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Organic‐chemical literature encompasses large numbers of catalysts and reactions they can effect. Many of these examples are published merely to document the catalysts' scope but do not necessarily guarantee that a given catalyst is "optimal"—in terms of yield or enantiomeric excess—for a particular reaction. This paper describes a Machine Learning model that aims to improve such catalyst‐reaction assignments based on the carefully curated literature data. As we show here for the case of asymmetric magnesium catalysis, this model achieves relatively high accuracy and offers out of‐the‐box predictions successfully validated by experiment, e.g. in synthetically demanding asymmetric reductions or Michael additions. [ABSTRACT FROM AUTHOR]

Chiral phosphoric acid (CPA) has been established as a cornerstone in chemical synthesis reactions for over five decades, owing to its distinctive molecular structure and remarkable catalytic effect. However, in recent years, a revolutionary approach to asymmetric synthesis has emerged, utilizing photocatalytic excitation of molecules to generate free radicals, effectively surpassing the limitations of classical organic synthesis methodologies.A prominent and significant area of research has been dedicated to the investigation of chiral phosphoric acid synergistic photocatalysis for enantioselective chemical synthesis. This unique catalytic system encompasses a bifunctional hydrogen‐bonding catalyst, enabling simultaneous interactions between radical intermediates and substrates. The review paper focuses on the application and progress of this catalytic system in asymmetric synthesis throughout the past decade. [ABSTRACT FROM AUTHOR]

Predicting enantioselectivities in asymmetric catalytic reactions through chemometric approach is a challenging area. In this paper, quantitative structure−selectivity relationship (QSSR) models were successfully developed for thiol addition to N‐acylimines catalyzed by chiral phosphoric acids. Ten Dragon molecular descriptors calculated from thiols and phosphoric acid catalysts were used to correlate with 1075 enantioselectivities ΔΔG. Machine learning algorithms, support vector machine (SVM) and random forest (RF), were adopted to build QSSRs after descriptor subset selection based on the multiple linear regression technique. The SVM and RF models, respectively, have coefficient of determination R2 of 0.925 and 0.944 for the training set, and of 0.837 and 0.851 for the test set. Both SVM and RF models were subjected to internal and external validation and estimation in prediction ability and systematic error. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The 21st century has witnessed a continuous evolution in the development of boron‐stereogenic chemistry. Since the 1990s, various innovations for the synthesis of tetracoordinate boron‐stereogenic compounds, which exhibited great potential applications, have been demonstrated by synthetic chemists. This paper reviews the significant progress and recent advances towards the assembly of enantioenriched boron‐stereogenic compounds, and hopes to shed light on new perspectives and inspire further research in this emerging field. [ABSTRACT FROM AUTHOR]

Chiral Metal‐Organic Frameworks (CMOFs) is a kind of material with great application value in recent years. Formed by the coordination of metal ions or metal clusters with organic ligands. It has ordered and adjustable pores, multi‐dimensional network structure, large specific surface area and excellent adsorption properties. This material structure combines the properties of metal‐organic frameworks (MOFs) with the chiral properties of chiral molecules. It has great advantages in catalysis, adsorption, separation and other fields. Therefore, it has a wide range of applications in chemistry, biology, medicine and materials science. In this paper, various synthesis strategies and preparation methods of chiral metal‐organic frameworks are reviewed from different perspectives, and the advantages of each method are analyzed. In addition, the applications of chiral metal‐organic framework materials in enantiomer recognition and separation, circular polarization luminescence and asymmetric catalysis are systematically summarized, and the corresponding mechanisms are discussed. Finally, the challenges and prospects of the development of chiral metal‐organic frame materials are analyzed in detail. [ABSTRACT FROM AUTHOR]

In this paper, Pd‐catalyzed [4+2] decarboxylative cycloaddition of 4‐vinylbenzodioxinones with barbiturate‐derived alkenes has been developed, leading to various spirobarbiturate−chromane derivatives in high yields with excellent diastereo‐ and enantioselectivities. The scale‐up reaction and further derivation of the product were demonstrated. A plausible reaction mechanism was also proposed. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The asymmetric partial reduction of 1,3‐diketones stands as a straightforward pathway to access optically active β‐hydroxyketones. In this paper, an asymmetric Piers‐type hydrosilylation of 2,2‐difluoro‐1,3‐diketones was successfully realized by using a frustrated Lewis pair of chiral borane and tricyclohexylphosphine as a catalyst, delivering a variety of α,α‐difluoro‐β‐hydroxyketones in high yields with up to 99% ee. Significantly, no over‐reduced diol products were observed even with an excess amount of silanes. The product can be conveniently converted to α,α‐difluoro‐β‐hydroxyester or 1,3‐anti‐diol via an oxidation with m‐CPBA or a reduction with DIBAL‐H without obvious loss of ee. [ABSTRACT FROM AUTHOR]

Based upon their exceptional reactivity as cooperative Brønsted acid‐base catalysts chiral diphosphane Pd‐aqua complexes have successfully been utilized in a broad range of asymmetric transformations. Originally discovered by Sodeoka 25 years ago, they readily form reactive chiral Pd enolates upon deprotonation of β‐dicarbonyl compounds and simultaneously, a Brønsted acid liberated from the catalyst activates the electrophile. After the initial report and some ensuing papers had been published in the early 2000s, the field lay dormant for more than a decade. In recent years, however, new developments towards the enantioselective synthesis of various heterocycles and other useful compounds have evolved which take advantage of the unique properties of chiral Pd‐aqua complexes. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The asymmetric hydrogenation of N‐heteroarenes provides an efficient method for the synthesis of optically active cyclic secondary amines. In this paper, we described an asymmetric hydrogenation of phenanthridines using a chiral mono‐alkene‐derived borane. A variety of dihydrophenanthridines were furnished in high yields with up to 93% ee. The current catalytic system was very sensitive for the steric hindrance of phenanthridines. Bulky substituents at one phenyl group of phenanthridines were required to obtain the high enantioselectivity. But large substituents on the carbon of the C=N bonds would diminish the reactivity sharply. [ABSTRACT FROM AUTHOR]

This paper presents a Mn(I)‐catalysed methodology for the enantioselective hydrophosphination of terminal alkenyl aza‐heteroarenes. The catalyst operates through H−P bond activation, enabling successful hydrophosphination of a diverse range of alkenyl‐heteroarenes with high enantioselectivity. The presented protocol addresses the inherently low reactivity and the commonly encountered suboptimal enantioselectivities of these challenging substrates. As an important application we show that this method facilitates the synthesis of a non‐symmetric tridentate P,N,P‐containing ligand like structure in just two synthetic steps using a single catalytic system. [ABSTRACT FROM AUTHOR]

The tremendous importance of dirhodium paddlewheel complexes for asymmetric catalysis is largely the result of an empirical optimization of the chiral ligand sphere about the bimetallic core. It was only recently that a H(C)Rh triple resonance 103Rh NMR experiment provided the long‐awaited opportunity to examine – with previously inconceivable accuracy – how variation of the ligands impacts on the electronic structure of such catalysts. The recorded effects are dramatic: formal replacement of only one out of eight O‐atoms surrounding the metal centers in a dirhodium tetracarboxylate by an N‐atom results in a shielding of the corresponding Rh‐site of no less than 1000 ppm. The current paper provides the theoretical framework that allows this and related experimental observations made with a set of 19 representative rhodium complexes to be interpreted. In line with symmetry considerations, it is shown that the shielding tensor responds only to the donor ability of the equatorial ligands along the perpendicular principal axis. Axial ligands, in contrast, have no direct effect on shielding but may come into play via the electronic cis ${cis}$ ‐effect that they exert onto the neighboring equatorial sites. On top of these fundamental interactions, charge redistribution within the core as well as the electronic trans ${trans}$ ‐effect of ligands of different donor strengths is reflected in the recorded 103Rh NMR shifts. [ABSTRACT FROM AUTHOR]

Cyclopropane structure has been the object of interest in multiple investigations due to its prevalence in different natural products. In addition, this structure has a particular reactivity, specifically the 1,1‐cyclopropanedicarboxylate compounds, which act as acceptor‐donor cyclopropanes. Its reactivity could be compared with that of an α,β‐unsaturated carbonyl, which undergoes conjugate addition reaction and depending on the nature of the nucleophile this can lead to a cycloaddition reaction. Therefore, cyclopropane can be transformed into several useful structures in organic synthesis. Different methods have been described to achieve cyclopropanes such as, Simmons‐Smith reaction, decomposition of diazoalkanes and Michael‐Initiated ring closure (MIRC). Due to the absence of metals, this last method has been applied to the asymmetric organocatalytic synthesis of cyclopropanes, where the substrates activation is through the imine‐enamine intermediates formation or by hydrogen bonds. The asymmetric reaction consists of a domino reaction composed of a conjugate addition reaction and a cyclization reaction via intramolecular nucleophilic substitution. In this review, different asymmetric organocatalytic syntheses of the last two decades until 2021 are presented. With the intention to facilitate the reading of the review, an example of each paper was selected with the optimal reaction conditions and with the best organocatalyst producing the best yield and high stereoselectivity. [ABSTRACT FROM AUTHOR]

More information can be found in the Full Paper by H. Westphal, R. Warias et al. GLO:BDBK/15dec21:cctc202101739-toc-0001.jpg PHOTO (COLOR): . gl GLO:BDBK/15dec21:cctc202101739-toc-0001.jpg PHOTO (COLOR): . gl Footnotes 1 These authors contributed equally to this manuscript. Keywords: Analytical methods; Asymmetric catalysis; Heterogeneous catalysis; Lab-on-a-chip; Microreactors EN Analytical methods Asymmetric catalysis Heterogeneous catalysis Lab-on-a-chip Microreactors 5056 5056 1 12/22/21 20211215 NES 211215 B The Front Cover b illustrates a vortex that engulfs entire laboratory equipment and turns it into a single chip unit on the other side. In their Full Paper, H. Westphal, R. Warias et al. present a method to study immobilized organocatalysts and their performance in stereoselective transformations. [Extracted from the article]

This paper reports a new method for studying stereoselective catalyzed reactions at a small scale. For this purpose, a micro‐sized chemical reactor and a chiral chromatographic column were integrated on a single microfluidic chip hyphenated to mass spectrometry. By running the integrated reactor in truly continuous‐flow operation with an automated injection strategy, catalytic processes and their stereoselectivity can be observed over an extended range of time with significantly small consumption of samples, solvents, and catalytic material. [ABSTRACT FROM AUTHOR]

As an important branch of the Michael addition reaction, the aza‐Michael addition cascade reaction has been developed rapidly in recent years. This is because the reaction serves as an important method for effectively constructing functionalized C−N bonds, which can be widely used in the synthesis of chiral drugs and their intermediates and natural products. Given the importance of this topic, this review highlights the recent developments of aza‐Michael addition triggered cascade reactions in asymmetric synthesis, including aza‐Michael/Michael, aza‐Michael/Aldol, aza‐Michael/Henry, aza‐Michael/hemiacetal, aza‐Michael/Mannich, aza‐Michael/alkylation, aza‐Michael/cyclization, aza‐Michael/ring‐opening, aza‐Michael‐IED/HAD, aza‐Michael/INCR, and aza‐Michael/1,6‐conjugate addition reactions. In this paper, the reaction mechanism and derivatization experiments of different reactions are timely introduced to provide a more comprehensive theoretical basis for subsequent studies. [ABSTRACT FROM AUTHOR]

Supramolecular capsules can be used to change the activity and selectivity of a catalyst through the influence of the second coordination sphere, reminiscent of how enzymes control the selectivity of their processes. In enzymes, this approach is used to also control the enantioselectivity of reactions in which the active catalytic site is often not chiral but the second coordination sphere is. We are interested in the possibility to generate a chiral second coordination sphere around an otherwise achiral transition metal complex for asymmetric catalysis. In this paper we show that the ligand template approach can be used to generate a chiral second coordination sphere around a rhodium complex, which is used in asymmetric hydroformylation. [ABSTRACT FROM AUTHOR]

The contributions include transition-metal catalysis, organocatalysis, nanocatalysis, photoredox catalysis towards preparing carbocyclic and heterocyclic compounds of potential interest for life and material sciences. Carbocycles, heterocycles, organocatalysis, transition-metal catalysis, photoredox catalysis, nanocatalysis, asymmetric catalysis Keywords: carbocycles; heterocycles; organocatalysis; transition-metal catalysis; photoredox catalysis; nanocatalysis; asymmetric catalysis EN carbocycles heterocycles organocatalysis transition-metal catalysis photoredox catalysis nanocatalysis asymmetric catalysis 2962 2964 3 07/21/21 20210707 NES 210707 Ring synthesis via catalysis has emerged as a transformative platform. [Extracted from the article]

The cycloisomerization reaction of γ‐alkynoic acids mediated by transition‐metal catalysts has become a successful strategy for accessing enol lactones during the past few years. In their Full Paper on page 545, Cecilio Alvarez‐Toledano and co‐workers developed a fast and efficient protocol for the regio and diastereoselective cycloisomerization of β‐hydroxy‐γ‐alkynoic acids, catalyzed by the inexpensive and air‐stable catalyst CuBr (5 mol%) in water under microwave heating. This method provides rapid access to a variety of highly functionalized Z‐enol‐γ‐lactones in good yields under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Well‐defined supramolecular interactions are a powerful tool to control the stereochemistry of a catalytic reaction. In this paper, we report a novel core motif for fluxional 2,2′‐biphenyl ligands carrying (S)‐amino acid‐derived interaction sites in 5,5′‐position that cause spontaneous enrichment of the Rax rotamer. The process is based on strong non‐covalent interlocking between interaction sites, which causes diastereoselective formation of a supramolecular ligand dimer, in which the axial chirality of the two subunits is dictated by the stereochemical information in the amino acid residues. The detailed structure of the dimer was elucidated by NMR spectroscopy and single‐crystal X‐ray analysis. Three different phosphorus‐based ligand types, namely a bisphosphine, a bisphosphinite and a phosphoramidite were synthesized and characterized. Whereas the first one was found to exist in a strongly weighted equilibrium, the two others each exhibited stereoconvergent behavior transforming into the diastereopure Rax rotamer. Enriched ligands were used in rhodium‐mediated asymmetric hydrogenation reactions of prochiral olefins in which very high enantioselectivities of up to 96:4 were achieved. [ABSTRACT FROM AUTHOR]

Aziridines, the nitrogen counterparts of epoxides, are among the most challenging and intriguing heterocycles in organic chemistry, since they not only represent the endpoints of several total syntheses as common scaffolds in natural products, but also act as crucial precursors of complex molecules. The present review provides a brief overview of aziridine derivatives as well as the authors' choice of published papers that highlight recent enhancements concerning asymmetric organocatalytic strategies involved in aziridination reactions. Covalent or not? The present review provides a concise overview of current employments of asymmetric organocatalysis toward the enantioselective synthesis of aziridine derivatives. Specifically, after briefly introducing peculiar properties of aziridines, outstanding examples of covalent and non‐covalent activation methods are reported. [ABSTRACT FROM AUTHOR]

Keywords: Organocatalysis; Asymmetric catalysis; Tetrahydrothiophenes; Squaramides; Density functional calculations EN Organocatalysis Asymmetric catalysis Tetrahydrothiophenes Squaramides Density functional calculations 490 490 1 01/28/21 20210120 NES 210120 B The Cover Feature b shows that Cinchona hits the bull's-eye! In their Full Paper, Z. A. Mala et al. describe step-by-step how chiral Cinchona alkaloid squaramide plays a key role in the decomposition of dithiane diol to generate reactive mercaptoaldehyde. [Extracted from the article]

This study identifies new phosphite-oxazoline ligands that have been successfully applied in the palladium-catalyzed intermolecular asymmetric Heck reaction. The design of the new phosphite-oxazoline ligands derives from a previous successful generation of phosphine-oxazoline ligands, by replacing the phosphine group with several π-acceptor biaryl phosphite moieties. With these simple modifications, the new phosphite-based ligands, unlike previous phosphine-oxazoline, not only present a modular design with numerous potential phosphite groups available, but they are also air-stable solids, which can be made in the same number of synthetic steps as the phosphine analogues. The substitution of the phosphine by a biaryl phosphite group extended the range of substrates and triflates sources that can be coupled with regio-, enantioselectivities and activities comparable to the few best ones reported. In addition, the ligands that provided the best selectivities contained an isopropyl oxazoline moiety instead of the tert-butyl group found in the related phosphine-oxazoline ligands, which is made from a much more expensive precursor. In this paper we have also carried out kinetic studies and a Hammett plot analysis to determine the rate determining step of this system in the regime of interest. We suggest a likely explanation for the fast Heck reaction of the phosphite-oxazoline catalysts. [ABSTRACT FROM AUTHOR]

Anilines generally act as N-nucleophiles in transition-metal-catalyzed allylic substitution reactions. In this paper, a highly enantioselective intramolecular Friedel-Crafts-type allylic alkylation of aniline derivatives was realized by using an iridium catalyst derived from [Ir(cod)Cl]2 and ( Ra)-BHPphos. Various tetrahydroisoquinilin-5-amines were obtained in moderate to good yields, excellent enantioselectivity and regioselectivity under mild reaction conditions. BHPphos= N-benzhydryl- N-phenyldinaphthophosphoramidite. [ABSTRACT FROM AUTHOR]

Choosing the optimal catalyst for a new transformation is challenging because the ideal molecular requirements of the catalyst for one reaction do not always simply translate to another. Large groups at the 3,3′ positions of the binaphthol rings are important for efficient stereoinduction but if they are too large this can lead to unusual or poor results. By applying a quantitative steric assessment of the substituents at the 3,3′ positions of the binaphthol ring, we have systematically studied the effect of modulating this group on enantioselectivity for a wide range of reactions involving imines, and verified this analysis using ONIOM calculations. We have shown that in most reactions, the stereochemical outcome depends on both proximal and remote sterics. Summarising detailed calculations into a simple qualitative model identifies and explains the steric features required for high selectivity. This model is consistent with seventy seven papers reporting reactions (over 1000 transformations in total), and provides a straightforward decision tree for selecting the best catalyst. [ABSTRACT FROM AUTHOR]

A novel catalytic system for radical cross‐coupling reactions based on copper and chiral Pyridyl‐bis(imidazole) (PyBim) ligands is described. It overcomes the challenges of chemoselectivity and enantioselectivity, achieving a highly enantioselective vicinal sulfonyl‐esterification reaction of alkenes involving sulfur dioxide. This strategy involves the use of earth‐abundant metal catalyst, mild reaction conditions, a broad range of substrates (84 examples), high yields (up to 97% yield), and exceptional control over enantioselectivity. The reaction system is compatible with different types of radical precursors, including O‐acylhydroxylamines, cycloketone oxime esters, aryldiazonium salts, and drug molecules. Chiral ligand PyBim is identified as particularly effective in achieving the desired high enantioselectivity. Mechanistic studies reveal that copper/PyBim system plays a vital role in C─O coupling, employing an outer‐sphere model. In addition, the side arm effect of ligand is observed. [ABSTRACT FROM AUTHOR]

Microemulsions provide a unique opportunity to tailor the polarity and liquid confinement in asymmetric catalysis via nanoscale polar and nonpolar domains separated by a surfactant film. For chiral diene Rh complexes, the influence of counterion and surfactant film on the catalytic activity and enantioselectivity remained elusive. To explore this issue chiral norbornadiene Rh(X) complexes (X=OTf, OTs, OAc, PO2F2) were synthesized and characterized by X‐ray crystallography and theoretical calculations. These complexes were used in Rh‐catalyzed 1,2‐additions of phenylboroxine to N‐tosylimine in microemulsions stabilized either exclusively by n‐octyl‐β‐D‐glucopyranoside (C8G1) or a C8G1‐film doped with anionic or cationic surfactants (AOT, SDS and DTAB). The Rh(OAc) complex showed the largest dependence on the composition of the microemulsion, yielding up to 59 % (90 %ee) for the surfactant film doped with 5 wt% of AOT as compared to 52 % (58 %ee) for neat C8G1 at constant surfactant concentration. Larger domains, determined by SAXS analysis, enabled further increase in yield and selectivity while the reaction rate almost remained constant according to kinetic studies. [ABSTRACT FROM AUTHOR]

Repetitive Mizoroki‐Heck (MH) coupling polymerization was used to create novel chiral polyureas with cinchona alkaloids in the main chain. Apart from two‐component polycondensation of cinchona urea dimers with diiodobenzene via MH reaction conditions, some chiral polyureas were easily polymerized under self polycondensation to yield the chiral polymers. The asymmetric Michael addition reaction was successfully carried out using chiral polymers derived cinchona urea. Interestingly, phenolic‐based chiral polymers served as heterogeneous catalysts for the enantioselective Michael reaction, with high catalytic activity and excellent enantioselectivities (up to 99 % ee). These polymeric catalysts were also stable, and they could be recycled and reused. [ABSTRACT FROM AUTHOR]

Different densely substituted L‐ and D‐proline esters were prepared by asymmetric (3+2) cycloaddition reactions catalyzed by conveniently selected EhuPhos chiral ligands. The γ‐nitro‐2‐alkoxycarbonyl pyrrolidines thus obtained in either their endo or exo forms were functionalized and coupled to yield the corresponding γ‐dipeptides. The catalytic properties of these latter dimers were examined using aldol and conjugate additions as case studies. When aldol reactions were analyzed, an additive behavior in terms of stereocontrol was observed on going from the monomers to the dimers. In contrast, in the case of the conjugate additions between ketones and nitroalkenes, the monomers did not catalyze this reaction, whereas the different γ‐dipeptides promoted the formation of the corresponding Michael adducts. Therefore, in this latter case emergent catalytic properties were observed for these novel γ‐dipeptides based on unnatural proline derivatives. Under certain conditions stoichiometric amounts of ketone, acid and nitroalkene), formation of N‐acyloxy‐2‐oxooctahydro‐1H‐indoles was observed. [ABSTRACT FROM AUTHOR]

Diastereoselective double C−H heteroarylation of chiral ferrocenes provides valuable compounds with multiple functionalities using mild reaction conditions and simple reagents. Pd‐Complexes with chiral mono‐protected amino acids afforded corresponding heteroarylated ferrocenyl amines in good yields and high diastereomeric purities. In this way, a variety of indole, thiophene, pyrrole, or furan substituents were introduced to the ferrocene moiety. Furthermore, a range of relevant functional groups, for example ketone, ester, chloro, nitro, or silyl, are tolerated by this method. An alternative combination of amino acid and ferrocenyl amine configurations was leveraged to provide the complementary diastereomeric products. The products of C−H heteroarylation can be transformed into corresponding phosphines. Absolute configurations of CH‐activation products were confirmed by the combination of X‐ray crystallographic analysis and CD spectroscopy. 19F NMR kinetic study and DFT calculations provided insights into the reaction mechanism and reasons governing stereoinduction. [ABSTRACT FROM AUTHOR]

Disubstituted oxindoles represent an important family of bioactive compounds and synthetic derivatives that mimic natural products. The construction of the asymmetric quaternary carbon at C-3 or C-2 is therefore a challenging problem for organic chemists. In the last years, many papers have appeared on asymmetric catalytic methods for the synthesis of these compounds, in particular about spirocyclic derivatives and this literature has been largely reviewed, as well as the literature on 3-substituted-3-hydroxyoxindoles and 3-substituted-3-aminooxindoles. On the other hand, the literature on non-spirocyclic 3,3-dialkyloxindoles as well as on 2,2-disubstituted 3-indolinones has not fully reviewed since our previous review on this topic. This review aims to fill this gap covering the literature on these topics. Abbreviations: Alloc=allyloxycarbonyl; Ant=anthracenyl; BINOL=1,1′-binaphthalene-2,2′-diol; Boc= t-butoxycarbonyl; Bz=benzoyl; Cbz=benzyloxycarbonyl; CSA=camphorsulfonic acid; Cy=cyclohexyl; DABCO=1,4-diazabicyclo[2.2.2]octane; dba=bis(dibenzylideneacetone); DBU=1,8-diazabicyclo[5.4.0]undec-7-ene; DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone; (DHQD)2AQN=hydroquinidine (anthraquinone-1,4-diyl) diether; (DHQD)2PHAL=hydroquinidine 1,4-phthalazinediyl diether; (DHQD)2PYR=hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether; DIPEA= N, N-diisopropylethylamine; esp=α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid; HFIP=1,1,1,3,3,3-hexafluoro-2-propanol; HMDS=hexamethyldisilazane; β-ICD=β-isocupreidine; LG=leaving group; Mes=2,4,6-trimethylphenyl; Moc=methoxycarbonyl; MOM=methoxymethyl; MS=molecular sieves; MsOH=methanesulfonic acid; NHC=N-heterocyclic carbene; Npt=naphthyl; PG=protecting group; Phg=phenylglycine; Phth=phthalimidyl; Piv=2,2-dimethylpropanoyl; PMB=4-methoxybenzyl; Red-Al=sodium bis(2-methoxyethoxy)aluminium hydride; Suc=succinimidyl; TBDPS= tert-butyldiphenylsilyl; TBS= tert-butyldimethylsilyl; TES=triethylsilyl; TIPS=triisopropylsilyl; TMEDA= N, N, N′,N′-tetramethylethylenediamine; TMG=1,1,3,3-tetramethylguanidine; TMS=trimethylsilyl; Ts=4-toluenesulfonyl. [ABSTRACT FROM AUTHOR]

The catalytic, enantioselective oxidative cyclization of naphthol-derived carboxylic acids mediated by chiral hypervalent iodine reagents has been studied extensively in the recent past, but analogous reactions of non-carboxylic substrates are yet unknown. This paper describes a catalytic, enantioselective, hypervalent iodine-promoted oxidative cycloetherification reaction of naphtholic alcohols. The new process relies on a variant of the Uyanik-Ishihara catalyst, in which the stereogenic centers have been relocated closer to the iodine atom. The new catalyst design affords optical yields comparable to those available with Uyanik-Ishihara iodides, but chemical yields are sensibly higher, at least with the tests substrates. An even more problematic reaction is the catalytic, enantioselective oxidative cyclization of naphtholic sulfonamides. In this case, the new catalyst affords significantly higher optical inductions than Uyanik-Ishihara iodides. The kinetic resolution of particular naphtholic alcohols is demonstrated. The absolute configuration of a numver of enantioenriched compounds obtained in this study was ascertained by X-ray diffractometry. [ABSTRACT FROM AUTHOR]

For several decades of intensive research it has been accepted that the physical sizes and shapes of substituents are the main stereoregulating factors in Rh-catalyzed asymmetric hydrogenation. In this paper, it is argued on the basis of accumulated experimental and computational evidence that weak noncovalent attractive interactions between the substituents of the chiral ligand and the substrate strongly contribute to the process of stereoselection in Rh-catalyzed asymmetric hydrogenation in the same fashion as that observed in organocatalytic reactions and in biological enzymatic processes. [ABSTRACT FROM AUTHOR]

A new class of chiral C2‐symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd‐catalyzed asymmetric N‐allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional SN2‐coupling of a tartrate‐derived ditosylate with 6‐alkyl‐2‐bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd‐catalyzed N‐allylation of tert‐butyl glycinate with racemic (E)‐2,8‐dimethylnona‐5‐en‐4‐yl methyl carbonate (up to 95 % ee). In addition, the analogous transformation of tert‐butyl glycinate with methyl (E)‐nona‐5‐en‐4‐yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline‐derived dipeptide analogs ProM‐17 and ProM‐21. [ABSTRACT FROM AUTHOR]

PHANE-TetraPHOS, a new D2 symmetric tetraphosphane based on the [2.2]paracyclophane scaffold, has been synthesized and characterized. The peculiarity of this system is the presence of four homotopic diphenylphosphane groups, exchangeable through C2 symmetry operations and consequently indistinguishable. Their spatial arrangement allows the simultaneous complexation of two metal atoms. Enantiomeric purity was attained at tetra-phosphane oxide level by fractional crystallization of the diastereomeric adducts obtained from the racemate with enantiopure dibenzoyltartaric acids. Alkaline treatment of diastereomerically pure adducts followed by exhaustive P-O groups reduction with HSiCl3 gave both PHANE-TetraPHOS antipodes in an enantiopure state. They were tested as rhodium ligands in the homogeneous enantioselective hydrogenation of some benchmark unsaturated compounds. Catalytic activity and enantiodiscrimination ability were found comparable to those exhibited by the complexes of the parent bidentate ligand PHANEPHOS, but only half a mole of precious chiral ligand was employed. [ABSTRACT FROM AUTHOR]

This study reports the development and application of a conformer-dependent quantitative quadrant descriptor for generating models that relate catalyst performance to catalyst structure in enantioselective transformations. The generality of these descriptors is demonstrated by using them for three different reactions: (1) copper-catalyzed, enantioselective cyclopropanation of alkenes, (2) rhodium-catalyzed enantioselective hydrogenation of α-substituted N-acyl-enamides, and (3) enantioselective addition of thiols to N-acyl imines. This work will provide researchers an interpretable steric descriptor that merges the heuristic value of quadrant models with a quantitative tool that can be used to create statistically meaningful correlations between the steric occupancy of catalyst quadrants and stereoselectivity. The low dimensionality of this descriptor, its ability to capture conformational effects and stereostructure, and its direct relationship to intuitive structural properties make it particularly well-suited for creating Quantitative Structure-Selectivity Relationships (QSSR) with smaller datasets of asymmetric reactions. [ABSTRACT FROM AUTHOR]

This paper describes the preparation of enantioselective catalysts based on derivatives of imidazolidine-4-thione and their subsequent anchoring by means of a sulfur atom on a polymeric carrier. First, we verified the catalytic activity and enantioselectivity in the Henry reaction of the homogeneous variants of the catalysts, i.e., the copper(II) complexes of 2-(pyridine-2-yl)imidazolidine-4-thiones and 4-benzylsufanyl-2-(pyridine-2-yl)imidazolines themselves. It was found that these catalysts exhibit high enantioselectivity (up to 98% ee). Subsequently, the imidazolidine-4-thione catalysts were immobilized by anchoring to polymeric carriers based on a copolymer of styrene and 4-vinylbenzyl chloride. These heterogeneous catalysts were analogously tested with regard to their catalytic activity and enantioselectivity in the Henry reaction, and moreover, the possibility of their separation and reuse was studied. It was found that all the prepared immobilized catalysts are highly enantioselective (up to 97% ee). Their recycling ability was tested in Henry reaction of 2-methoxybenzaldehyde with nitromethane. It was found that they can be recycled more than ten times without any decrease of their enantioselectivity. Therefore, they present a better means of catalysis than the original copper(II) complexes of imidazolidine-4-ones from both economic as well as ecological points of view. Thus, such immobilized catalysts exhibit high application potential for the asymmetric Henry reaction. [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]

The Ir‐catalyzed conversion of prochiral tert‐cyclobutanols to β‐methyl‐substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β‐oxy‐substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM‐SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related RhI‐catalyzed transformations. Supported by DFT calculations we propose the initial formation of an IrIII hydride intermediate, which then undergoes a β‐C elimination (C−C bond activation) prior to reductive C−H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir‐catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo‐controlled synthesis of substituted chromanes related to the tocopherols and other natural products. [ABSTRACT FROM AUTHOR]

Efficient synthesis of optically active N‐fused 1,3‐oxazolidines containing quaternary and tertiary stereocenters was achieved via Pd‐catalyzed asymmetric (3+2) cycloadditions of sulfamate‐derived cyclic imines and vinylethylene carbonates. Using a chiral phosphoramidite ligand, the cycloadditions proceeded effectively providing sulfamidate‐fused 1,3‐oxazolidines in high yields (up to 96%) with stereoselectivities (up to 25:1 dr; >99% ee). Additionally, the scale‐up reaction and further transformations of the product were also achieved demonstrating the synthetic utility toward the construction of useful heterocycles such as chiral oxazoline bearing a quaternary stereocenter. [ABSTRACT FROM AUTHOR]

Under CuBr·SMe2/PPh3 catalysis (5/10 mol‐%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (–78 °C) undergo 1,4‐addition to Cbz or Boc protected quinolin‐4(1H)‐ones to provide 2‐alkyl‐2,3‐dihydroquinolin‐4(1H)‐ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc‐protected ethyl 6‐substituted 4(1H)‐quinolone‐3‐carboxylates (6‐R group = all halogens, n/i/t‐alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and ≈ 75 % ee on addition to the parent (6‐R = H). Ligand (S)‐(BINOL)P–N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)‐quinolone‐3‐carboxylate. Allylation and deprotection of a representative 1,4‐addition product example confirm the facial selectivity (X‐ray crystallography). [ABSTRACT FROM AUTHOR]

Guanosine‐rich DNA sequences can fold into quadruplex structures which are not only biologically relevant, but also promising for applications in aqueous homogenous catalysis. Here, an asymmetric Michael addition is catalyzed by covalently modified G‐quadruplexes in combination with copper ions. Using systematic chemical variation and various spectrometric techniques, the key parameters that govern rate acceleration and stereoselectivity were identified. More information can be found in the Full Paper by A. Jäschke et al. on page 12162 ff. [ABSTRACT FROM AUTHOR]

The chiral benzofuranone structural motif is a prominent feature in many natural products, which exhibit a broad range of biological and pharmaceutical activities. In the past few years, a survey of chiral benzofuranone derivatives based on asymmetric catalysis reveals an increasing number of papers, which reflects the latest achievements to facilitate the synthesis of sufficient quantities of related compounds as potential medicinal agents and biological probes. Recent advances in this area are summarized and classified according to the structure of the starting substrate. [ABSTRACT FROM AUTHOR]

This paper discloses the first uses of phosphahelicenes as chiral ligands in transition-metal catalysis. Unlike all known helical phosphines used so far in catalysis, the phosphorus function of phosphahelicenes is embedded in the helical structure itself. This crucial structural feature originates unprecedented catalytic behaviors and efficiency. An appropriate design and fine tuning allowed both high catalytic activity and good enantiomeric excesses to be attained in the gold promoted cycloisomerizations of N-tethered 1,6-enynes and dien-ynes. [ABSTRACT FROM AUTHOR]

This paper reviews the present state of the catalytic enantioselective Reformatsky reaction. Advancements in asymmetric versions of this reaction have recently led to a considerable extension of its scope and applicability, principally due to the use of highly active chiral ligands and very specific reaction conditions. [ABSTRACT FROM AUTHOR]

This paper describes the synthesis and characterization of 5-(diphenylphosphanyl)isophthalic acid bioconjugates (Lig-[R]2). In addition to symmetrically disubstituted conjugates with amino acids, peptides or amines, a convenient one-pot, two-step procedure for the synthesis of conjugates bearing two different substituents is reported. The 28 prepared phosphanes were used as monodentate ligands in the rhodium(I)-catalyzed hydrogenation of 2-acetamidoacrylate and ( Z)-α-acetamidocinnamate. The ligand with the smallest side-chain substituents Lig-[Ala-OMe]2 ( 1a) revealed the highest selectivity, with up to 84 % ee. The catalysts presented herein are models of artificial metalloenzymes in which the outer-coordination sphere controls the selectivity in catalysis. The chirality of distant hydrogen-bonded amino acids is transmitted by 'backdoor induction' to the prochiral RhI center. [ABSTRACT FROM AUTHOR]

The Mukaiyama aldol reaction of a silyl enol ether with an aldehyde mediated by TiCl4 was first published in 1973. After that, tremendous efforts have been made to improve this potentially versatile protocol, leading to remarkable advances of this reaction. In their Full Paper on page 3051 ff., Shū Kobayashi et   al. report on asymmetric Mukaiyama aldol reactions of silicon enolates with aldehydes catalyzed by chiral FeII and BiIII complexes. The reactions proceeded in the presence of water at 0 °C to afford the desired aldol products in high yields with high diastereo ‐ and enantioselectivities. The assumed catalytic cycle and transition states indicated important roles of water in these efficient asymmetric Mukaiyama aldol reactions. [ABSTRACT FROM AUTHOR]

Titanium-salan complexes with 3,3'-diphenyl substituents in the salicylidene rings of the salan ligand are efficient sulfoxidation catalysts, capable of catalyzing the asymmetric oxidation of bulky aryl benzyl sulfides with H2O2 with good to high enantioselectivities. In this paper, substituent effects on titanium-salan-catalyzed enantioselective oxidation of sulfides to sulfoxides have been systematically investigated. Titanium-salan catalysts with halogen substituents at the 5,5'-positions (3,3'-H2dihydrogen substituted) have been found to catalyze the oxidation of both bulky aryl benzyl sulfides and small alkyl phenyl sulfides with good to high enantioselectivities. Kinetic data witness a direct attack of the sulfide to the electrophilic active oxygen species; a consistent reaction mechanism is proposed. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Optically active hydrobenzoins are very important building blocks for further derivation of biologically active complexes, natural products, and pharmaceutical compounds. In this paper, A practical approach has been developed for asymmetric hydrogenation of benzils with Ru(OTf)(TsDPEN)(η6-cymene) as a pre-catalyst in methanol. Therefore, a series of chiral hydrobenzoins was synthesized in good yields with good to moderate diastereoselectivities and good to excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

In this paper we describe new asymmetric, catalytic strategies for the synthesis of biologically important α-methylene-δ-lactones and δ-lactams. The elaborated protocols utilize iminium-ion-mediated Michael addition of trimethyl phosphonoacetate to α,β-unsaturated aldehydes catalyzed by ( S)-(−)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether as the key step. Enantiomerically enriched Michael adducts are employed in three different reaction pathways. Transformation into α-methylene-δ-lactones is realized by a sequence of reactions involving chemoselective reduction of the aldehyde, followed by a trifluoroacetic acid (TFA)-mediated cyclization and Horner-Wadsworth-Emmons olefination of formaldehyde. On the other hand, indolo[2, 3- a]quinolizine-framework-containing products can be accessed when enantiomerically enriched Michael adducts are employed in a Pictet-Spengler reaction with tryptamine, followed by Horner-Wadsworth-Emmons olefination. Finally, reductive amination of the Michael adducts by using methylamine and Horner-Wadsworth-Emmons olefination of formaldehyde is demonstrated to give α-methylene-δ-lactams. The developed strategies can be realized without the purification of intermediates, thus greatly increasing their practicality. [ABSTRACT FROM AUTHOR]