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Nickel-catalyzed intermolecular Heck reaction of cycloalkenes proceeds well with aryl triflates, mesylates and tosylates in excellent enantiomeric ratios. The asymmetric reductive Heck reaction also works with a 2-cyclopentenone ketal, which is equivalent to conjugate arylation of the enone itself. Economic Development Board (EDB) Accepted version We acknowledge financial supports from Peking University Shenzhen Graduate School, Shenzhen Bay Laboratory Insti- tute of Chemical Biology, Nanyang Technological University, GlaxoSmithKline and the Singapore Economic Development Board Trust Fund (2017 GSK-EDB Green and Sustainable Manufacturing Award) and A*STAR Science and Engineer- ing Research Council (A1783c0010).

Conformationally restricted azabicycles are becoming increasingly important in medicinal research. Asymmetric Heck bicyclization of enynes proceeds to give medicinally useful aza[3.1.0] and aza[4.1.0] bicycles with excellent enantioselectivity. The key organopalladium species after bicyclization can be trapped by silanes and terminal alkynes. Agency for Science, Technology and Research (A*STAR) Economic Development Board (EDB) Accepted version We acknowledge financial support from Peking UniversityShenzhen Graduate School, Shenzhen Bay Laboratory(21230011-Scripps), National Natural Science Foundation ofChina (NSFC 21933004), Nanyang Technological University,GSK-EDB Trust Fund (2017 GSK-EDB Green and Sustain-able Manufacturing Award) and A*STAR Science andEngineering Research Council (AME IRG A1783c0010).MP contributed DFT calculations.

Substituted cyclohexylamines are becoming increasingly important in drug discovery. Asymmetric Heck insertion/amination of nonconjugated cyclodienes proceeds to give 5-aryl cyclohexenylamines with good enantioselectivity and exclusive trans configurations. Primary and secondary anilines, indoline, and benzylamines are suitable amines. The weakly donating diphosphite Kelliphite forms a deep unsymmetrical pocket, which is essential for stereoselective anti attack of amines. Agency for Science, Technology and Research (A*STAR) Economic Development Board (EDB) Accepted version We acknowledge financial support from Peking UniversityShenzhen Graduate School, Shenzhen Bay Laboratory(21230011-Scripps), Nanyang Technological University,GSK-EDB Trust Fund (2017 GSK-EDB Green and Sustain-able Manufacturing Award) and A*STAR Science andEngineering Research Council (AME IRG A1783c0010).

We report a stereoselective conversion of terminal alkynes to α-chiral carboxylic acids using a nickel-catalyzed domino hydrocarboxylation-transfer hydrogenation reaction. A simple nickel/BenzP* catalyst displayed high activity in both steps of regioselective hydrocarboxylation of alkynes and subsequent asymmetric transfer hydrogenation. The reaction was successfully applied in enantioselective preparation of three nonsteroidal anti-inflammatory profens (>90 % ees) and the chiral fragment of AZD2716.

Copper complexes of monodentate phosphoramidites efficiently promote asymmetric arylation of N-azaaryl aldimines with arylboroxines. DFT calculations and experiments support an elementary step of 1,4-insertion in the reaction pathway, a step in which an aryl-copper species adds directly across four atoms of C=N-C=N in the N-azaaryl aldimines. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University We thank the Nanyang Technological University,GSK-EDBTrust Fund (GSK-EDB Green and Sustainable Manufactur-ing Award 2017), A*STAR Science &Engineering ResearchCouncil (AME IRG A1783c0010), City University of HongKong (7200534 and 9610369) and National Science Founda-tion of China (21502157) for financial support.

Asymmetric coupling proceeds efficiently between propargylic acetates, cycloalkenes and electron-rich heteroarenes including indoles, pyrroles, activated furans and thiophenes. 2,3-Disubstituted tetrahydrofurans and pyrrolidines are produced in trans configuration and excellent enantiomeric ratios. The reaction proceeds via Wacker-type attack of nucleophilic heteroarenes on alkenes activated by allenyl PdII species. Agency for Science, Technology and Research (A*STAR) Economic Development Board (EDB) Accepted version We acknowledge financial support from Peking University Shenzhen Graduate School, Shenzhen Bay Laboratory Institute of Chemical biology, Nanyang Technological University, GSK-EDB Trust Fund (2017 GSK-EDB Green and Sustain- able Manufacturing Award) and A*STAR Science and Engineering Research Council (AME IRG A1783c0010).

Asymmetric reductive amination of poorly nucleophilic sulfonamides was realized in the presence of nickel catalysts and titanium alkoxide. A wide range of ketones, including enolizable ketones and some biaryl ones, were converted into sulfonamides in excellent enantiomeric excess. The cyclization of sulfamates and intermolecular reductive amination of a diarylphosphinamide were also successful. Formic acid was used as a safe and economic surrogate of high-pressure hydrogen gas. Agency for Science, Technology and Research (A*STAR) Economic Development Board (EDB) We thank Singapore GSK-EDB Trust Fund (2017 GSK-EDBgreen and sustainable manufacturing award) and SingaporeA*STAR Science &Engineering Research Council (AMEIRG A1783c0010) for financial support. We thank BenAshley for some initial experiments.X.Z. and H.X. contrib-uted equally to the experiments.

Enantioselective α‐arylation of racemic ketones containing existing α′‐stereocenters is reported for the first time via base‐induced dynamic kinetic resolution. Bridged bicyclic rings are formed in good ee values, which are difficult to obtain otherwise. Furthermore, reactions in DMSO‐d6 resulted in extensive deuteration of both α‐ and α′‐positions in the products, thus supporting a pathway involving rapid, reversible deprotonation of ketones under catalytic conditions. MOE (Min. of Education, S’pore) Accepted version

Intermolecular alkylations of electron‐deficient arenes proceed with good para selectivity. Palladium catalysts were used to generate nucleophilic alkyl radicals from alkyl halides, which then directly add onto the arenes. The arene scope and the site of alkylation are opposite to those of classical Friedel–Crafts alkylations, which prefer electron‐rich systems. MOE (Min. of Education, S’pore) Accepted version

An asymmetric Heck annulation of propargylic acetates with several types of cyclic olefins affords highly strained cyclobutenes in high enantioselectivity.

A borrowing-hydrogen reaction between amines and alcohols is an atom-economic way to prepare alkylamines, ideally with water as the sole byproduct. Herein, nickel catalysts are used for direct N-alkylation of hydrazides and arylamines using racemic alcohols. Moreover, a nickel catalyst of (S)-binapine was used for an asymmetric N-alkylation of benzohydrazide with racemic benzylic alcohols.

A nickel‐catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium‐catalyzed process in that the nickel–carbon bond is converted into a C−H bond to release the product through protonation instead of hydride donation followed by C−H reductive elimination on Pd. MOE (Min. of Education, S’pore) Accepted version

Palladium-catalyzed three-component carboetherification of cyclic alkenes proceeded to give trans adducts exclusively with excellent enantioselectivity through a Wacker-type pathway. The reaction is also applicable to other oxygen nucleophiles, such as water, phenols, and carboxylic acids, as well as some electron-poor aryl amines. Agency for Science, Technology and Research (A*STAR) Economic Development Board (EDB) Accepted version We acknowledge financial support from Peking University Shenzhen Graduate School, Shenzhen Bay Laboratory (21230011-Scripps), Nanyang Technological University, the GSK-EDB Trust Fund (2017 GSK-EDB Green and Sustainable Manufacturing Award), and A*STAR Science and Engineering Research Council (AMEIRGA1783c0010)..

An asymmetric reductive amination of ketones using both arylamines and benzhydrazide in the presence of nickel catalysts was developed. A one-pot synthesis of tetrahydroquinoxalines was also developed starting directly from α-ketoaldehydes and 1,2-diaminobenzene. Formic acid was used as a safe and economic surrogate for high-pressure hydrogen gas. Strongly σ-donating bis(alkylphosphine)s are crucial ancillary ligands for both stereoselective hydride insertion and decarboxylation of the formate.

We report an efficient alkynylation reaction of aryl iodides with simultaneous ortho-alkylaton of aryl rings. The reaction between three simple reagents—aryl halides, alkynes, and alkyl halides—formed aryl–alkynyl bonds carrying hindered aryl rings in one step. The reaction proceeded via a Catellani-type pathway in the presence of norbornene. From a synthetic perspective, this reaction allows quick access toward many 1,2,3-substituted arenes and multiply substituted benzofurans, after manipulation of alkyne groups. These compounds are difficult to synthesize otherwise.

We report the use of nickel catalysts for the catalytic transfer hydrogenation of hydrazones and other ketimines with formic acid. Strongly donating bisphosphines must be used to support the catalysts. As in enzymatic catalysis, attractive weak interactions may be important for stereochemical control by the nickel/binapine catalyst.

A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.

A series of oxazole substrates and some analogues are successfully transformed to the synthetically and biologically important derivatives bearing a cyclopropane ring.

Asymmetric transfer hydrogenation of electron-deficient olefins is realized with nickel catalysts supported by strongly σ-donating bisphosphines. Deuterium labeling experiments point to a reaction sequence of formate decarboxylation, asymmetric hydride insertion and non-stereoselective protonation of resulting nickel enolates.

Alkylammonium salts in glycol are used as hydrogen-bond donors to promote halide dissociation under mild conditions.

We report the use of nickel catalysts for the catalytic transfer hydrogenation of hydrazones and other ketimines with formic acid. Strongly donating bisphosphines must be used to support the catalysts. As in enzymatic catalysis, attractive weak interactions may be important for stereochemical control by the nickel/binapine catalyst.

Many 1,3‐azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three‐membered rings is retained in the products. Thus, the cyclopropyl–halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway. MOE (Min. of Education, S’pore) Accepted version

A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.

The field of asymmetric (transfer) hydrogenation of prochiral olefins has been dominated by noble metal catalysts based on rhodium, ruthenium, and iridium. Herein we report that a simple nickel catalyst is highly active in the transfer hydrogenation using formic acid. Chiral α- and β-amino acid derivatives were obtained in good to excellent enantioselectivity. The key toward success was the use of the strongly donating and sterically demanding bisphosphine Binapine.

A general procedure for the fast Suzuki coupling of major families of heteroaryl bromides was realized by using Pd(OAc)2/PtBu3 as the catalyst. Many couplings were finished within minutes at room temperature in n-butanol. Different from previous studies, three typical heteroaryl bromides were systematically examined in couplings of various heteroaryl and aryl boronic acids.

Asymmetric reductive Heck reaction of aryl halides is realized in high stereoselectivity. Hydrogen-bond donors, trialkylammonium salts in a glycol solvent, were used to promote halide dissociation from neutral arylpalladium complexes to access cationic, stereoselective pathways.

The addition of an N–H bond to an olefin is the most direct route for the synthesis of alkylamines. Currently, intermolecular hydroamination is limited to reactions of a narrow range of reagents containing N–H bonds or activated alkenes, and all the examples of additions to unactivated alkenes require large excesses of alkene. We report intermolecular hydroamination reactions of indoles with unactivated olefins. The reactions occur with as few as 1.5 equiv of olefin to form N-alkylindoles exclusively and in good yield. Characterizations of the catalyst resting state, kinetic data, labeling studies, and computational data imply that the addition occurs by olefin insertion into the Ir–N bond of an N-indolyl complex and that this insertion reaction is faster than insertion of olefin into the Ir–C bond of the isomeric C-2-indolyl complex.

The field of asymmetric (transfer) hydrogenation of prochiral olefins has been dominated by noble metal catalysts based on rhodium, ruthenium, and iridium. Herein we report that a simple nickel catalyst is highly active in the transfer hydrogenation using formic acid. Chiral α- and β-amino acid derivatives were obtained in good to excellent enantioselectivity. The key toward success was the use of the strongly donating and sterically demanding bisphosphine Binapine.

Most existingmethods, however, were limited to formation of quaternarycenters. Coupling to form more common tertiary centersproved to be more difficult, because of fast product race-mization under basic conditions.To address this deficiency, the groups of MacMillan andGaunt independently reported copper-catalyzed arylation ofsilylketenimidesandenaminesformedinsitufromaldehydes.One silyl enolate derived from valerolactone can react withseveral diaryliodonium salts to give about 90% ee (Sche-me 1b).

). However, no product wasformed in the presence of LiOAc. With CsF, arylationoccurred, but the product racemized. To our delight, wefinally found that the tin enolate of 1-tetralone can couplevery efficiently with 91% ee when L1 was used. No erosion ofthe ee value was observed over time. The tin enolate wasformed easily by stirring alkenyl acetate with nBu

New ligand for old reaction: The title reaction of aryltriflates with aliphatic olefins leads to substitution at the internal position with high selectivity. The ratio of the desired isomer (shown in the scheme) to the sum of all other isomers is generally above 10:1. The key to success is the use of a ferrocene bisphosphine ligand (R= 1-naphthyl). The reaction can be easily scaled up, and minor isomers can be separated by chromatography.