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An efficient catalytic asymmetric dearomatizing amination of 2-naphthols and phenols catalyzed by N,N′-dioxide-copper(I) complex as a chiral catalyst was presented. A variety of optically active β-naphthalenone compounds with a nitrogen-containing quaternary carbon stereocenter were obtained with high yield and enantioselectivity under mild reaction conditions. Mechanistic studies indicated that this Csp2–N dearomatizing coupling proceeds via 1,3-reductive elimination of phenolate-CuIII-amino intermediate in five-membered ring transition states. The origin of enantioselectivity has also been elucidated based on density functional theory calculations. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The design and synthesis of spirochroman‐2‐on‐4,1'‐indan‐7'‐ol (SCIOL) and its application for synthesizing chiral monophosphinite ligands are reported. The synthesis features a tandem double Friedel‐Crafts reaction/lactonization to construct the spiro framework and the desired racemic SCIOL was obtained via 6 steps with a total yield of 44.5%. Using an inclusion resolution with N‐benzylcinchonidinium chloride, the optical SCIOL could be obtained in good yields on a gram scale. The preliminary studies indicated that the corresponding chiral spiro monophosphinite ligands exhibit high catalytic activity and enantioselectivity (up to 94% ee) in the rhodium‐catalyzed asymmetric hydrogenation of N‐acetyl dehydroamino esters. These outcomes highlight the significant potential of SCIOL as a useful framework for the development of chiral spiro ligands. [ABSTRACT FROM AUTHOR]

The enantioselective addition of potent nucleophiles to ketenes poses challenges due to competing background reactions and poor stereocontrol. Herein, we present a method for enantioselective phosphoric acid catalyzed amination of ketenes generated from α‐aryl‐α‐diazoketones. Upon exposure to visible light, the diazoketones undergo Wolff rearrangement to generate ketenes. The phosphoric acid not only accelerates ketene capture by amines to form a single configuration of aminoenol intermediates but also promotes an enantioselective proton‐transfer reaction of the intermediates to yield the products. Mechanistic studies elucidated the reaction pathway and explained how the catalyst expedited the transformation and controlled the enantioselectivity. [ABSTRACT FROM AUTHOR]

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3)−H functionalization by hydrogen‐atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3)−H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3)−H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen‐atom transfer. [ABSTRACT FROM AUTHOR]

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high‐pKa Brønsted acid catalysts that enable free carbene insertion into N−H bonds of amines to prepare chiral α‐amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high‐energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high‐pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton‐transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol. [ABSTRACT FROM AUTHOR]

The first highly enantioselective intramolecular N−H bond insertion was realized by using copper catalysts modified with chiral spirobisoxazoline ligands, which provides a novel strategy for the synthesis of chiral 2-carboxytetrahydroquinolines. This reaction features fast reaction rate, high yield, high enantioselectivity, and mild reaction conditions. [ABSTRACT FROM AUTHOR]

The chiral tridentate spiro P-N-S ligands (SpiroSAP) were developed, and their iridium complexes were prepared. Introduction of a 1,3-dithiane moiety into the ligand resulted in a highly efficient chiral iridium catalyst for asymmetric hydrogenation of β-alkyl-β-ketoesters, producing chiral β-alkyl-β-hydroxyesters with excellent enantioselectivities (95-99.9 % ee) and turnover numbers of up to 355 000. [ABSTRACT FROM AUTHOR]

An iron-catalyzed asymmetric intramolecular cyclopropanation was realized in high yields and excellent enantioselectivity (up to 97 % ee) by using the iron complexes of chiral spiro-bisoxazoline ligands as catalysts. The superiority of iron catalysts exhibited in this reaction demonstrated the potential abilities of this sustainable metal in asymmetric carbenoid transformation reactions. [ABSTRACT FROM AUTHOR]

A highly enantioselective NH insertion reaction of α-diazoketones was developed by using cooperative catalysis by dirhodium(II) carboxylates and chiral spiro phosphoric acids. The insertion reaction provides a new access route to diverse chiral α-aminoketones, which are versatile building blocks in organic synthesis, with fast reaction rates, good yields and high enantioselectivity under mild and neutral conditions. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed asymmetric OH insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α-aryl-α-diazoacetates into the OH bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium-catalyzed asymmetric OH insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α-aryl-α-aryloxyacetates. [ABSTRACT FROM AUTHOR]

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

An efficient catalytic asymmetric hydrogenation of racemic α-arylcyclohexanones with an ethylene ketal group at the 5-position of the cyclohexane ring via dynamic kinetic resolution has been developed, giving chiral α-arylcyclohexanols with two contiguous stereocenters with up to 99% ee and >99:1 cis/ trans-selectivity. Using this highly efficient asymmetric hydrogenation reaction as a key step, (−)-α-lycorane was synthesized in 19.6% overall yield over 13 steps from commercially available starting material. [ABSTRACT FROM AUTHOR]

Efficient: A copper‐catalyzed enantioselective intramolecular insertion of carbenoids into phenolic OH bonds has been developed. This method can be used for the synthesis of the title compounds in high yields and excellent enantioselectivities under mild and neutral conditions (see scheme). NaBArF=sodium tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate. [ABSTRACT FROM AUTHOR]

A concise and efficient strategy has been developed to construct a polyketide chain by employing relay asymmetric hydrogenations catalyzed by two chiral spiro iridium catalysts. By using this strategy, an enantioselective total synthesis of (−)‐doliculide has been achieved in 19 steps with 6.9 % overall yield. The route features high enantioselectivity and diastereoselectivity. The catalyst loading can be as low as 0.005 mol‐%. It is convenient to obtain natural polyketides and their analogues by this strategy. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The design and synthesis of spirochroman‐2‐on‐4,1'‐indan‐7'‐ol (SCIOL) and its application for synthesizing chiral monophosphinite ligands are reported. The synthesis features a tandem double Friedel‐Crafts reaction/lactonization to construct the spiro framework and the desired racemic SCIOL was obtained via 6 steps with a total yield of 44.5%. Using an inclusion resolution with N‐benzylcinchonidinium chloride, the optical SCIOL could be obtained in good yields on a gram scale. The preliminary studies indicated that the corresponding chiral spiro monophosphinite ligands exhibit high catalytic activity and enantioselectivity (up to 94% ee) in the rhodium‐catalyzed asymmetric hydrogenation of N‐acetyl dehydroamino esters. These outcomes highlight the significant potential of SCIOL as a useful framework for the development of chiral spiro ligands. [ABSTRACT FROM AUTHOR]

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3)−H functionalization by hydrogen‐atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3)−H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3)−H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen‐atom transfer. [ABSTRACT FROM AUTHOR]

Abstract: A highly enantioselective rhodium-catalyzed hydrogenation of both (Z)- and (E)-β-arylenamides was developed by using monodentate chiral spiro phosphite and phosphine ligands, respectively. The hydrogenation reaction provides an efficient access to optically active β-arylisopropylamines, important building blocks for the synthesis of biologically active compounds. [Copyright &y& Elsevier]

Abstract: By using iridium catalyst based on chiral spiro phosphine–oxazoline ligands, the hydrogenation of α-arylcinnamic acids was accomplished under ambient pressure and low catalyst loading (as low as 0.01 mol %), providing useful 2,3-diarylpropionic acids in high yields with excellent enantioselectivities (up to 99% ee). A catalytic enantioselective synthesis of (S)-equol with the present hydrogenation reaction as a key step was accomplished starting from commercially available starting materials in six steps with 48.4% overall yield. [Copyright &y& Elsevier]