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Herein, we report a synthesis of cyclohexanones bearing multi‐continuous stereocenters by combining copper‐catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium‐catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction of adjacent stereocenters (1,2‐position) reported in the literature, the current reaction can achieve the stereodivergent construction of nonadjacent stereocenters (1,3‐position) by a proper combination of two chiral catalysts with different enantiomers. [ABSTRACT FROM AUTHOR]

Cascade Synthesis In their Full Paper on page 16810 ff., K. A. Jørgensen et al. present a novel enantioselective strategy for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine structures, based on a pair of divergent reaction pathways in which hydroxyarenes react with γ ‐ keto ‐ α,β ‐ unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway leads to chiral 5,5 ‐ fused acetals, the tetrahydrofurobenzofuran scaffolds, with two stereocenters, whereas the other reaction pathway provides 5,6 ‐ bridged methanobenzodioxepine scaffolds with three stereocenters. The reaction can proceed with catalyst loadings as low as 0.25 mol %, giving among the highest known turnover numbers in iminium ion catalysis. [ABSTRACT FROM AUTHOR]

Azairidacycles derived from protic benzylamines have been utilized as powerful hydrogen ‐ transfer catalysts for ketones and alcohols. The chiral amidoiridium complexes are accessible from (R) ‐ 5 ‐ amino ‐ 6,7,8,9 ‐ tetrahydro ‐ 5H ‐ benzocycloheptene and (R) ‐ 1 ‐ phenyl ‐ 2,2 ‐ dimethylpropylamine, whereas O ‐ silylated (S) ‐ 2 ‐ amino ‐ 2 ‐ phenylethanols afford amido ‐ bridged dimers. The preferable catalytic performance of the mononuclear complexes corroborates that the 16 ‐ electron structure is vital for the smooth H+/H– transfer based on the metal/NH cooperative effect. More information can be found in the Full Paper by Yoshihito Kayaki, Takao Ikariya et al. on page   2924 in Issue 20, 2016 (DOI: 10.1002/asia.201600955). [ABSTRACT FROM AUTHOR]

Reaction‐based mechanistic investigations were performed for the asymmetric hetero‐Diels–Alder reactions of enones with isatins catalyzed by an amine‐based three‐component catalyst system. The reaction route was likely a kinetically controlled [4+2] cycloaddition reaction of the in situ‐generated enamine of the enone as the diene and isatin as the dienophile. All three components of the catalyst system played important roles for the catalysis and the stereocontrol. More information can be found in the Full Paper by F. Tanaka and co‐workers on page 153 in Issue 1, 2016 (DOI: 10.1002/ajoc.201500412). [ABSTRACT FROM AUTHOR]

Organocatalysis in Medicinal Chemistry A flexible and simple organocatalytic cascade reaction, involving a Michael ‐ amination ‐ hemiaminalization relay, has been developed for constructing a chiral hexahydropyridazine scaffold. In their Full Paper on page 18100 ff., C. Peng, G. He, B. Han et al. demonstrate that several compounds synthesized by this method show promising antiproliferative activity in breast cancer cell cultures. Mechanistic studies performed on one of these compounds suggest that they exert the anticancer effects by inducing apoptosis through extracellular signal related kinase (ERK) ‐ and poly(adenosine diphosphate ribose) polymerase (PARP) ‐ regulated pathways, as well as mitochondrial pathways. [ABSTRACT FROM AUTHOR]

An N‐heterocyclic carbene (NHC) catalyzed asymmetric [3+3] annulation of α‐bromoenals with 5‐aminopyrazoles is described. Using the established methodology, a structurally diverse set of high value dihydropyrazolo[3,4‐b]pyridine‐6‐ones were efficiently constructed in high yields (up to 99%) with excellent enantioselectivities (up to >99%). The easily available starting materials, broad substrate scope, mild reaction conditions, excellent yield and enantioselectivity make this strategy attractive for the asymmetric construction of pyrazolo‐fused pyridone derivatives. [ABSTRACT FROM AUTHOR]

The stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2−Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT). [ABSTRACT FROM AUTHOR]

Trifluoromethyl‐bearing 5‐membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp3)−H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium‐catalyzed α‐CF3‐α‐alkyl carbene insertion into C(sp3)−H bonds of a broad range of substrates to access 7 types of CF3‐bearing saturated 5‐membered carbo‐ and heterocycles. The reaction is particularly effective for benzylic C−H insertion exerting good site‐, diastereo‐ and enantiocontrol, and applicable to the synthesis of chiral CF3 analogues of bioactive molecules. Ruthenium α‐CF3‐α‐alkyl carbene complexes underwent stoichiometric reactions to give C−H insertion products, lending evidence for the involvement of metal α‐CF3‐α‐alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra‐carbene C−H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C−H insertion reactions. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed site‐ and stereoselective C−H activation of strained (hetero)cycloalkanes remains a formidable challenge. We herein report a carbamate‐directed iridium‐catalyzed asymmetric β−C(sp3)−H borylation of cyclopropanol derivatives. A variety of densely functionalized cyclopropanols were obtained in good enantioselectivities via desymmetrization and kinetic resolution. In addition, site‐selective C(sp3)−H borylation of methine groups furnished α‐borylated (hetero)cycloalkanols in moderate to good yields. The synthetic utility of the method was further shown in a gram‐scale synthesis and diverse downstream transformations of borylated products. [ABSTRACT FROM AUTHOR]

Alkynes and 1,3‐dienes are among the most readily available precursors for organic synthesis. We report two distinctly different, catalyst‐dependent, modes of regio‐ and enantioselective cycloaddition reactions between these classes of compounds providing rapid access to highly functionalized 1,4‐cyclohexadienes or cyclobutenes from the same precursors. Complexes of an earth abundant metal, cobalt, with several commercially available chiral bisphosphine ligands with narrow bite angles catalyze [4+2]‐cycloadditions between a 1,3‐diene and an alkyne giving a cyclohexa‐1,4‐diene in excellent chemo‐, regio‐ and enantioselectivities. In sharp contrast, complex of a finely tuned phosphino‐oxazoline ligand promotes unique [2+2]‐cycloaddition between the alkyne and the terminal double bond of the diene giving a highly functionalized cyclobutene in excellent regio‐ and enantioselectivities. [ABSTRACT FROM AUTHOR]

Diaryl ethers are widespread in biologically active compounds, ligands and catalysts. It is known that the diaryl ether skeleton may exhibit atropisomerism when both aryl rings are unsymmetrically substituted with bulky groups. Despite recent advances, only very few catalytic asymmetric methods have been developed to construct such axially chiral compounds. We describe herein a dynamic kinetic resolution approach to axially chiral diaryl ethers via a Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes with anilines. The desired diaryl ethers could be obtained in moderate to good chemical yields (up to 79 %) and high enantioselectivities (up to 95 % ee) under standard reaction conditions. Such structural motifs are interesting precursors for further transformations and may have potential applications in the synthesis of chiral ligands or catalysts. [ABSTRACT FROM AUTHOR]

Axially chiral compounds with a rotation restricted N−C bond are of great importance in synthetic chemistry, pharmaceuticals, and material sciences. The search for efficient and selective routes for the synthesis of these frameworks is of great interest and importance. We herein disclose an iridium‐catalyzed asymmetric C−H borylation protocol for the enantioselective synthesis of chiral N‐aryl phthalimides. The current method features good compatibility of functional groups, broad substrate scope, and high enantioselectivities. We also demonstrate the synthetic utility on a gram‐scale C−H borylation for diverse C−B bond transformations, including the preparation of a chiral catalyst for asymmetric catalysis. [ABSTRACT FROM AUTHOR]

A copper‐catalyzed regio‐ and diastereoselective borylacylation of α,β‐unsaturated esters with B2pin2 and acyl fluorides has been developed to afford the β'‐boryl‐β‐ketoesters with high anti‐diastereoselectivity (up to >99 : 1). Additionally, the borylcarbamoylation is possible by using isocyanates as electrophiles instead of acyl fluorides. Moreover, the enantioselective borylacylation and borylcarbamoylation are also achieved by judicious choice of a chiral phosphoramidite‐ligated copper complex. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed enantioselective C−H activation of prochiral sulfoximines for non‐annulated products remains a formidable challenge. We herein report iridium‐catalyzed enantioselective C−H borylation of N‐silyl diaryl sulfoximines using a well‐designed chiral bidentate boryl ligand with a bulky side arm. This method is capable of accommodating a broad range of substrates under mild reaction conditions, affording a vast array of chiral sulfoximines with high enantioselectivities. We also demonstrated the synthetic utility on a preparative‐scale C−H borylation for diverse downstream transformations, including the synthesis of chiral version of bioactive molecules. Computational studies showed that the bulky side arm of the ligand confers high regio‐ and enantioselectivity through steric effect. [ABSTRACT FROM AUTHOR]

Chiral α‐substituted ethylphosphonate and ethylphosphine oxide compounds are widely used in drugs, pesticides, and ligands. However, their catalytic asymmetric synthesis is still rare. Of the only asymmetric hydrogenation methods available at present, all cases use rare metal catalysts. Herein, we report an efficient earth‐abundant transition‐metal nickel catalyzed asymmetric hydrogenation affording the corresponding chiral ethylphosphine products with up to 99 % yield, 96 % ee (enantiomeric excess) (99 % ee, after recrystallization) and 1000 S/C (substrate/catalyst); this is also the first study on the asymmetric hydrogenation of terminal olefins using a nickel catalyst under a hydrogen atmosphere. The catalytic mechanism was investigated via deuterium‐labelling experiments and calculations which indicate that the two added hydrogen atoms of the products come from hydrogen gas. Additionally, it is believed that the reaction involves a NiII rather than Ni0 cyclic process based on the weak attractive interactions between the Ni catalyst and terminal olefin substrate. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: NiH‐catalyzed multicomponent reductive hydrofunctionalization of alkenes is an attractive but poorly explored approach to rapidly increasing molecular complexity. In this process, the selective generation of the desired product can be challenging. Herein, we report that a highly chemo‐, regio‐ and enantioselective reductive hydrocarbonylation of alkenes has been achieved using a chloroformate ester as a source of CO. A wide range of structurally diverse α‐hydroxy ketones, privileged structural elements in bioactive molecules and useful building blocks, were obtained from such reactions with high enantiomeric purity. [ABSTRACT FROM AUTHOR]

We describe an iron‐catalyzed asymmetric oxidative C−C coupling of diarylamines which proceeds at room temperature with air as final oxidant. Using hexadecafluorophthalocyanine‐iron(II) as catalyst in the presence of catalytic amounts of an axially chiral biaryl phosphoric acid, the resulting chiral 2,2′‐diamino‐1,1′‐biaryls are obtained in up to 90 % ee as confirmed by chiral HPLC. A detailed mechanism has been proposed with a radical cation‐chiral phosphate ion pair as key intermediate leading to the observed asymmetric induction. [ABSTRACT FROM AUTHOR]

A base‐promoted tandem Michael addition of malonates to 2,3‐ bis(diarylphosphinyl)‐1,3‐butadienes was developed for the synthesis of cyclopentyl 1,2‐bisphosphine compounds. This method enables rapid construction of various 1,2‐bis(diarylphosphinyl)cyclopentanes, and features readily accessible reactants, mild conditions and good functional group tolerance. The product could be easily transformed to the corresponding transition metal complexes, which may find broad applications in asymmetric catalysis. [ABSTRACT FROM AUTHOR]

The discovery of enantioselective desymmetrization reactions to provide practical synthesis of enantio‐enriched atropisomeric biaryls is a challenging topic in the field of asymmetric catalysis. Herein, we report a highly enantioselective desymmetrization reaction for the synthesis of axially chiral biaryl N‐oxides by atroposelective C−H iodination by using Pd(II) coordinated by N‐benzoyl‐l‐phenylalanine as a chiral catalyst at room temperature. A broad range of products were obtained in high yields (up to 99 %) with excellent enantioselectivities (up to 98 % ee). The products could be synthesized in gram scale, one of which was proved to be a powerful organocatalyst in asymmetric allylation reaction. Mechanistic evidence as well as DFT calculations point towards the factors that lead to high reactivity and excellent enantiocontrol in this reaction. [ABSTRACT FROM AUTHOR]

Satoh–Miura reaction is an important method for extending π‐systems by forging multi‐substituted benzene rings via double aryl C−H activation and annulation with alkynes. However, the development of highly enantioselective Satoh–Miura reaction remains rather challenging. Herein, we report an asymmetric Satoh–Miura reaction between 1‐aryl benzo[h]isoquinolines and internal alkynes enabled by a SCpRh‐catalyst. Judiciously choosing the counteranion of the Rh‐catalyst is crucial for the desired reactivity over the competitive formation of azoniahelicenes. Detailed mechanistic studies support the proposal of counteranion‐directed switching of reaction pathways in Rh‐catalyzed asymmetric C−H activation. [ABSTRACT FROM AUTHOR]

An enantioselective phosphine‐catalyzed [3+2] cycloaddition between aza‐aurones and allenoates is here described. The reaction proceeded under mild reaction conditions to afford 2‐spirocyclopentyl indolin‐3‐one derivatives as single γ‐isomer and with high levels of stereocontrol. [ABSTRACT FROM AUTHOR]

Electronically matched nucleophilic 1,6‐conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5‐conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5‐conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5‐conjugate reaction, followed by inter‐ or intramolecular [3+2] cyclization. A migratory 1,5‐addition protocol is established to corroborate the feasibility of this umpolung concept. The 1,5‐addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis. [ABSTRACT FROM AUTHOR]

Chiral imidodiphosphates (IDPs) have emerged as strong Brønsted acid catalysts for many enantioselective processes. However, the dynamic transformation between O,O‐syn and O,O‐anti conformers typically results in low enantioselectivity. Here we demonstrate that topologies of metal‐organic frameworks (MOFs) can be exploited to control IDP conformations and local chiral microenvironments for enantioselective catalysis. Two porous Dy‐MOFs with different topologies are obtained from an enantiopure 1,1′‐biphenol IDP‐based tetracarboxylate ligand. While the ligand adopts a 4‐ or 3‐connected (c) binding mode, all IDPs are rigidified to get only a single O,O‐syn conformation and display greatly enhanced Brønsted acidity relative to the free IDP. The MOF with the 4‐c IDP that has a relatively less compact shape than the 3‐c IDP can be an efficient and recyclable heterogeneous Brønsted acid catalysing the challenging asymmetric O,O‐acetalization reaction with up to 96 % enantiomeric excess. [ABSTRACT FROM AUTHOR]

The copper‐catalyzed enantioconvergent radical C(sp3)−C(sp2) cross‐coupling of tertiary α‐bromo‐β‐lactams with organoboronate esters could provide the synthetically valuable α‐quaternary β‐lactams. The challenge arises mainly from the construction of sterically congested quaternary stereocenters between the tertiary alkyl radicals and chiral copper(II) species. Herein, we describe our success in achieving such transformations through the utilization of a copper/hemilabile N,N,N‐ligand catalyst to forge the sterically congested chiral C(sp3)−C(sp2) bond via a single‐electron reduction/transmetalation/bond formation catalytic cycle. The synthetic potential of this approach is shown in the straightforward conversion of the corresponding products into many valuable building blocks. We hope that the developed catalytic cycle would open up new vistas for more enantioconvergent cross‐coupling reactions. [ABSTRACT FROM AUTHOR]

Herein we report the first method for highly enantioselective Brønsted acid catalyzed Heyns rearrangements. These reactions, catalyzed by a chiral spiro phosphoric acid, afforded synthetically valuable chiral α‐aryl‐α‐aminoketones which cannot be obtained by means of previously reported Heyns rearrangement methods. This method features low catalyst loadings, high yields and high enantioselectivities, making these reactions highly practical. We used the method to efficiently synthesize various chiral amines, including some biologically active molecules. We experimentally proved that these acid‐catalyzed Heyns rearrangements proceeded via a proton‐transfer process involving an enol intermediate and the stereocontrol was realized during the proton‐transfer step. [ABSTRACT FROM AUTHOR]

Isothiazole units exist in many natural products and pharmaceutics. Up to now, construction of isothiazole‐containing axially chiral biaryls has not been reported yet. Herein we disclose a chiral phosphoric acid catalyzed atropoenantioselective arylation of 5‐amino‐isothiazoles with methyl p‐quinone carboxylate. Various novel isothiazole‐containing axially chiral biaryls were achieved in moderate to good yields (up to 95%) with generally moderate to good enantioselectivities (up to 90% ee). In addition, the structure of one product was determined by an X‐ray crystal structural analysis and a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Chiral bis‐oxalamide (CBOA)/rare‐earth metal complexes‐catalyzed asymmetric inverse‐electron‐demand oxa‐hetero‐Diels‐Alder (HDA) reactions were investigated under mild reaction conditions, which was performed between β,γ‐unsaturated α‐ketoesters and various electron‐riched dienophiles, such as cyclopentadiene, 2,3‐dihydrofuran, 3,4‐dihydro‐2H‐pyran, tetrahydropyridine as well as phenyl(vinyl)sulfane. Several series of optically active functionalized 3,4‐dihydro‐2H‐pyran or ring fused dihydropyran derivatives were obtained in high yields with high diastereo‐ and enantioselectivity. The procedure was able to tolerate a relatively wide range of substrates. The coordination mode of chiral bis‐oxalamide with Sc(III) was demonstrated by the X‐ray crystallographic structure, and DFT calculations were carried out to uncover the regio‐ and stereocontrol. [ABSTRACT FROM AUTHOR]

Strategies on the construction of enantiomerically pure silicon‐stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh‐catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with "silicon‐centered" racemic hydrosilanes that enables the facile preparation of silicon‐stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non‐diastereopure‐type mixed phosphine‐phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the SN2 substitution of chloride ion to realize the chiral inversion of silicon center. [ABSTRACT FROM AUTHOR]

The structure of in situ generated chiral aryl‐λ3‐iodanes obtained under oxidative reaction conditions was not yet observable with experimental techniques and their proposed structures are purely based on DFT calculations. Herein, we establish vibrational circular dichroism (VCD) spectroscopy as an experimental technique to verify DFT‐calculated chiral iodane structures. Based on a chiral triazole‐substituted iodoarene catalyst, we were able to elucidate a yet undescribed cationic chiral iodane as the most populated intermediate under oxidative conditions with a significant intramolecular N−I‐interaction and no significant interactions with tosylate or m‐chlorobenzoic acid as potential anionic ligands. Instead, aggregation of these substrates was found, which resulted in the formation of a non‐coordinating anionic hydrogen bonded complex. The importance of VCD as a crucial experimental observable is further highlighted by the fact that our initial structural proposal, that was purely based on DFT calculations, could be falsified. [ABSTRACT FROM AUTHOR]

Herein, we report the catalytic 1,6‐addition of chiral alkyl copper nucleophiles, in‐situ generated from borylalkenes and a copper‐hydride catalyst under mild conditions. Chemo‐ and stereoselective control was crucial in this reductive coupling process of borylalkenes and para‐quinone methides, sequentially forming adjacent stereogenic centers with good diastereo‐ and enantioselectivity. Through the multicomponent and catalytic tandem reactions, asymmetric 1,6‐adducts of p‐quinone methides were efficiently synthesized. [ABSTRACT FROM AUTHOR]

Although there is an abundance of methods for the enantioselective synthesis of 2‐isoxazolines and 2‐isoxazolin‐5‐ones, relatively few of these approaches have been reported when these heterocycles bear fully substituted stereocenters. In this review, we will detail the methods that have been used to successfully accomplish these challenging asymmetric transformations and give insights into their importance, such as allowing access to unique three‐dimensional chemical space. The limitations of the currently known reactions will be discussed, as well as highlighting the future developments needed to advance the research field. [ABSTRACT FROM AUTHOR]

Since the first report of bifunctional sulfonamide organocatalysts in 2004, these chiral compounds have proven to be a reliable hydrogen‐bonding catalyst and have been wildly employed in asymmetric organocatalysis due to its strong acidity and self‐aggregation‐free property. Herein, we review the application of bifunctional sulfonamide as hydrogen‐bonding catalyst after 2011, and our highlights will cover asymmetric process including aldol reaction, Michael addition, Mannich reaction, desymmetrization and cyclization. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The direct addition of aryl C—H bond to carbon‐heteroatom double bond by transition‐metal‐catalyzed C—H activation has been extensively investigated in the past decade. However, the enantioselective intermolecular C—H addition to aldehyde has not yet been reported and is of significant challenge. Rh(III)‐catalyzed highly enantioselective intermolecular C—H addition of aryl oxime ethers to glyoxylates is reported. Chiral mandelic acid esters were obtained in excellent yields (up to 98%) and enantioselectivity (up to 99% ee) in the presence of a chiral CpRh(III) catalyst under mild conditions. The substituents on the Cp ring and BINOL skeleton were responsible for the high enantioselectivity observed. The method displays a broad substrate scope and good functionality tolerance. These results provide not only a promising C—H addition approach but also a proof of concept for developing broader asymmetric C—H addition reactions. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The direct conversion of unactivated alkanes and cycloalkanes into structurally diverse molecules through aliphatic C—H functionalization is a useful process, which has attracted intense interest from academia and industry. Methods to control chemo‐ and site‐selectivity, combined with asymmetric catalysis, provide appealing access to high value‐added enantiomer‐enriched compounds but are far less developed. This review focuses on recent progress in (i) asymmetric reactions of alkanes or cycloalkanes with prochiral substrates which generate a stereocenter adjacent to the cleaved C(sp3)–H bond, and (ii) C(sp3)–H enantiodiscriminatory reactions creating a new stereogenic center on the carbon of a cleaved C(sp3)–H bond. Elegant strategies are discussed, including (a) metal carbene‐induced C—H insertions by chiral rhodium catalysts, (b) metal‐oxo‐mediated C—H oxidation by biomimetic manganese catalysts, (c) enzyme catalysis by cytochromes P450 variants, and (d) dual catalysis by a photocatalyst and a chiral Lewis acid (CLA) or a chiral phosphoric acid (CPA). These catalytic systems can not only precisely recognize primary, secondary and tertiary C—H bonds at specific positions in alkanes and cycloalkanes, but also support a high level of stereoselectivity in the reactions. It is expected that the advances will stimulate further progress in asymmetric catalysis, synthetic methodology, pharmaceutical development and industrial processes. [ABSTRACT FROM AUTHOR]

The observation of the active species is the goal of most spectroscopic investigations on enantioselective organocatalysts in solution. Although NMR spectroscopy is widely applied, it has low sensitivity for conformational changes or the chiral nature of the interactions. In the present work, we exemplify the use of vibrational circular dichroism (VCD) spectroscopy for the characterization of a chiral thiourea model compound in nonpolar and polar solvents, as well as for a detailed analysis of its interaction with a model reactant. We discuss solvent-induced conformational changes of the thiourea, and provide evidence for an unexpected binding topology between the thiourea and an acetate anion. The results clearly showcase the possibilities offered by using VCD spectroscopy in the characterization of chiral organocatalysts. [ABSTRACT FROM AUTHOR]

A cinchona alkaloid-functionalized heterogeneous catalyst is prepared through a thiol-ene click reaction of chiral N-(3,5-ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co-condensation of 1,2-bis(triethoxysilyl)ethane and 3-(triethoxysilyl)propane-1-thiol. Structural analyses and characterizations disclose its well-defined chiral single-site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β-trifluoromethyl-β,β-disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β-trifluoromethyl-β-hydroxy ketones through a sequential epoxidation-relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enone, showing an attractive feature in a practical construction of enriched chiral β-CF3-substituted molecules. [ABSTRACT FROM AUTHOR]

The first catalytic enantioselective conjugate alkynylation of α,β-unsaturated 1,1,1-trifluoromethyl ketones has been carried out. Terminal alkynes and 1,3-diynes were treated with trifluoromethyl ketones in the presence of a low catalytic load of a CuI-MeOBIPHEP complex (2.5 mol %) and triethylamine (10 mol %) to give the corresponding trifluoromethyl ketones bearing a propargylic stereogenic center at the β position with good yields and excellent enantiomeric excesses in most of the cases. No 1,2-addition products were formed under the reaction conditions. The procedure showed broad substrate scope for alkyne, diyne, and enone. A rationale for the observed stereochemistry has been provided. Finally, the potential application of the reaction products in the synthesis of chiral tetrahydrofurans bearing a trifluoromethylated quaternary stereocenter has been devised. [ABSTRACT FROM AUTHOR]

Mechanistic insight into the construction of quaternary silicon chiral centers by rhodium-catalyzed synthesis of spiro-9-silabifluorenes through dehydrogenative silylation is reported. The C2-symmetric bisphosphine ligand, BINAP, was effective in controlling enantioselectivity, and axially chiral spiro-9-silabifluorenes were obtained in excellent yields with high enantiomeric excess. Monitoring of the reaction revealed the presence of a monohydrosilane intermediate as a mixture of two constitutional isomers. The reaction proceeded through two consecutive dehydrogenative silylations, and the absolute configuration was determined in the first silylative cyclization. Competitive reactions with electron-rich and electron-deficient dihydrosilanes indicated that the rate of silylative cyclization increased with decreasing electron density on the silicon atom of the starting dihydrosilane. Further investigation disclosed a rare interconversion between the two constitutional isomers of the monohydrosilane intermediate with retention of the absolute configuration. [ABSTRACT FROM AUTHOR]

A silver-catalyzed 1,3-dipolar cycloaddition of fluorinated azomethine ylides and activated olefins is reported. The reaction offers a straightforward and atom-economical procedure for the preparation of fluorinated pyrrolidines. Broad scope and high levels of diastereoselectivity have been achieved simply by using AgOAc/PPh3 as the catalyst system. The high efficiency of the cycloaddition relies on the presence of a metal-coordinating group on the imine moiety, such as an ester or heteroaryl group. The asymmetric version of the cycloaddition has been developed by using Taniaphos as a chiral ligand. [ABSTRACT FROM AUTHOR]

A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product. [ABSTRACT FROM AUTHOR]

The enantioselective bromocyclization of allylic amides catalyzed by phosphorus-containing Lewis bases was examined in detail. A series of control experiments and NMR studies showed that a partially oxidized bis-phosphine generated in situ serves as the actual enantioselective catalyst. The reaction mechanism involves distinct roles of two Lewis basic sites, P and P=O, with P+Br serving as a fine-tuning element for substrate fixation in the chiral environment, and P+OBr as the Br+ transfer agent to the olefin. Catalyst loading could be reduced to as little as 1 mol %, and the reaction affords enantioenriched oxazolines with up to >99.5 % ee. [ABSTRACT FROM AUTHOR]

Chiral monodentate phosphines based on ortho-disubstituted ferrocene units have been prepared and used for the synthesis of gold(I) complexes. These complexes are highly active catalysts for the cycloisomerization of 3-hydroxy-1,5-enynes into bicyclo[3.1.0]hexanones. Their high catalytic activity is ascribed to their structural analogy to the biaryl-based Buchwald phosphines. This paper discloses the first enantioselective variant of these reactions based on gold catalysis ( ee's up to 80 %). [ABSTRACT FROM AUTHOR]

In this study, enantiopure imidazolidinones containing two hydroxyphenyl groups were synthesized, and the Williamson synthesis of the chiral bisphenols thus prepared with dihalides afforded polyethers containing chiral imidazolidinone repeating units. These chiral imidazolidinone polyethers exhibited excellent catalytic activity in the asymmetric Diels–Alder reaction. With the use of these polymeric catalysts, enantioselectivities up to 99% were obtained, higher than those obtained by the corresponding monomeric imidazolidinone catalyst in homogeneous solution. The polymeric catalysts were found to be insoluble in commonly used organic solvents, and they could be repeatedly used without the loss of activity. [ABSTRACT FROM AUTHOR]

Through systematic variation of the amine moiety, the protecting group, and the aryl substituents, α,α,α,α ‐ tetraaryl ‐ 1,3 ‐ dioxolane ‐ 4,5 ‐ dimethanol (TADDOL) ‐ based phosphoramidites have been optimized for the Ni ‐ catalyzed cycloisomerization of dienes. Diethyl diallylmalonate and other diallylic substrates including unsymmetrical dienes were converted to the corresponding exo ‐ methylenecyclopentanes with unprecedented activities of up to ≈13 500 h−1, very high selectivities, and enantioselectivities of up to 92 % ee. For more details see the Full Paper by C. Schmitz, W. Leitner, and G. Franciò on page 10696 ff. [ABSTRACT FROM AUTHOR]

Carboxylation Transition metal ‐ promoted carboxylation of various organic compounds has attracted much attention, and various types of reactions have been reported. In their Full Paper on page   1170   ff., which is featured on the Back Cover, Nozomi Saito, Zhongdong Sun, and Yoshihiro Sato report on the nickel(0) ‐ promoted carboxylation of aryl ynol ether that proceed in a highly regioselective manner to produce α ‐ substituted β ‐ aryloxyacrylic acid derivatives. Such derivatives could be transformed into the corresponding optically active β ‐ aryloxypropionic acid derivatives via rhodium ‐ catalyzed asymmetric hydrogenation. [ABSTRACT FROM AUTHOR]

The cover picture shows the asymmetric hydroboration of challenging 1,1‐disubstituted olefins by using phosphinooxazoline‐based phosphite‐oxazoline iridium ligands. In their Full Paper, M. Magre, M. Biosca et al. show that introducing the biaryl phosphite moiety in ligand design is highly adventitious in terms of substrate versatility. The 3 D structure of the phosphite‐based phosphinooxazoline ligand is a graphical representation rather than a known structure. The article highlighted by this cover can be found on p. 114 ff. of Issue 1, 2015. [ABSTRACT FROM AUTHOR]

An iridium‐catalyzed asymmetric allylic benzylation of aryl vinyl carbinols under light irradiation is described. 2‐Methylbenzophenone derivatives are employed and activated to hydroxy‐o‐quinodimethanes by an ultraviolet (UV) light. This approach enables asymmetric allylic benzylation with high enantioselectivity (up to 99 % ee) from readily available 2‐methylbenzophenones without the utilization of strong bases, and pre‐activation or pre‐functionalization of the substrates. Moreover, deuterium experiments reveal the generation of nucleophilic benzyl species from 2‐methylbenzophenone under UV irradiation. [ABSTRACT FROM AUTHOR]

Silaspiranes have attracted particular attention due to their chiral spiro‐silicon center, which serves as an ideal carbon isostere and can endow spiro‐analogs with distinct properties. Distinct from previously reported cyclization or cycloaddition strategies to form 5/5‐silaspiranes, we report herein the asymmetric dual ring expansion of spirosilabicyclobutanes with alkynes to synthesize axially chiral spirosilabicyclohexenes bearing a novel 6/6‐silaspirane framework. DFT (density functional theory) calculations provide the deep insight into the origin of the high enantioselectivity controlled by the sterically demanding binaphthyl phosphoramidite ligand. Preliminary studies of chiroptical properties indicate that one of the spirosilabicyclohexene analogs exhibit fluorescence emission, Cotton effects and CPL (circularly polarized luminescence) activity. [ABSTRACT FROM AUTHOR]

Rh‐catalyzed dynamic kinetic intramolecular [4+2] cycloaddition reaction of 1,3‐disubstituted allene‐1,3‐dienes afforded cis‐fused [4.3.0]bicyclic products with an excellent chemo‐, diastereo‐, and enantio‐selectivity. Many synthetically useful functional groups are tolerated. The synthetic utility has been demonstrated. Based on the careful experimental studies, a mechanism involving the rapid racemization of the allene moiety in the starting materials has been proposed. [ABSTRACT FROM AUTHOR]

We have studied the enantioselective transannular aminohalogenation reaction of unsaturated medium‐sized cyclic benzosulfonamides by using both chiral Brønsted acid and phase‐transfer catalysis. Under optimized conditions, a variety of bicyclic adducts can be obtained with good yields and high enantioselectivities. The mechanism of the reaction was also studied by using computational tools; we observed that the reaction involves the participation of a conformer of the nine‐membered cyclic substrate with planar chirality in which the stereochemical outcome is controlled by the relative reactivity of the two pseudorotational enantiomers when interacting with the chiral catalyst. [ABSTRACT FROM AUTHOR]