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With chiral amine (DHQD)2PHAL as nucleophilic catalyst, asymmetric synthesis of enantioenriched 3‐allylindoles was achieved from indolone‐2‐imines and MBH carbonates. Compared with our previous chiral phosphine catalysis, the chiral amine had exactly the opposite effect in terms of enantioselectivity. Importantly, we could obtain each enantiomer by adjusting the catalyst system. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Allenoate zwitterion generated by nucleophilic catalysis annulates arylidenepyrazolone. • Methodology offers a facile entry to biologically important tetrahydropyranopyrazole. • The reaction proceeds with enantio- and diastereoselectivity in presence of quinidine. • The primary adduct undergoes further transformations with the initial chirality intact. Abstract The enantioselective synthesis of the tetrahydropyranopyrazole scaffold has been achieved. The quinidine catalyzed reaction of allenoates with arylidenepyrazolones proceeded with high enantio- and diastereoselectivity while the reactions of alkylidenepyrazolones were less efficient. Allene ketones also afforded tetrahydropyranopyrazole derivatives in high yields, however, with only moderate enantioselectivity. The primary adduct undergoes further functional group transformations without effecting the initially formed chiral centre. [ABSTRACT FROM AUTHOR]

A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions. A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). [ABSTRACT FROM AUTHOR]

A metal‐free, phosphine‐catalyzed intramolecular "umpolung Michael addition" on alkynes to form spiroindol(en)ines is reported. This nucleophilic catalysis enables the formation of a wide scope of five‐ and six‐membered spiroindol(en)ines in moderate to excellent yields in batch as well as under continuous‐flow conditions. Triphenylphosphine‐catalyzed nucleophilic activation of alkynes allows the exclusive formation of exo‐product under mild reaction conditions. A metal‐free, phosphine‐catalyzed intramolecular "umpolung Michael addition" on alkynes to form spiroindol(en)ines is reported. This nucleophilic catalysis enables the formation of a wide scope of five‐ and six‐membered spiroindol(en)ines in moderate to excellent yields in batch as well as under continuous‐flow conditions. [ABSTRACT FROM AUTHOR]

Chiral‐at‐metal bis‐cyclometalated iridium(III) complexes are introduced as a new class of chiral catalysts for the reaction of epoxides with CO2 to form cyclic carbonates under conditions of kinetic resolution. Reactions are typically performed at room temperature in the presence of 1 mol % of iridium catalyst and 1.5 mol % of tetraethylammonium bromide as the nucleophilic cocatalyst to provide selectivity factors of up to 16.6. A variety of monosubstituted epoxides, including styrene epoxide, epoxides with aliphatic side chains, glycidyl ethers, and a glycidyl ester, are found to be suitable substrates. No polymerization side reaction is observed for any of the investigated substrates. Chiral resolution: A bis‐cyclometalated chiral‐at‐iridium complex catalyzes the kinetic resolution of monosubstituted epoxides with carbon dioxide to provide non‐racemic cyclic carbonates at room temperature with selectivity factors up to 16.6. [ABSTRACT FROM AUTHOR]

This short review provides an overview of 7-azaindoline auxiliaries in asymmetric catalysis. 7-Azaindoline serves as a useful attachment to carboxylic acids, and the thus-formed 7-azaindoline amides are amenable to atom-economical C–C bond-forming reactions with high stereoselectivity. The attachment is used for the sake of gaining traction in promoting the reaction of interest and can be easily removed after enantioselective reactions. Both nucleophilic and electrophilic catalyses are realized with broad tolerance for functional groups, showcasing the usefulness of 7-azaindoline auxiliaries for practical and streamlined synthesis of a wide range of acyclic chiral building blocks. [ABSTRACT FROM AUTHOR]

We recently developed a novel chiral catalyst‐directed dynamic kinetic diastereoselective acylation of hemiacetals for the synthesis of carbohydrates. In this update, we describe a catalytic method for the dynamic kinetic enantioselective acylation of 2‐chromanols using benzotetramisole derived catalysts. High yields and enantiomeric excesses were obtained for a broad range of acylated 2‐chromanols, which are important intermediates for the synthesis of various bioactive pharmaceuticals. We hypothesize that the high stereoselectivity of the reaction originates from a novel cation‐n interaction between the chromanol substrate and the acylated catalyst. [ABSTRACT FROM AUTHOR]

A combination of an amino acid-derived chiral phosphine catalyst and methyl acrylate to catalyze the direct Mannich reaction of 3-substituted oxindoles and imines has been reported to afford 3-tetrasubstituted oxindole derivatives which are key structures for biological activities. The products are formed with a quaternary carbon and featured with two adjacent chiral centers. Various N -EDG(electron-donating group) and N -EWG(electron-withdrawing group) protected oxindoles, including 3-aryl and 3-alkyl substituted ones, have been evaluated with aromatic and aliphatic imines under this catalytic system, smoothly giving desired products in good yields as well as excellent diastereo- and enantioselectivities. [ABSTRACT FROM AUTHOR]

The catalytic enantioselective synthesis of 3-aryl-substituted pyrrolopyrimidines (PPYs), a common motif in drug discovery, is achieved through a kinetic resolution via quaternary ammonium salt-catalyzed nucleophilic aromatic substitution (SNAr). Both enantioenriched products and starting materials can be functionalized with no observed racemization to give enantiodivergent access to diverse chiral analogues of an important class of kinase inhibitor. One of the compounds was found to be a potent and selective inhibitor of breast tumor kinase. [ABSTRACT FROM AUTHOR]

Abstract: Isoxazolinone sind biologisch und synthetisch interessante, dicht funktionalisierte Heterocyclen, die lange Zeit nicht in enantiomerenangereicherter Form über asymmetrische Katalyse zugänglich waren. Neben dem Mangel an enantioselektiven Methoden ist die Funktionalisierung der Isoxazolinone oft durch Regioselektivitätsprobleme aufgrund der Konkurrenz mehrerer nukleophiler Zentren innerhalb der Heterocyclen erschwert. Hier beschreiben wir die erste regio‐ und enantioselektive C‐Allylierung von Isoxazolinonen. Diese verlief mit hoher Regioselektivität zugunsten eines linearen Allylierungsprodukts, obwohl Iridium‐Phosphoramidit‐Katalysatoren üblicherweise verzweigte Isomere bilden. Unsere Studien deuten darauf hin, dass dies eine Folge einer Reaktionskaskade ist. Eine anfängliche regio‐ und enantioselektive N‐Allylierung bildet ein verzweigtes Allylintermediat, und eine nachfolgende spontane [3,3]‐Umlagerung ermöglicht einen Chiralitätstransfer. [ABSTRACT FROM AUTHOR]

We report herein a dynamic kinetic resolution (DKR) involving ortho-quinone methide ( o-QM) intermediates. In the presence of Et3N and the cinchonine-derived nucleophilic catalyst D, the DKR of 2-sulfonylalkyl phenols with allenic esters afforded chiral benzylic sulfones in 57-79 % yield with good to excellent enantioselectivity (85-95 % ee). Furthermore, with 2-(tosylmethyl)sesamols or 2-(tosylmethyl)naphthols, from which stable o-QM substrates can be generated, a formal [4+2] cycloaddition delivered 4-aryl- or alkyl-substituted chromans with excellent enantioselectivity (88-97 % ee). [ABSTRACT FROM AUTHOR]

Helically chiral poly(quinoxaline-2,3-diyl)s bearing 4-aminopyrid-3-yl pendants were synthesized as new helical-polymer-based chiral nucleophilic organocatalysts. The obtained chiral nucleophilic polymer catalysts exhibited high catalytic activity, enantioselectivity, and reusability in asymmetric Steglich rearrangement of oxazolyl carbonate to C -carboxyazlactone. The polyquinoxaline-based, helically chiral DMAP catalyst mediated intramolecular acyl transfer selectively, by contrast with known small-molecule-based chiral organocatalysts, which also mediate intermolecular acyl transfers. [ABSTRACT FROM AUTHOR]

Density functional theory calculations were performed to validate the proposed reaction mechanism for the enantioselective nucleophilic borylation of a polarized C=O double bond in the presence of diphosphine/borylcopper(I) complexes. Consequently, we successfully elucidated the origin for the regioselectivity and the mechanism for the enantioselectivity of the reaction. We also obtained theoretical explanations for the fact that the presence of a proton source gave a higher reactivity and a better enantioselectivity in the borylation reaction of aldehydes with a copper(I)/(R)-DTBM-SEGPHOS complex catalyst. This study is particularly valuable toward the development and design of novel enantioselective borylation reactions with polarized carbon-heteroatom double bonds. [ABSTRACT FROM AUTHOR]

A new method for the preparation of optically active α-methylidene-γ-lactones is presented. The developed strategy utilizes an intramolecular Rauhut-Currier reaction for a facile construction of the α-methylidene-γ-lactone framework. The reaction is catalyzed by a chiral phosphine and employs the principles of nucleophilic catalysis. It benefits from operational simplicity and uses readily available starting materials. [ABSTRACT FROM AUTHOR]

An enantioselective N-heterocycliccarbene (NHC)-catalyzed dieneregenerative (4 + 2) annulation has been achieved through the useof highly nucleophilic morpholinone-derived catalysts. The reactionproceeds with good to excellent yields, high enantioselectivity (most>92% ee), and good diastereoselectivity (most >7:1). The generalityof the reaction is high, with 19 examples reported. The utility ofthe products has been examined with subsequent derivatization in Diels–Alderreactions using electron-poor dienophiles. Furthermore, interceptionof the proposed β-lactone intermediate has been achieved, allowingthe synthesis of compounds bearing four contiguous stereocenters withhigh levels of enantio- and diastereoselectivity. [ABSTRACT FROM AUTHOR]

The enantioselective addition of anilines to azoalkenes was accomplished through the use of a chiral phosphoric acid catalyst. The resulting α-arylamino hydrazones were obtained in good yields and excellent enantioselectivities and provide access to enantioenriched α-arylamino ketones. A serendipitous kinetic resolution of racemic α-arylamino hydrazones is also described. [ABSTRACT FROM AUTHOR]

Nucleophilic catalysts for a 1,6 addition/Nazarov cyclization/elimination sequence were evaluated for their ability to induce enantioselectivity in the electrocyclization step. Of the tertiary amines examined, it was found that a cinchona alkaloid derivative was able to generate substituted 5-hydroxy γ-methylene cyclopentenones with excellent enantioselectivity. The study results suggest that successful cyclization depends upon the ability of the dienyl diketone substrate to readily adopt an s - cis conformation. [ABSTRACT FROM AUTHOR]

A new type of chiral 5-aminoimidazole nucleophilic catalyst, designated as Alkyl-PDPI (PDPI=3-pyrrolidinyl-6,7-dihydro-5 H-pyrrolo[1,2- a]imidazole), was rationally designed, synthesized and applied to the kinetic resolution of various arylalkylcarbinols with good to excellent enantioselectivities. In particular, for phenyl( tert-butyl)methanol and 1-mesitylethanol, the s factors are as high as 45 and 67, respectively. Additionally, this new kind of chiral imidazole catalyst also showed good enantioselectivity for heteroarylalkylcarbinols. [ABSTRACT FROM AUTHOR]

Chiral triaryl phosphates promote the enantioselective iodolactonization of 4-substituted 4-pentenoic acids to give the corresponding iodolactones in high yields with high enantioselectivity. N-Chlorophthalimide (NCP) is employed as a Lewis acidic activator and oxidant of I2 for the present iodolactonization. In combination with 1.5 equivalents of NCP, only 0.5 equivalents of I2 are sufficient to generate the iodinating reagent. [ABSTRACT FROM AUTHOR]

In this article we describe a general catalytic procedure for the formation of β-lactones bearing two stereogenic centers, from disubstituted ketenes and achiral aldehydes. BINAPHANE was found to display excellent enantioselectivity (≥90% ee for eight examples) and good diastereoselectivity (≥90:10 for 13 examples) in catalyzing the formation of β-lactones bearing two stereogenic centers from achiral aldehydes (both aromatic and aliphatic) and alkylarylketenes or dialkylketenes. A preference for formation of the trans diastereomer was observed in these reactions. For those reactions where BINAPHANE failed as a catalyst, tri-n-butylphosphine was found to be an effective achiral nucleophilic catalyst, effecting good yield and diastereoselectivity in racemic β-lactone formation. Evidence for the involvement of phosphonium enolate intermediates in the reaction mechanism was obtained through reaction monitoring by 31P NMR spectroscopy and by comparison with previously characterized intermediates observed in the phosphine-catalyzed ketene homodimerization reaction. [ABSTRACT FROM AUTHOR]

Atom‐economic synthesis: The syn‐ and highly enantioselective Henry reactions of aliphatic aldehydes catalyzed by a readily available β‐amino alcohol copper catalyst were developed and successfully utilized in the synthesis of safingol. The ligand could be easily recovered without any racemization (see scheme). [ABSTRACT FROM AUTHOR]

The article focuses on a research paper on a single chiral Ni catalyst which could join two alkyl groups, controlling the orientations of the neighboring stereocenters, published in this issue. It highlights carbon-carbon bond formation between chiral alkyl centers. It suggests the development of a stereoconvergent cross-coupling of a racemic chiral alkyl nucleophile.

Organophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrolled synthesis of phosphorus-stereogenic centers is challenging and traditionally depends on a resolution or use of stochiometric auxiliaries. Herein, enantioenriched phosphorus centers have been synthesized using chiral nucleophilic catalysis. Racemic H-phosphinate species were coupled with nucleophilic alcohols under halogenating conditions. Chiral phosphonate products were synthesized in acceptable yields (33–95%) and modest enantioselectivity (up to 62% ee) was observed after identification of an appropriate chiral catalyst and optimization of the solvent, base, and temperature. Nucleophilic catalysis has a tremendous potential to produce enantioenriched phosphate mimics that could be used as prodrugs or chemical biology probes. [ABSTRACT FROM AUTHOR]

[Display omitted] • The features of asymmetric Ni(II)-catalyzed Michael addition of 1,3-dicarbonyl compounds to nitroolefins were investigated. • The critical role of hydrogen bond formation at the enantio-determining stage is shown on two examples examples. • The computational results confirmed by experimental data. The features of asymmetric Ni(II)-catalyzed Michael addition of 1,3-dicarbonyl compounds to nitroolefins has been investigated by DFT and experimental studies. The results support a mechanistic pathway that proceeds via formation of enolate, intramolecular nucleophilic attack on coordinated nitroolefin and protonation of resulting nitronate complex. The calculated difference in activation energies for the formation of enantiomeric Michael adducts in the case of diethyl malonate and ω-nitrostyrene are remarkably close to the experimental values, obtained from enantioselectivity-temperature dependence. The presence of H-bond in the ω-nitrostyrene complex induced further investigation of the reaction path of cinnamic aldehyde, thah cannot form such bond. Comparison of the energy profiles for ω-nitrostyrene and cynnamic aldehyde as Michael acceptors shows the important role of hydrogen bond formation between Ni complex and reagent for emergence of enantioselectivity. [ABSTRACT FROM AUTHOR]

An L-valine-derived phosphine is successfully applied as catalyst for the intramolecular Rauhut-Currier reaction of acrylates (I) and (III) leading to chiral α-methylidene-δ-lactones (II) and (IV), respectively. [ABSTRACT FROM AUTHOR]