Nickel‐Catalyzed Asymmetric Hydrogenation of 2‐Amidoacrylates

Earth‐abundant nickel, coordinated with a suitable chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2‐amidoacrylates, affording the chiral α‐amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000). The hydrogenated products could be simply converted into chiral α‐amino acids, β‐amino alcohols, and their bioactive derivatives. Furthermore, the catalytic mechanism was investigated using deuterium‐labeling experiments and computational calculations.     

Silver(I)‐Catalyzed Enantioselective [3+2]‐Cycloaddition Reaction of α‐Silylimines: A Facile Route to Quaternary‐Carbon‐Rich Scaffolds

A silver‐catalyzed highly enantioselective 1,3‐dipolar cycloaddition reaction of α‐silylimines with pyrone‐based trisubstituted olefins was developed affording bi‐ and tricyclic α‐quaternary‐carbon‐rich pyrano‐pyrrolidines in excellent yields. The tricyclic benzopyrone adducts thus obtained were efficiently transformed into highly complex tetracyclic scaffolds supporting four consecutive stereogenic centers with three quaternary carbons.     

Facile Synthesis of Spirooxindole‐Cyclohexenes via Phosphine‐Catalyzed [4 + 2] Annulation of α‐Substituted Allenoates

A phosphine‐catalyzed [4 + 2] annulation of α ‐substituted allenoate with exocyclic alkene moiety of oxindoles or indan‐1,3‐diones has been developed. Thus, under the catalysis of PPh₃ (20 mol%), a series of spirooxindole‐ or spiroindan‐1,3‐dione‐cyclohexenes have been obtained in moderate to excellent yields and regioselectivity from the annulations of α ‐methyl allenoates with 3‐methyleneoxindoles or 2‐methyleneindan‐1,3‐diones. This method offers an easy access to structurally novel spirocyclohexenes.     

Highly Enantioselective Iridium‐Catalyzed Hydrogenation of α,β‐Unsaturated Esters

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.     

Iridium‐Catalyzed Enantioselective Allylic Substitution of Unstabilized Enolates Derived from α,β‐Unsaturated Ketones

We report Ir‐catalyzed, enantioselective allylic substitution reactions of unstabilized silyl enolates derived from α,β‐unsaturated ketones. Asymmetric allylic substitution of a variety of allylic carbonates with silyl enolates gave allylated products in 62–94 % yield with 90–98 % ee and >20:1 branched‐to‐linear selectivity. The synthetic utility of this method was illustrated by the short synthesis of an anticancer agent, TEI‐9826.     

Iridium(I)‐catalyzed C−H Borylation of α,β‐Unsaturated Esters with Bis(pinacolato)diboron

A new process has been developed for the iridium(I)‐catalyzed vinylic C?H borylation of α,β‐unsaturated esters with bis(pinacolato)diboron (B₂pin₂). These reactions proceeded in octane at temperatures in the range of 80–120 °C to afford the corresponding alkenylboronic compounds in high yields with excellent regio‐ and stereoselectivities. The presence of an aryl ester led to significant improvements in the yields of the acyclic alkenylboronates. Crossover experiments involving deuterated substrates as well as a mixture of stereoisomers confirmed that this reaction proceeds via a 1,4‐addition/β‐hydride elimination mechanism. Notably, this reaction was also used to develop a one‐pot borylation/Suzuki–Miyaura cross‐coupling procedure.     

Ketenimines from Isocyanides and Allyl Carbonates: Palladium‐Catalyzed Synthesis of β,γ‐Unsaturated Amides and Tetrazoles

The reaction of allyl ethyl carbonates with isocyanides in the presence of a catalytic amount of Pd(OAc)₂ provided ketenimines through β‐hydride elimination of the allyl imidoylpalladium intermediates. The insertion of the isocyanide into the π‐allyl Pd complex proceeded via an unusual η¹‐allyl Pd species. The resulting ketenimines were hydrolyzed to β,γ‐unsaturated carboxamides during purification by flash column chromatography on silica gel or converted in situ into 1,5‐disubstituted tetrazoles by [3+2] cycloaddition with hydrazoic acid or trimethylsilyl azide.     

Gold(I)‐Catalyzed Dearomative [2+2]‐Cycloaddition of Indoles with Activated Allenes: A Combined Experimental–Computational Study

The gold‐catalyzed synthesis of methylidene 2,3‐cyclobutane‐indoles is documented through a combined experimental/computational investigation. Besides optimizing the racemic synthesis of the tricyclic indole compounds, the enantioselective variant is presented to its full extent. In particular, the scope of the reaction encompasses both aryloxyallenes and allenamides as electrophilic partners providing high yields and excellent stereochemical controls in the desired cycloadducts. The computational (DFT) investigation has fully elucidated the reaction mechanism providing clear evidence for a two‐step reaction. Two parallel reaction pathways explain the regioisomeric products obtained under kinetic and thermodynamic conditions. In both cases, the dearomative C?C bond‐forming event turned out to be the rate‐determining step.     

Asymmetric Synthesis of Spiropyrazolones through Phosphine‐Catalyzed [4+1] Annulation

An enantioselective synthesis of spiropyrazolones from allenoate‐derived MBH acetates and pyrazolones through a phosphine‐mediated [4+1] annulation process has been developed. Spiropyrazolones were readily prepared in good chemical yields and good to high enantioselectivities. This is the first asymmetric example in which α‐substituted allenoates were utilized as a C₄ synthon for phosphine‐catalyzed [4+1] annulation.     

Secondary Amine‐Catalyzed Asymmetric γ‐Alkylation of α‐Branched Enals via Dienamine Activation

The direct and enantioselective γ‐alkylation of α‐substituted α,β‐unsaturated aldehydes proceeding under dienamine catalysis is described. We have found that the Seebach modification of the diphenyl‐prolinol silyl ether catalyst in combination with saccharin as an acidic additive promotes an S_N1 alkylation pathway, while ensuring complete γ‐site selectivity and a high stereocontrol. Theoretical and spectroscopic investigations have provided insights into the conformational behavior of the covalent dienamine intermediate derived from the condensation of 2‐methylpent‐2‐enal and the chiral amine. Implications for the mechanism of stereoinduction are discussed.     

Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation

Indole synthesis by a gold(I)‐catalyzed intermolecular formal [4+2] reaction between 1,3‐diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3‐diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7‐disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.     

Palladium‐Catalyzed Asymmetric [4+2] Cycloaddition of 2‐Methylidenetrimethylene Carbonate with Alkenes: Access to Chiral Tetrahydropyran‐Fused Spirocyclic Scaffolds

A palladium‐catalyzed asymmetric [4+2] cycloaddition of 2‐methylidenetrimethylene carbonate with alkenes derived from pyrazolones, indandione, or barbiturate has been successfully developed, affording pharmacologically interesting chiral tetrahydropyran‐fused spirocyclic scaffolds. The target compounds were generated in good to excellent yields and with high enantioselectivity (up to 99 % ee). Furthermore, this cycloaddition reaction could be efficiently scaled up, and several synthetic transformations were accomplished for the construction of other useful chiral spiropyrazolone and spiroindandione derivatives.     

Manganese‐Catalyzed anti‐Selective Asymmetric Hydrogenation of α‐Substituted β‐Ketoamides

A Mn‐catalyzed diastereo‐ and enantioselective hydrogenation of α‐substituted β‐ketoamides has been realized for the first time under dynamic kinetic resolution conditions. anti‐α‐Substituted β‐hydroxy amides, which are useful building blocks for the synthesis of bioactive molecules and chiral drugs, were prepared in high yields with excellent selectivity (up to >99 % dr and >99 % ee) and unprecedentedly high activity (TON up to 10000). The origin of the excellent stereoselectivity was clarified by DFT calculations.     

Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters

A catalytic asymmetric intramolecular homologation of simple ketones with α‐diazoesters was firstly accomplished with a chiral N,N′‐dioxide–Sc(OTf)₃ complex. This method provides an efficient access to chiral cyclic α‐aryl/alkyl β‐ketoesters containing an all‐carbon quaternary stereocenter. Under mild conditions, a variety of aryl‐ and alkyl‐substituted ketone groups reacted with α‐diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β‐ketoesters in high yield and enantiomeric excess.     

Efficient Synthesis of N‐Alkylated 4‐Pyridones by Copper‐Catalyzed Intermolecular Asymmetric Propargylic Amination

Copper‐catalyzed intermolecular asymmetric propargylic amination with 4‐hydroxypyridines has been realized for the first time. In the presence of Cu complex derived from Pybox ligand, the N‐propargylated 4‐pyridones were obtained under mild reaction conditions with up to 99 % yield and 95 % ee. The Pybox ligand bearing a 4‐F‐phenyl substituent plays a key role for the high enantioselectivity. The products can be easily transformed to the core structure of quinolizidine alkaloids.     

Helical Poly(α,β‐unsaturated ketone) with Bulky Pendant of Binaphthyl from Anionic Polymerization of ((−)‐Menthyl (S)‐6′‐Acrylyl‐2′‐methyloxy‐1,1′‐binaphthalene‐2‐carboxylate

((?)‐Menthyl (S)‐6′‐acrylyl‐2′‐methyloxy‐1,1′‐binaphthalene‐2‐carboxylate ( 3 ) was synthesized and anionically polymerized using n‐BuLi as an initiator in toluene. The monomer 3 was levorotatory and had an [α]_D²⁵ value of ?72.4, but its corresponding polymer poly‐ 3 was dextrorotatory and showed an [α]_D²⁵ value of +162.0. Poly‐ 3 was confirmed to exist in the form of one‐handed helical structure in solution by means of comparing the specific optical rotation and the CD spectra with that of 3 and the model compounds such as (?)‐menthyl (S)‐6′‐propionyl‐2′‐methyloxy‐1,1′‐binaphthalene‐2‐carboxylate 2b and (?)‐menthyl (S)‐6′‐heptanoyl‐2′‐methyloxy‐1,1′‐binaphthalene‐2‐carboxylate 2c . This conclusion was also confirmed by the fact that the g‐value of poly‐ 3 is about 11 times of that of monomer 3 .