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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., (© 2023 Wiley-VCH GmbH.)

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp 3 )-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(sp 3 )-H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp 3 )-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., (© 2023 Wiley-VCH GmbH.)

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-pK a 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-pK a 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., (© 2023 Wiley-VCH GmbH.)

We have developed a nickel-catalyzed desymmetric reductive cyclization/coupling of 1,6-dienes. The reaction provides an efficient method for constructing a chiral tertiary alcohol and a quaternary stereocenter by a single operation. The method has excellent diastereoselectivity and high enantioselectivity, a broad substrate scope, as well as good tolerance of functional groups. Preliminary mechanism studies show that alkyl nickel(I) species are involved in the reaction., (© 2022 Wiley-VCH GmbH.)

A highly enantio- and regioselective hydrosulfonylation of 1,3-dienes with sulfonyl hydrazides has been realized by using a palladium catalyst containing a monodentate chiral spiro phosphoramidite ligand. The reaction provided an efficient approach to synthetically useful chiral allylic sulfones. Mechanistic studies suggest that the reaction proceeds through the formation of an allyl hydrazine intermediate and subsequent rearrangement to the chiral allylic sulfone product. The transformation of the allyl hydrazine intermediate to the product is the enantioselectivity-determining step., (© 2020 Wiley-VCH GmbH.)

A scalable enantioselective total synthesis of (-)-goniomitine has been developed by using an iridium-catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson-Claisen rearrangement, and one-pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (-)-goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)-1,2-dehydroaspidospermidine, (+)-aspidospermidine, and (+)-vincadifformine were also achieved., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A Brønsted acid enabled nickel-catalyzed hydroalkenylation of aldehydes and styrene derivatives has been developed. The Brønsted acid acts as a proton shuttle to transfer a proton from the alkene to the aldehyde, thereby leading to an economical and byproduct-free coupling. A series of synthetically useful allylic alcohols were obtained through one-step reactions from readily available styrene derivatives and aliphatic aldehydes in up to 88 % yield and with high linear selectivity., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A nickel(0)-catalyzed hydroalkenylation of imines with styrene and its derivatives is described. A wide range of aromatic and aliphatic imines directly coupled with styrene and its derivatives, thus providing various synthetically useful allylic amines with up to 95 % yield. The reaction offers a new atom- and step-economical approach to allylic amines by using alkenes instead of alkenyl-metallic reagents. Experiments and DFT calculations showed that TsNH 2 promotes the proton transfer from the coordinated olefin to the imine, accompanied by a new C-C bond formation., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A Ni-catalyzed hydroarylation of styrenes and 1,3-dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox-neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni-H was developed. The Ni-catalyzed hydroarylation, combined with a Ir-catalyzed C-H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A concise, divergent, asymmetric total syntheses of mulinane diterpenoids has been achieved. Specifically, a new strategy was developed featuring a key intramolecular Friedel-Crafts reaction to construct the chiral fused 5-6-6 tricyclic motif, followed by sequential Birch reduction, conjugate methylation, and homologation/ring-expansion reactions to furnish the desired 5-6-7 tricyclic skeleton bearing five contiguous stereocenters. With this efficient strategy, seven mulinane diterpenoids and two analogues were synthesized via late-stage functional modification or functionalization in 8.6-20 % overall yields and 11-15 steps., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A palladium-catalyzed hydrocarboxylation of alkynes with formic acid has been developed. The method provides acrylic acid and derivatives in good yields with high regioselectivity without the need to handle toxic CO gas., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF(-) =tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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. NaBAr(F)=sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chiral diols with three contiguous stereocenters were synthesized by a highly enantioselective ruthenium-catalyzed asymmetric hydrogenation of racemic α,α'-disubstituted cycloketones involving dynamic kinetic resolution. This new catalytic asymmetric method provides a concise route to the alkaloid (+)-γ-lycorane., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chiral acids: a highly enantioselective iridium-catalyzed hydrogenation of β,γ-unsaturated carboxylic acids is developed for the preparation of chiral 4-alkyl-4-aryl butanoic acids., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)