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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 rare, perfect case of a highly selective regiodivergent reaction of a racemic mixture is presented. Upon interaction with the Pd – (S,S) ‐ NHC catalyst (NHC=N ‐ heterocyclic carbene), the R enantiomer takes the right fork and the S enantiomer the left one. Thus, the racemic mixture reacts to give two regioisomeric enantiopure products. In this reaction a methyl CH activation competes with an asymmetric CH ‐ bond activation in a methylene unit to give single enantiomers of substituted indolines. DFT was the tool to map out the course of the reaction and to extend and rationalize the outcome. For more details see the Full Paper by E. P. Kündig et al. on page 15021 ff. [ABSTRACT FROM AUTHOR]

A convergent and regioselective synthesis of silicon-bridged 4-arylpyridines has been developed through a rhodium-catalyzed [2+2+2] cycloaddition of silicon-containing diynes with nitriles. The absorption and emission properties of these compounds have been examined and could be tuned by varying the substituent on the benzene ring, as well as through the protonation or alkylation of the nitrogen atom on the pyridine ring. A catalytic asymmetric synthesis of silicon-centered axially chiral spirocyclic derivatives has also been achieved with high enantioselectivity by using a newly modified MeO-MOP (MeO-MOP=2-(diphenylphosphino)-2′-methoxy-1,1′-binaphthyl) derivative as the chiral ligand. These spirocyclic compounds were found to be CPL-active (CPL=circularly polarized luminescence), representing the first CPL-active compounds based on the chirality at silicon. [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]

The first chiral helicene‐NHC gold(I) complexes efficient in enantioselective catalysis were prepared. The L‐shaped chiral ligand is composed of an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold laterally substituted by a configurationally stable [5]‐helicenoid unit. The chiral information was introduced in a key post‐functionalization step of a NHC‐gold(I) complex bearing a symmetrical anionic fluoreno[5]helicene substituent, leading to a racemic mixture of complexes featuring three correlated elements of chirality, namely central, axial and helical chirality. After HPLC enantiomeric resolution, X‐ray crystallography and theoretical calculations enabled structural and stereochemical characterization of these configurationally stable NHC‐gold(I) complexes. The high potential in asymmetric catalysis is demonstrated in the benchmark cycloisomerization of N‐tethered 1,6‐enynes with up to 95 : 5 er. [ABSTRACT FROM AUTHOR]

A chiral N,N′‐dioxide‐nickel(II) complex‐catalyzed asymmetric amination of 3‐bromo‐3‐substituted oxindoles with anilines has been developed. A series of alkyl or aryl 3‐amino‐indolinones with quaternary stereocenters were obtained in high yields with excellent ee values in one step (up to 99 % yield, up to 96 % ee). The method provided a ready route to optically active intermediates of 3‐amino‐2‐oxindole‐based bioactive compounds. Moreover, a possible transition‐state model is proposed so as to elucidate the origin of the chirality based on the X‐ray crystal structure of the catalyst and the adduct. [ABSTRACT FROM AUTHOR]

A new method for the enantioselective synthesis of 5,5-disubstituted (quaternary) hydantoins was developed on the basis of an organocatalytic Michael reaction approach involving the use of 2-benzylthio-3,5-dihydroimidazol-4-ones as key hydantoin surrogates. The method is general with respect to the substitution pattern at the hydantoin N1 (alkyl, aryl, acyl), N3 (aryl), and C5 (linear/branched alkyl, aryl) positions and affords essentially single diastereomeric products with enantioselectivities higher than 95%ee in most cases. Among the bifunctional Brønsted base/H-bond catalysts examined, a known squaramide–tertiary amine catalyst and a newly prepared squaramide–tertiary amine catalyst provide the highest selectivity so far with either nitroolefins or vinyl ketones as the acceptor components. Kinetic measurements support a first-order rate dependence on both reaction partners, the donor template and the Michael acceptor, whereas competitive 1H NMR spectroscopy experiments reveal the high ability of the template for catalyst binding. [ABSTRACT FROM AUTHOR]

The concept of matched and mismatched stereochemical pairings has been utilised extensively in organic synthesis, with the cooperativity resulting from the former enabling many reactions to proceed with high stereoselectivity. This approach was first developed to improve the diastereoselectivity of a reaction by matching the configuration of an enantiopure reagent or catalyst with the configuration of an enantiopure substrate. It has been extended to the asymmetric transformation of prochiral substrates controlled by reagents and catalysts containing two or more stereogenic centres. Matched and mismatched pairings may again be identified, with the former resulting in higher product enantioselectivity. This Minireview examines stereochemical pairings within catalysts generated from the combination of a metal with an enantiopure ligand; specifically examples in which the ligand diastereoisomers examined for cooperativity are formally the result of the addition of a chiral element to an existing enantiopure ligand. Comparison of all three ligands in each of the fifty-six examples examined reveals that, in the majority of cases, the added element of chirality increases and decreases the enantioselectivity with respect to the parent ligand. The iterative application of this effect offers a potentially powerful method for catalyst optimisation for use in asymmetric synthesis. [ABSTRACT FROM AUTHOR]

An axial chiral version of the 2,6-dimesitylphenyl group attached to sulfur is reported. Its multistep preparation starts from ( S)-binol, and the thiol group is established by a racemization-free thermal Newman-Kwart rearrangement. The new chiral thiolate ligand decorated with one mesityl group is used in the synthesis of a tethered ruthenium chloride complex. Its spectroscopic characterization revealed solvent-dependent epimerization at the ruthenium center. The major diastereomer is crystallographically characterized. Chloride abstraction with tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF4) yields the corresponding coordinatively unsaturated ruthenium complex with the Ru−S bond exposed. Si−H bond activation at this Ru−S bond proceeds in syn fashion but with moderate facial selectivity (d.r.=70:30), generating diastereomeric chiral-at-ruthenium hydrosilane adducts. Their application to catalytic imine hydrosilylation led to promising enantioinduction (40 % ee), thereby providing proof of concept for asymmetric catalysis involving cooperative Si−H bond activation. [ABSTRACT FROM AUTHOR]

An unprecedented copper(I)-catalyzed asymmetric desymmetrization of 5-silylcyclopentadienes with in situ formed azoalkene was realized through an inverse-electron-demand aza-Diels-Alder reaction (IEDDA) pathway, in which 5-silylcyclopentadienes served as efficient enophiles. This new protocol provides a facile access to the biologically important heterocyclic tetrahydropyridazines containing a unique α-chiral silane motif and three adjoining stereogenic centers in generally good yield (up to 92 %) with exclusive regioselectivity, high diastereoselectivity (>20:1 diastereomeric ratio), and excellent enantioselectivity (up to 98 % enantiomeric excess). DFT calculations and control experiments further confirmed the proposed reaction mechanism. [ABSTRACT FROM AUTHOR]

A new type of axially chiral cyclo-[1,1′-biphenyl]-2,2′-diol (CYCNOL) ligands with adjustable dihedral angles have been developed by varying the bridge chain length. Eight-, nine- and ten-membered cyclo-ligands were prepared and evaluated by using two representative examples: enantioselective additions of diethylzinc to aldehydes and organometallic reagents to enones. The results revealed that the fine regulation of dihedral angles through variation of the bridge chain length was effective in the asymmetric synthesis. [ABSTRACT FROM AUTHOR]

A highly regio-, diastereo- and enantioselective Michael addition-alkylation reaction between α-substituted cyano ketones and ( Z)-bromonitrostyrenes has been realized by using a chiral N, N′-dioxide as organocatalyst. A variety of substrates performed well in this reaction, and the corresponding multifunctionalized chiral 2,3-dihydrofurans were obtained in up to 95 % yield with 95:5 dr and 93 % ee. [ABSTRACT FROM AUTHOR]

A catalytic asymmetric [3+2] cycloaddition reaction of chiral palladium-containing N1-1,3-dipoles with methyleneindolinones has been successfully developed. The reaction allows an efficient construction of 3,3′-pyrrolinyl spirooxindoles with high yields and excellent stereoselectivities (up to 93 % yield, 19:1 d.r. and >99 % ee). A synthetic application of this methodology is demonstrated and a stereocontrol mechanism is proposed. [ABSTRACT FROM AUTHOR]

The highly enantioselective preparation of pharmacologically interesting hexahydropyridazine derivatives based on a multicomponent cascade reaction is described. This one-pot approach utilizes an organocatalytic Michael reaction followed by intermolecular α-amination and intramolecular hemiaminalization to yield a chiral pyridazine backbone with contiguous stereogenic centers and multiple functional groups in good yield and with high stereoselectivity. Compounds synthesized by this method potently inhibited proliferation of MCF-7 breast cancer cells. Mechanistic studies suggest that compound 5 c exerts these 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]

The first asymmetric phospha-Michael addition of diarylphosphines to N-enoyl phthalimides has been developed in the presence of a chiral palladacycle catalyst. A library of free chiral tertiary phosphine adducts were directly obtained with excellent yields and enantioselectivities. Products can be subsequently functionalized to afford β-phosphinoamides, the direct preparation of which from cinnamides has been notoriously challenging. [ABSTRACT FROM AUTHOR]

An improved synthesis of a novel class of bidentate (P,N) ligands is presented, the structures of which are characterized by three distinct elements of chirality. The stereoselective installation of the elements of central chirality (at the benzylic carbon and the phosphorus atom) depends on the size of the phosphorus substituent. Thermal inversion of the phosphorus center has been studied experimentally and further correlated by DFT calculations. The potential of these ligands and the role of the phosphorus atom in the asymmetric α-arylation of aldehydes (Pd) and hydrogenation of allylic alcohols (Ir) have also been investigated. [ABSTRACT FROM AUTHOR]

A series of dichlorocyclophosphazanes [{ClP(μ-NR)}2] containing chiral and achiral R groups was obtained from simple commercially available amines and PCl3. Their condensation reactions with axially chiral biaryl diols yielded ansa-bridged chiral cyclophosphazane (CycloP) ligands. This highly modular methodology allows extensive elaboration of the ligand set, in which the chirality can be introduced at the diol bridge and/or the amido R group. This provides the possibility to observe match and mismatch effects in catalysis. A series of twenty CycloP ligands was synthesized and characterized by multinuclear NMR spectroscopy, HRMS, elemental analysis, and in selected cases, single-crystal X-ray diffraction. These studies show that all of the ditopic CycloP ligands are C2 symmetric, rendering their metal coordination sites symmetry equivalent. Two well-established enantioselective reactions were explored by using late-transition metal CycloP complexes as catalysts; the gold-catalyzed hydroamination of γ-allenyl sulfonamides and the asymmetric nickel-catalyzed three-component coupling of a diene and an aldehyde. The steric demands of the CycloP ligands have a subtle influence on the reactivity and selectivity observed in both reactions. Good enantiomeric ratios (e.r.) as high as 89:11 in the gold-catalyzed reaction and 92:8 in the nickel-catalyzed bis-homoallylation reaction were observed. [ABSTRACT FROM AUTHOR]

Carbon–carbon bond formation: A highly efficient method for the oxo‐hetero‐Diels–Alder reaction of 2‐oxoindolin‐3‐ylidenes based on chiral calcium phosphate is described. In general, adducts were obtained with high yields and excellent diastereo‐ and enantioselectivities (up to 96 % yield, >99:1 endo/exo, >99 % ee; see scheme, Boc=tert‐butoxycarbonyl). [ABSTRACT FROM AUTHOR]

α,β-Unsaturated esters have been employed as substrates in iridium-catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99 % ee) were obtained for a broad range of substrates with both aromatic- and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals. [ABSTRACT FROM AUTHOR]