate are also described. [ABSTRACT FROM AUTHOR]

An asymmetric [3+2] annulation reaction to form 3-pyrroline products is reported. Upon treatment with lithium diisopropylamide, readily available ethyl 4-bromocrotonate is deprotonated and trapped with Ellman imines selectively at the α-position to yield enantiopure 3-pyrroline products. This new method is compatible with aryl, alkyl, and vinyl imines. The efficacy of the method is showcased by short asymmetric total syntheses of (−)-supinidine, (−)-isoretronecanol, and (+)-elacomine. This novel annulation approach also works for an aldehyde, thus providing access to a 2,5-dihydrofuran product in a single step from simple precursors. By modifying the structure of the carbanion nucleophile, an asymmetric vinylogous aza-Darzens reaction can be realized. [ABSTRACT FROM AUTHOR]

In this Review we describe how the advent of machines is impacting on organic synthesis programs, with particular emphasis on the practical issues associated with the design of chemical reactors. In the rapidly changing, multivariant environment of the research laboratory, equipment needs to be modular to accommodate high and low temperatures and pressures, enzymes, multiphase systems, slurries, gases, and organometallic compounds. Additional technologies have been developed to facilitate more specialized reaction techniques such as electrochemical and photochemical methods. All of these areas create both opportunities and challenges during adoption as enabling technologies. [ABSTRACT FROM AUTHOR]

An unprecedented strategy for in situ generation of indole-based ortho-quinodimethanes ( oQDMs) from 2-methyl-3-alkylmethylindoles by either a metal-free DDQ- or BQ-mediated dehydrogenative process was developed. These oQDMs were trapped by electron-deficient dienophiles to provide a facile approach to synthetically valuable tetrahydrocarbazoles, carbazoles, and hetereoacenes. The salient features of this transformation include direct C(sp3)H bond functionalizations, readily available starting materials, metal-free conditions, high efficiency, operational simplicity, and ease of scale-up. [ABSTRACT FROM AUTHOR]

Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin-derived N-Cbz ketimines. The method requires only a low catalyst loading (2 mol%) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either TakemotoÏs catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/ cholecystokinin-B receptor antagonist AG-041R. [ABSTRACT FROM AUTHOR]

An efficient copper-promoted difluoromethylthiolation of aryl and heteroaryl diazonium salts is described. The reaction is conducted under mild reaction conditions and various functional groups were compatible. In addition, reactions of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a more practical one-pot direct diazotization and difluoromethylthiolation protocol was developed, and it converts the aniline derivatives into difluoromethylthiolated arenes. The utility of the method is demonstrated by difluoromethylthiolation of a number of natural products and drug molecules. [ABSTRACT FROM AUTHOR]

An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp3)H activation reactions. The first method led to the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities. [ABSTRACT FROM AUTHOR]

The unprecedented title reaction between glycine derivatives and indoles, as well as the auto-oxidative Povarov/aromatization tandem reaction of glycine derivatives with olefins are described. The reactions were performed in the absence of redox-active catalysts and chemical oxidants under mild reaction conditions. Only simple organic solvents and air (or O2) were required. [ABSTRACT FROM AUTHOR]

A regio-, diastereo-, and enantioselective [4+3] cycloaddition between vinylcarbenes and dienes has been achieved using the dirhodium tetracarboxylate catalyst [Rh2( S-BTPCP)4]. This methodology provides facile access to 1,4-cycloheptadienes that are regioisomers of those formed from the tandem cyclopropanation/Cope rearrangement reaction of vinylcarbenes with dienes. [ABSTRACT FROM AUTHOR]

A strategy for in situ generation of furan-based ortho-quinodimethanes ( o-QDMs) by the gold(I)-mediated dehydrogenative heterocyclization of 2-(1-alkynyl)-2-alken-1-ones in the presence of pyridine N-oxide under mild reaction conditions was developed. These in situ furan-based o-QDMs were trapped by electron-deficient olefins and alkynes, thus furnishing various 2,3-furan-fused carbocycles in good yields with high diastereo- and regioselectivities. [ABSTRACT FROM AUTHOR]

The highly efficient and diastereoselective synthesis of E dienes has been accomplished through radical cyclization of bromoallyl hydrazones. This methodology has been further extended to generate these products through a one-pot condensation/radical cyclization/cycloreversion cascade from simple aldehyde starting materials in high yields (>75 %) and high diastereoselectivities (>95:5). Mechanistic investigations suggest that the cascade reaction proceeds through a cyclic diazene intermediate prior to the cycloreversion. [ABSTRACT FROM AUTHOR]

Catalytic asymmetric Friedel-Crafts alkylation is a powerful protocol for constructing a chiral C(sp2)C(sp3) bond. Most previous examples rely on LUMO activation of the electrophiles using chiral catalysts with subsequent attack by electron-rich arenes. Presented herein is an alternative strategy in which the HOMO of the aromatic π system of 2-furfuryl ketones is raised through the formation of a formal trienamine species using a chiral primary amine. Exclusive regioselective alkylation at the 5-position occurred with alkylidenemalononitriles, and high reactivity and excellent enantioselectivity (up to 95 % ee) was obtained by this remote activation. [ABSTRACT FROM AUTHOR]

The alkenylation reactions of 8-methylquinolines with alkynes, catalyzed by [{Cp*RhCl2}2], proceeds efficiently to give 8-allylquinolines in good yields by C(sp3)H bond activation. These reactions are highly regio- and stereoselective. A catalytically competent five-membered rhodacycle has been structurally characterized, thus revealing a key intermediate in the catalytic cycle. [ABSTRACT FROM AUTHOR]

The first example of C alkylation of 1,2-dihydropyridines with alkyl triflates and Michael acceptors was developed to introduce quaternary carbon centers with high regio- and diastereoselectivity. Hydride or carbon nucleophile addition to the resultant iminium ion also proceeded with high diastereoselectivity. Carbon nucleophile addition results in an unprecedented level of substitution to provide piperidine rings with adjacent tetrasubstituted carbon atoms. [ABSTRACT FROM AUTHOR]

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives. [ABSTRACT FROM AUTHOR]

Di- and polyboron (hetero)arenes, site-differentiated with MIDA boronyl (MIDA= N-methyliminodiacetic acid) and pinacolato boronyl (Bpin), were prepared by an iridium-catalyzed direct CH borylation of readily available (hetero)aryl MIDA boronates. The excellent synthetic uses of these multisite nucleophiles were demonstrated by the high-yield production of a variety of multifunctionalized poly(hetero)arenes with the highly chemoselective Suzuki-Miyaura coupling (SMC) of the Bpin moiety being an essential step. [ABSTRACT FROM AUTHOR]

Three‐star compounds: The title reaction of β‐ketoamides, acrolein, and aminophenols, catalyzed by a bifunctional thiourea‐tertiary amine organocatalyst, enables the preparation of an enantioenriched diazabicyclo[2.2.2]octanone (2,6‐DABCO) scaffold. The chemoselective reaction sequence installs five new bonds and three stereocenters, two of which are contiguous tetrasubstituted centers, with excellent yields and high levels of stereocontrol. M.S.=molecular sieves. [ABSTRACT FROM AUTHOR]

Newly framed: The δ,ε CC bond of an interrupted cyclic 2,5‐dienone induces the formation of a linear trienamine in the presence of a chiral primary amine, thus enabling the δ,ε‐CC bond to participate in a highly asymmetric inverse‐electron‐demand aza‐Diels–Alder (DA) reaction with electron‐deficient 1‐azadienes. The DA reaction can be coupled with a Michael addition to produce a polycyclic framework with complete stereocontrol. [ABSTRACT FROM AUTHOR]

Strain for an effect: The cross‐coupling reaction of highly strained tetrahedranes with aryl halides has been investigated. In the presence of a palladium catalyst, tetrahedryllithium rapidly reacted with various aryl halides to form aryl‐substituted tetrahedranes (see picture) in good to excellent yields. The UV/Vis absorption spectra suggest an extended σ–π conjugation between the σ orbital of the tetrahedrane core and the aryl π system. [ABSTRACT FROM AUTHOR]

New tricks, old reaction: The title reaction proceeds under mild and transition‐metal‐free conditions (see scheme; Tf=trifluoromethanesulfonyl). Various combinations of substrates are applicable to the synthesis of γ,δ‐unsaturated ketones by employing silicon substituents at the β‐position of the enones. The silicon substituents play a key role in stabilization of the cationic intermediate by hyperconjugation. [ABSTRACT FROM AUTHOR]

The article presents a study which examines a radical trifluoromethylation of olefins through applying the Langlois reagent. It notes that unactivated olefins have been used as the starting materials. It states that using an olefin as the synthetic precursor instead of a preformed substrate makes the method advantageous. It mentions that mild reaction conditions, wide functional-group tolerance, and the use of an inexpensive trifluoromethylating agent are the main features of the reaction.

But(yl) not futile: A range of N‐tert‐butyl‐substituted triazolylidene N‐heterocyclic carbenes have been prepared. Of these, the morpholinone‐derived catalyst (1) proved best suited to the enantioselective synthesis of cyclopentanes from donor–acceptor cyclopropanes and α,β‐unsaturated acyl fluorides. The performance of this catalyst has been correlated to the electronic nature of the catalyst by 13C NMR analysis. M.S.=molecular sieves, TMS=trimethylsilyl. [ABSTRACT FROM AUTHOR]

Cracked under strain: Strained allylic cyclobutanols and cyclopropanols readily undergo a ring expansion described by the title rearrangement. This reaction is promoted by catalytic amounts of 1 and displays high tolerance with respect to the substrate scope. The corresponding β‐fluoro spiroketone products are isolated in high yields and with excellent stereoselectivities. EDG=electron‐donating group, EWG=electron‐withdrawing group. [ABSTRACT FROM AUTHOR]

A directed cross-aldol reaction of silyl enol ethers with carbonyl compounds, such as aldehydes and ketones, promoted by a Lewis acid, a reaction which is now widely known as the Mukaiyama aldol reaction. It was first reported in 1973, and this year marks the 40th anniversary. The directed cross-aldol reactions mediated by boron enolates and tin(II) enolates also emerged from the Mukaiyama laboratory. These directed cross-aldol reactions have become invaluable tools for the construction of stereochemically complex molecules from two carbonyl compounds. This Minireview provides a succinct historical overview of their discoveries and the early stages of their development. [ABSTRACT FROM AUTHOR]

Enantioselectivity through H bonding: An unprecedented [4+3] annulation of enals with o‐quinone methides catalyzed by N‐heterocyclic carbenes (NHCs) to give benzo‐ε‐lactones is described. High to excellent enantioselectivity was achieved by using a chiral triazolium NHC having a free OH group, which participates in a hydrogen‐bonding interaction with the substrate. [ABSTRACT FROM AUTHOR]

High turnover: An highly efficient catalytic asymmetric hydrogenation of δ‐aryl‐δ‐ketoesters has been realized by using the chiral spiroiridium catalyst (R)‐1. Chiral 1,5‐diol products are obtained with excellent enantioselectivity and turnover numbers (TONs) as high as 100 000. TOF=turnover frequency. [ABSTRACT FROM AUTHOR]

Striking gold: A series of variously functionalized propynyl arenes was smoothly converted into indan‐2‐ones by a new gold(I)‐catalyzed oxidative cyclization process. [LAu]NTf2 (Tf=trifluoromethanesulfonyl) is a superior catalyst both in terms of yield and kinetics for the present transformation. [ABSTRACT FROM AUTHOR]

Automated falling-solid flash vacuum pyrolysis allows the rapid and efficient synthesis of a variety of arylacetylenes from 4-arylmethylidene-5(4H)-isoxazolone derivatives, which were prepared from aldehyde precursors. The acetylenes are readily obtained in multigram quantities. [ABSTRACT FROM AUTHOR]