Excellent Ee Research Articles

Efficient Synthesis of Chiral Trisubstituted 1,2‐Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes

AbstractAn N,N′‐dioxide/scandium(III) complex catalyzed, highly efficient conjugate addition of malonic esters to enynes is described. A range of trisubstituted 1,2‐allenyl ketones were obtained in high yields (up to 99 %) with good d.r. (up to 95/5) and excellent ee values (97 %–99 %). Moreover, the products could be easily transformed into chiral furan and 5‐hydroxypyrazoline derivatives, both of which are important skeletons of many biologically active compounds and pharmacologicals.

Efficient Synthesis of Chiral Trisubstituted 1,2-Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes.

An N,N′‐dioxide/scandium(III) complex catalyzed, highly efficient conjugate addition of malonic esters to enynes is described. A range of trisubstituted 1,2‐allenyl ketones were obtained in high yields (up to 99 %) with good d.r. (up to 95/5) and excellent ee values (97 %–99 %). Moreover, the products could be easily transformed into chiral furan and 5‐hydroxypyrazoline derivatives, both of which are important skeletons of many biologically active compounds and pharmacologicals.

Nickel-Catalyzed Borylation of Benzylic Ammonium Salts: Stereospecific Synthesis of Enantioenriched Benzylic Boronates.

We have developed a stereospecific, nickel-catalyzed cross-coupling of secondary benzylic ammonium salts and diboronate esters to deliver highly enantioenriched benzylic boronates. This reaction utilizes amine-derived electrophiles, which are readily available in high enantiopurity, and simple, inexpensive nickel catalysts. This reaction has broad scope, enabling synthesis of a variety of secondary benzylic boronates in good yields and excellent ee's.

Heterogeneous Dipeptide‐Catalyzed α‐Amination of Aldehydes in a Continuous‐Flow Reactor: Effect of Residence Time on Enantioselectivity

AbstractA solid‐supported dipeptide‐catalyzed continuous‐flow process was developed for the direct enantioselective α‐amination of aldehydes with dibenzyl azodicarboxylate as the electrophilic nitrogen source. With residence time control as an efficient tool for the fine‐tuning of the enantioselectivity, synthetically useful α‐hydrazino alcohols were achieved with excellent ees. The packed‐bed system proved to be highly robust: no decrease in catalyst activity or selectivity was detected throughout 20 h of continuous‐flow operation.magnified image

ChemInform Abstract: Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod=1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

Enantioselective Synthesis of Spirocyclohexadienones by NHC-Catalyzed Formal [3+3] Annulation Reaction of Enals.

The enantioselective synthesis of pyrazolone-fused spirocyclohexadienones was demonstrated by the reaction of α,β-unsaturated aldehydes with α-arylidene pyrazolinones under oxidative N-heterocyclic carbene (NHC)catalysis. This atom-economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all-carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC-catalyzed generation of chiral α,β-unsaturated acyl azoliums from enals, and base-mediated tandem generation of dienolate/enolate intermediates from pyrazolinones.

Enantioselective Synthesis of Spirocyclohexadienones by NHC‐Catalyzed Formal [3+3] Annulation Reaction of Enals

AbstractThe enantioselective synthesis of pyrazolone‐fused spirocyclohexadienones was demonstrated by the reaction of α,β‐unsaturated aldehydes with α‐arylidene pyrazolinones under oxidative N‐heterocyclic carbene (NHC)catalysis. This atom‐economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all‐carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC‐catalyzed generation of chiral α,β‐unsaturated acyl azoliums from enals, and base‐mediated tandem generation of dienolate/enolate intermediates from pyrazolinones.

Organocopper‐Triggered Cyclisation of Conjugated Diene‐ynes: Diastereo‐ and Enantioselective Synthesis of Indenes

AbstractOrganocopper reagents react with readily available chiral conjugated diene‐ynes to give indene derivatives bearing two stereogenic centres. The investigation of this original reaction in optically pure series demonstrates that a double transfer of chirality is operating. A stereocontrolled cascade involving SN2′ followed by carbocupration and conjugate addition reactions accounts for the total recovery of the initial chirality. The scope and limitations of the reaction were investigated. The high diastereofacial discrimination in the cyclisation step allowed the construction of the quaternary stereocentre with excellent dr and ee, with the opposite configuration depending on the E‐ or Z‐configuration of the alkene in the starting material. Post‐functionalisation of indenes allowed the synthesis of indanyl derivatives containing four contiguous stereocentres.magnified image

Enantioselective Construction of Spiroindolines with Three Contiguous Stereogenic Centers and Chiral Tryptamine Derivatives via Reactive Spiroindolenine Intermediates.

The highly efficient synthesis of the enantioenriched spiroindolines by iridium-catalyzed asymmetric allylic dearomatization and reduction is presented. Spiroindolines containing three contiguous stereogenic centers were obtained with excellent diastereo- and enantioselectivity. In addition, a chiral tryptamine derivative could be easily accessed in good yield with excellent ee value through an unprecedented dearomatization/retro-Mannich/hydrolysis cascade reaction of an indole derivative.

Enantioselective Construction of Spiroindolines with Three Contiguous Stereogenic Centers and Chiral Tryptamine Derivatives via Reactive Spiroindolenine Intermediates

AbstractThe highly efficient synthesis of the enantioenriched spiroindolines by iridium‐catalyzed asymmetric allylic dearomatization and reduction is presented. Spiroindolines containing three contiguous stereogenic centers were obtained with excellent diastereo‐ and enantioselectivity. In addition, a chiral tryptamine derivative could be easily accessed in good yield with excellent ee value through an unprecedented dearomatization/retro‐Mannich/hydrolysis cascade reaction of an indole derivative.

Ruthenium‐Catalyzed Asymmetric Transfer Hydrogenation of Propargylic Ketones

AbstractThe asymmetric transfer hydrogenation of α,β‐propargyl ketones catalyzed by an in situ formed ruthenium–hydroxyamide complex was explored. The acetylenic alcohols were isolated in good to excellent yields with excellent ee values (typically >90 %) after short reaction times at room temperature.

Ligand Control of Diastereodivergency in Asymmetric Inverse Electron Demand Diels–Alder Reaction

A diastereodivergent direct catalytic asymmetric inverse electron demand Diels–Alder reaction between ketenes and 3-alkylenyloxindoles was accomplished by using chiral N,N′-dioxide/gadolinium complexes. By adjusting only the substituents of the ligand and retaining other catalysis conditions, both syn- and anti-indole-fused dihydropyranones bearing two vicinal stereogenic centers were obtained in high yields with excellent ee values. Thus, by changing the configuration of the chiral ligands, all stereoisomers could be obtained from the same set of starting materials.

ChemInform Abstract: Highly Efficient Dynamic Kinetic Resolution of Benzylic Amines with Palladium Catalysts on Oxidized Multiwalled Carbon Nanotubes for Racemization.

AbstractThe title process provides benzylic amides in high yields with excellent ee.

Synthesis of BF₃ catalyzed Mannich derivatives with excellent ee from phenylpropanolamine, study of their antimicrobial activity and molecular docking.

Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.

Prolinamide‐Derived Ionic‐Liquid‐Supported Organocatalyst for Asymmetric Mono‐ and Bis‐Aldol Reactions in the Presence of Water

AbstractA novel recyclable prolinamide‐derived ionic‐liquid‐supported organocatalyst of asymmetric cross‐aldol reactions in aqueous medium has been developed. In its presence, aromatic aldehydes react with cyclic or linear ketones to afford chiral aldol adducts in moderate to high yields and with excellent dr (anti/syn up to 96:4) and ee (81–99 %) values that do not tend to decline over ten recycles of the catalyst. Furthermore, it allows a highly enantioselective catalytic synthesis of linear bis‐aldols in aqueous medium.

An Enantioselective Synthesis of Spirobilactams through Copper‐Catalyzed Intramolecular Double N‐Arylation and Phase Separation

AbstractSpirobicyclic structures are versatile building blocks for functional chiral molecules. An enantioselective synthesis of chiral spirobilactams via a copper‐catalyzed double N‐arylation was developed. Amplification of solution ee by in situ precipitation of the racemate was observed with this method and enantioenriched spirobilactams were obtained with excellent ee values through simple solid–solution phase separation.

An Enantioselective Synthesis of Spirobilactams through Copper-Catalyzed Intramolecular Double N-Arylation and Phase Separation.

Spirobicyclic structures are versatile building blocks for functional chiral molecules. An enantioselective synthesis of chiral spirobilactams via a copper-catalyzed double N-arylation was developed. Amplification of solution ee by in situ precipitation of the racemate was observed with this method and enantioenriched spirobilactams were obtained with excellent ee values through simple solid-solution phase separation.

A Single Lipase‐Catalysed One‐Pot Protocol Combining Aminolysis Resolution and Aza‐Michael Addition: An Easy and Efficient Way to Synthesise β‐Amino Acid Esters

AbstractA novel one‐pot protocol combining aza‐Michael addition and aminolysis resolution was developed to obtain chiral β‐amino acid esters with lipase B from Candida antarctica (CAL‐B) as the only catalyst. This method is conducted under mild reaction conditions and is very easy to handle. After a series of detailed optimization studies, ten racemic aromatic or aliphatic amines were subjected to this one‐pot procedure, and twelve chiral β‐amino acid esters and ten chiral amides were successfully synthesised with excellent ee values in theoretical yields. Scaled‐up procedures also worked without apparent reduction in reaction rate or enantioselectivity, which makes this method suitable for large‐scale production of chiral β‐amino acid esters.

Enantioselective and Regiodivergent Copper-Catalyzed Electrophilic Arylation of Allylic Amides with Diaryliodonium Salts.

A catalytic enantioselective and regiodivergent arylation of alkenes is described. Chiral copper(II)bisoxazoline complexes catalyze the addition of diaryliodonium salts to allylic amides in excellent ee. Moreover, the arylation can be controlled by the electronic nature of the diaryliodonium salt enabling the preparation of nonracemic diaryloxazines or β,β′-diaryl enamides.

Enantioselective Synthesis of Pyrrole-Based Spiro- and Polycyclic Derivatives by Iridium-Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.