Chiral DMAP‐N‐oxides as Acyl Transfer Catalysts: Design,Synthesis, and Application in Asymmetric Steglich Rearrangement

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.     

Exploration of a Chiral Cobalt Catalyst for Visible‐Light‐Induced Enantioselective Radical Conjugate Addition

Chiral catalysts tolerating photochemical reactions are in great demand for the vast development of visible‐light‐induced asymmetric synthesis. Now, chiral octahedral complexes based on earth‐abundant metal and chiral N₄ ligands are reported. One well‐defined chiral Co^II‐complex is shown to be an efficient catalyst in the visible‐light‐induced conjugated addition of enones by alkyl and acyl radicals, providing synthetically valued chiral ketones and 1,4‐dicarbonyls in 47–>99 % yields with up to 97:3 e.r.     

Stereocontrol of All‐Carbon Quaternary Centers through Enantioselective Desymmetrization of Meso Primary Diols by Organocatalyzed Acyl Transfer

The symmetry breaking of meso primary diols bearing a tetrahydropyran ring was employed, using catalytic asymmetric acyl transfer, to control all‐carbon quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect combining a desymmetrization step and a kinetic resolution. Moreover, a beneficial effect was exhibited by C₆F₆ solvent, yielding the first example of an organocatalyzed asymmetric acyl transfer. The desymmetrized monoesters were then used to obtain, after a straightforward ring opening sequence, complex polyketide building blocks bearing all‐carbon quaternary stereocenters.     

Bimetallic Catalytic Asymmetric Tandem Reaction of β‐Alkynyl Ketones to Synthesize 6,6‐Spiroketals

The enantioselective tandem reaction of β,γ‐unsaturated α‐ketoesters with β‐alkynyl ketones was realized by a bimetallic catalytic system of achiral Au^ΙΙΙ salt and chiral N,N′‐dioxide‐Mg^ΙΙ complex. The cycloisomerization of β‐alkynyl ketone and asymmetric intermolecular [4+2] cycloaddition with β,γ‐unsaturated α‐ketoesters subsequently occurred, providing an efficient and straightforward access to chiral multifunctional 6,6‐spiroketals in up to 97 % yield, 94 % ee and >19/1 d.r. Besides, a catalytic cycle was proposed based on the results of control experiments.     

Kinetic Resolution of Racemic Mandelic Acid Esters by N,N′‐Dioxide–Scandium‐Complex‐Catalyzed Enantiomer‐Selective Acylation

A simple and efficient acylative kinetic resolution of racemic mandelic acid esters was accomplished with a chiral N,N’‐dioxide–scandium(III) complex under mild and base‐free reaction conditions. A variety of mandelic acid esters performed well in the reaction, obtaining both acylated products (up to 49% yield, 97% ee) and recovered substrates (up to 49% yield, 95% ee) in high enantioselectivities with perfect selectivity factors (up to 247). The enantioselective recognition and catalytic models were also proposed for the catalytic KR reaction.     

Asymmetric Ring‐Opening of Cyclopropyl Ketones with Thiol,Alcohol, and Carboxylic Acid Nucleophiles Catalyzed by a Chiral N,N′‐Dioxide–Scandium(III) Complex

A highly efficient asymmetric ring‐opening reaction of cyclopropyl ketones with a broad range of thiols, alcohols and carboxylic acids has been first realized by using a chiral N,N′‐dioxide–scandium(III) complex as catalyst. The corresponding sulfides, ethers, and esters were obtained in up to 99 % yield and 95 % ee. This is also the first example of one catalytic system working for the ring‐opening reaction of donor–acceptor cyclopropanes with three different nucleophiles, let alone in an asymmetric version.     

Enantioselective Copper‐Catalyzed Alkylation of Quinoline N‐Oxides with Vinylarenes

An asymmetric copper‐catalyzed alkylation of quinoline N ‐oxides with chiral Cu–alkyl species, generated by migratory insertion of a vinylarene into a chiral Cu−H complex, is reported. A variety of quinoline N ‐oxides and vinylarenes underwent this Cu‐catalyzed enantioselective alkylation reaction, affording the corresponding chiral alkylated N‐heteroarenes in high yield with high‐to‐excellent enantioselectivity. This enantioselective protocol represents the first general and practical approach to access a wide range of chiral alkylated quinolines.     

Asymmetric Transfer Hydrogenation Catalyzed by Mesoporous MCM‐41‐Supported Chiral Ru‐Complex

Chiral N‐sulfonyldiamine was successfully anchored on mesoporous MCM‐41 silica. The MCM‐41‐supported chiral N‐sulfonyldiamine was used as an efficient heterogeneous chiral ligand in the asymmetric transfer hydrogenation of ketones. This heterogeneous system offered satisfactory enantioselectivities up to 94 % with excellent conversions.     

New Chiral Ligand N—Toluenesulfony1—2,2‘—dimethoxy—6,6’—di—aminobiphenyl for Catalytic Asymmetric Transfer Hydrogenation of Ketones

A new chiral ligand N‐p‐toluenesulfonyl‐2,2′‐dimethoxy‐6,6′‐diaminobiphenyl (Ts‐DMBDPPA) was prepared from 2,2′‐dimethoxy‐6,6′‐diaminobiphenyl via N‐tosylation. Its Ru(II) complex was effective catalysts for catalytic asymmetric transfer hydrogenation of aromatic ketones (with ee's up to 69.3%).     

Asymmetric Synthesis of 2,3‐Dihydropyrroles by Ring‐Opening/Cyclization of Cyclopropyl Ketones Using Primary Amines

The asymmetric ring‐opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′‐dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3‐dihydropyrroles as well as an effective procedure for the kinetic resolution of 2‐substituted cyclopropyl ketones.     

Asymmetric Catalytic Formal 1,4‐Allylation of β,γ‐Unsaturated α‐Ketoesters: Allylboration/Oxy‐Cope Rearrangement

A highly enantioselective formal conjugate allyl addition of allylboronic acids to β,γ‐unsaturated α‐ketoesters has been realized by employing a chiral Ni^II/N,N′‐dioxide complex as the catalyst. This transformation proceeds by an allylboration/oxy‐Cope rearrangement sequence, providing a facile and rapid route to γ‐allyl‐α‐ketoesters with moderate to good yields (65–92 %) and excellent ee values (90–99 % ee). The isolation of 1,2‐allylboration products provided insight into the mechanism of the subsequent oxy‐Cope rearrangement reaction: substrate‐induced chiral transfer and a chiral Lewis acid accelerated process. Based on the experimental investigations and DFT calculations, a rare boatlike transition‐state model is proposed as the origin of high chirality transfer during the oxy‐Cope rearrangement.     

Synthesis of Enantiomerically Pure 1,2,3,4‐Tetrahydro‐β‐carbolines and N‐Acyl‐1‐aryl Ethylamines by Rhodium‐Catalyzed Hydrogenation

The rhodium‐catalyzed asymmetric hydrogenation of different enamides, in particular, dihydro‐β‐carboline derivates, was investigated in the presence of chiral phosphorus ligands. Enantioselectivities of up to 99 % ee were obtained after ligand screening and optimization of the reaction conditions. The scope and limitation of the catalysts were shown in the synthesis of optically active tetrahydro‐β‐carbolines and other benchmark N‐acyl‐1‐aryl ethylamines.     

Asymmetric Ring Opening/Cyclization/Retro‐Mannich Reaction of Cyclopropyl Ketones with Aryl 1,2‐Diamines for the Synthesis of Benzimidazole Derivatives

A highly efficient asymmetric ring‐opening/cyclization/retro‐Mannich reaction of cyclopropyl ketones with aryl 1,2‐diamines has been realized using a chiral N,N′‐dioxide/Sc^III catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole‐substituted amide and cycloheptene derivatives.     

Design,Synthesis, and Application of Chiral C2‐Symmetric Spiroketal‐Containing Ligands in Transition‐Metal Catalysis

We present an expedient and economical route to a new spiroketal‐based C₂‐symmetric chiral scaffold, termed SPIROL. Based on this spirocyclic scaffold, several chiral ligands were generated. These ligands were successfully employed in an array of stereoselective transformations, including in iridium‐catalyzed hydroarylations (up to 95 % ee), palladium‐catalyzed allylic alkylations (up to 97 % ee), intermolecular palladium‐catalyzed Heck couplings (up to 94 % ee), and rhodium‐catalyzed dehydroalanine hydrogenation (up to 93 % ee).     

BINOL Phosphoric Acid‐Catalyzed Asymmetric Mannich Reaction of Cyclic N‐Acyl Ketimines with Cyclic Enones

A highly enantio‐ and diastereoselective Mannich reaction of cyclic N‐acyl ketimines generated in situ from 3‐hydroxyisoindolin‐1‐ones with cyclic enones has been accomplished using a chiral phosphoric acid catalyst to afford the chiral isoindalinone derivatives in high yields with excellent enantioselectivities (upto 97 % ee). This is the first report on the synthesis of chiral isoindolin‐1‐ones bearing adjacent quaternary and tertiary stereogenic centers.     

Catalytic Asymmetric Synthesis of Trifluoromethylated γ‐Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives

Novel cinchona alkaloid derived chiral phase‐transfer catalysts enabled the highly chemo‐, regio‐, diastereo‐, and enantioselective umpolung addition of trifluoromethyl imines to α,β‐unsaturated N‐acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0 mol %, this new catalytic asymmetric transformation provides facile and high‐yielding access to highly enantiomerically enriched chiral trifluoromethylated γ‐amino acids and γ‐lactams.     

Asymmetric Synthesis of 2,4,5‐Trisubstituted Δ2‐Thiazolines

Δ²‐Thiazolines are interesting heterocycles that display a wide variety of biological characteristics. They are also common in chiral ligands used for asymmetric syntheses and as synthetic intermediates. Herein, we present asymmetric routes to 2,4,5‐trisubstituted Δ²‐thiazolines. These Δ²‐thiazolines were synthesized from readily accessible/commercially available α,β‐unsaturated methyl esters through a Sharpless asymmetric dihydroxylation and an O→N acyl migration reaction as key steps. The final products were obtained in good yields with up to 97 % enantiomeric excess.     

Enantioselective Synthesis of N,S‐Acetals by an Oxidative Pummerer‐Type Transformation using Phase‐Transfer Catalysis

Reported is the first enantioselective oxidative Pummerer‐type transformation using phase‐transfer catalysis to deliver enantioenriched sulfur‐bearing heterocycles. This reaction includes the direct oxidation of sulfides to a thionium intermediate, followed by an asymmetric intramolecular nucleophilic addition to form chiral cyclic N,S‐acetals with moderate to high enantioselectivites. Deuterium‐labelling experiments were performed to identify the stereodiscrimination step of this process. Further analysis of the reaction transition states, by means of multidimensional correlations and DFT calculations, highlight the existence of a set of weak noncovalent interactions between the catalyst and substrate that govern the enantioselectivity of the reaction.     

An Enantioselective CpxRh(III)‐Catalyzed C−H Functionalization/Ring‐Opening Route to Chiral Cyclopentenylamines

A chiral Cp^xRh^III catalyst system in situ generated from a Cp^xRh^I(cod) precatalyst and bis(o‐toluoyl) peroxide as activating oxidant was developed for a C?H activation/ring‐opening sequence between aryl ketoxime ethers and 2,3‐diazabicyclo[2.2.1]hept‐5‐enes. This transformation provides access to densely functionalized chiral cyclopentenylamines in excellent yields and enantioselectivities of up to 97:3 er. The reported method is also well suitable for asymmetric alkenyl C?H functionalizations of α,β‐unsaturated oxime ethers, furnishing skipped dienes with high levels of enantiocontrol.     

Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral‐at‐Rhodium Lewis Acid

A bis‐cyclometalated chiral‐at‐metal rhodium complex catalyzes the Diels–Alder reaction between N‐Boc‐protected 3‐vinylindoles (Boc=tert‐butyloxycarbonyl) and β‐carboxylic ester‐substituted α,β‐unsaturated 2‐acyl imidazoles with good‐to‐excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92–99 % ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2‐acyl imidazole dienophile by two‐point binding and overrules the preferred regioselectivity of the uncatalyzed reaction.