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.     

Asymmetric Diels–Alder Cycloadditions of Trifluoromethylated Dienophiles Under Trienamine Catalysis

β‐Trifluoromethyl (CF₃) enones were proved to act as good dienophiles in asymmetric normal‐electron‐demand Diels–Alder cycloadditions with 2,4‐dienals under trienamine catalysis with a chiral secondary amine. The sequential reductive amination transformations with benzylamine produced cis‐ and trans‐fused chiral trifluoromethylated octahydroisoquinolines in a diastereodivergent manner by using NaBH(OAc)₃ and NaBH₃CN as the reductants, respectively. Moreover, other types of activated alkenes that bear a CF₃ group have also been successfully utilized to construct a diverse range of chiral cyclic frameworks in high stereoselectivity.     

Rhodium(I)‐Catalyzed Enantioselective Cyclization of Enynes by Intramolecular Cleavage of the Rh−C Bond by a Tethered Hydroxy Group

Rhodium(I)‐catalyzed enantioselective intramolecular cyclization of enynes having a hydroxy group in the tether was investigated, and various cyclic compounds possessing a chiral quaternary carbon center were obtained in high yields with high ees. In this cyclization, a Rh?C(sp²) bond in the rhodacyclopentene intermediate, which was formed by enantioselective oxidative cycloaddition of enynes to a chiral rhodium(I) complex, was intramolecularly cleaved by σ‐bond metathesis of a tethered O?H bond in the substrate. Furthermore, it was found that the cyclic compounds were obtained with high ees even when the starting materials having a racemic secondary alcohol moiety were used in this reaction.     

Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2‐Hydroxypyrimidine/Pyrimidin‐2(1H)‐one Tautomers

A facile access to optically active cyclic ureas was developed through palladium‐catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy group with up to 99 % ee. Mechanistic studies indicated that reaction pathway proceed through hydrogenation of C=N of the oxo tautomer pyrimidin‐2(1H)‐one, acid‐catalyzed isomerization of enamine–imine, and hydrogenation of imine pathway. In addition, the chiral cyclic ureas are readily converted into useful chiral 1,3‐diamine and thiourea derivatives without loss of optical purity.     

Construction of a Chiral Silicon Center by Rhodium‐Catalyzed Enantioselective Intramolecular Hydrosilylation

Rhodium‐catalyzed enantioselective desymmetrizing intramolecular hydrosilylation of symmetrically disubstituted hydrosilanes is described. The original axially chiral phenanthroline ligand (S)‐BinThro (Binol‐derived phenanthroline) was found to work as an effective chiral catalyst for this transformation. A chiral silicon stereogenic center is one of the chiral motifs gaining much attention in asymmetric syntheses and the present protocol provides cyclic five‐membered organosilanes incorporating chiral silicon centers with high enantioselectivities (up to 91 % ee). The putative active Rh^I catalyst takes the form of an N,N,O‐tridentate coordination complex, as determined by several complementary experiments.     

Synthesis of chiral iridium complexes immobilized on amphiphilic polymers and their application to asymmetric catalysis

This article details the enantioselective catalytic performance of crosslinked, polymer immobilized, Ir‐based, chiral complexes for transfer hydrogenation of cyclic imines to chiral amines. Polymerization of the achiral vinyl monomer, divinylbenzene, and a polymerizable chiral 1,2‐diamine monosulfonamide ligand followed by complexation with [IrCl₂Cp*]₂ affords the crosslinked polymeric chiral complex, which can be successfully applied to asymmetric transfer hydrogenation of cyclic imines. Polymeric catalysts prepared from amphiphilic achiral monomers have high catalytic activity in the reaction and can be used both in organic solvents and water to give chiral cyclic amines with a high level of enantioselectivity (up to 98% ee). The asymmetric reaction allows for reuse of the heterogeneous catalyst without any loss in activity or enantioselectivity over several runs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3037–3044     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Phosphine‐Catalyzed [4+2] Cycloadditions of Allenic Ketones: Enantioselective Synthesis of Functionalized Tetrahydropyridines

Amino‐acid‐derived phosphine catalyzed [4+2] cycloaddition leading to chiral tetrahydropyridines, making use of α‐substituted allenic ketones as “C4 synthons” and N‐sulfonyl cyclic ketimines, has been developed. This asymmetric cycloaddition tolerates a wide range of α‐substituted allenic ketones. A series of chiral sultam‐fused tetrahydropyridines bearing a quaternary stereocenter were obtained in high yields with good enantioselectivities.     

Asymmetric Synthesis of Axially Chiral 2‐Aminobiaryls by Rhodium‐Catalyzed Benzannulation of 1‐Arylalkynes with 2‐(Cyanomethyl)phenylboronates

Asymmetric benzannulation of 1‐arylalkynes, where the aryl group is an ortho‐substituted aromatic group, with 2‐(cyanomethyl)phenylboronate was catalyzed by a rhodium complex coordinated with a chiral diene ligand to give high yields of axially chiral 2‐aminobiaryls with greater than 90 % ee.     

Organocatalytic Enantioselective Decarboxylative Reaction of Malonic Acid Half Thioesters with Cyclic N‐Sulfonyl Ketimines by Using N‐Heteroarenesulfonyl Cinchona Alkaloid Amides

The organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half thioesters (MAHTs) with cyclic N‐sulfonyl ketimines by using N‐heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic addition of the MAHTs to the ketimines prior to decarboxylation.     

Rhodium(III)‐Catalyzed Enantiotopic C−H Activation Enables Access to P‐Chiral Cyclic Phosphinamides

Compounds with stereogenic phosphorus atoms are frequently used as ligands for transition‐metal as well as organocatalysts. A direct catalytic enantioselective method for the synthesis of P ‐chiral compounds from easily accessible diaryl phosphinamides is presented. The use of rhodium(III) complexes equipped with a suitable atropochiral cyclopentadienyl ligand is shown to enable an enantiodetermining C−H activation step. Upon trapping with alkynes, a broad variety of cyclic phosphinamides with a stereogenic phosphorus(V) atom are formed in high yields and enantioselectivities. Moreover, these can be reduced enantiospecifically to P ‐chiral phosphorus(III) compounds.     

New Chiral Calixsalen Chromium Complexes: Recyclable Asymmetric Catalysts

A chiral N,N′‐bis(salicylidene)ethylenediamine (salen) polymer has been prepared by a condensation reaction between a thiophenedisalicyladehyde derivative and (S,S)‐cyclohexane‐1,2‐diamine. This polymeric compound was demonstrated to possess a cyclic structure with two to five repetitive units. The addition of chromium(II) salts led to the generation of a chiral catalyst that could be recovered as an insoluble powder. The performance of this new calixsalen‐type catalyst was examined in various transformations, particularly in its ability to promote nucleophilic epoxide ring opening under heterogeneous conditions. The target products were obtained in high yields and with improved selectivity compared with those obtained by using analogous linear polymers. The arrangement of the catalytic sites in the cyclic structure is probably more suitable for the necessary cooperative bimetallic pathway of this demanding reaction. The catalyst could be successfully recycled. This approach represents the first use of calixsalen complexes under heterogeneous catalytic conditions.     

Development of Asymmetric Reactions Catalyzed by Chiral Organotin‐Alkoxide Reagents

Asymmetric catalysis under almost‐neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)‐BINOL‐derived chiral tin‐dibromide reagent that possesses a bulky aryl group at the 3 or 3′ position as the chiral pre‐catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three‐component Mannich‐type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N‐nitroso aldol reaction of unsaturated lactones with nitrosoarenes.     

Selective response of antigen‐antibody reactions on chiral surfaces modified with 1,2‐diphenylethylenediamine enantiomers

This work reported a comparative analysis of the amperometric responses of antigen‐antibody reactions on two stable chiral surfaces which were modified with 1,2‐diphenylethylenediamine enantiomers. Alpha‐fetoprotein antibody and antigen (anti‐AFP and AFP) were selected as model systems. First, (1R,2R)‐1,2‐diphenylethylenediamine or (1S,2S)‐1,2‐diphenylethylenediamine was modified on the gold surface of the electrode through amide linkage to construct chiral surfaces. Then, anti‐AFP was immobilized on the chiral electrode surface by electrostatic and hydrogen bonding interactions. The electrochemical characteristics of the modified electrodes were studied via cyclic voltammetry. The selective current responses of antigen‐antibody reactions on chiral electrode surfaces for different incubation time and varying AFP concentrations were monitored. The antigen‐antibody reactions were greatly influenced by the chirality of 1,2‐diphenylethylenediamine enantiomers, and the amperometric responses obtained from the (1S,2S)‐1,2‐diphenylethylenediamine modified electrode was obviously stronger than that from the (1R,2R)‐1,2‐diphenylethylenediamine modified electrode. Such work may not only offer valuable reference to the research of chiral drugs, but also help to comprehend the high selectivity of chiral molecular species in biosystems. Copyright © 2011 John Wiley & Sons, Ltd.     

Influence of a Change in Helical Twisting Power of Photoresponsive Chiral Dopants on Rotational Manipulation of Micro‐Objects on the Surface of Chiral Nematic Liquid Crystalline Films

Herein we report a group of five planar chiral molecules as photon‐mode chiral switches for the reversible control of the self‐assembled superstructures of doped chiral nematic liquid crystals. The chiral switches are composed of an asymmetrically substituted aromatic moiety and a photoisomerizing azobenzene unit connected in a cyclic manner through methylene spacers of varying lengths. All the molecules show conformational restriction in the rotation of the asymmetrically substituted aromatic moiety in both the E and Z states of the azobenzene units resulting in planar chirality with separable enantiomers. Our newly synthesized compounds in pure enantiomeric form show high helical twisting power (HTP) in addition to an improved change in HTP between the E and Z states. The molecule with a diphenylnaphthalene unit shows the highest ever known initial helical twisting power among chiral dopants with planar chirality. In addition to the reversible tuning of reflection colors, we employed the enantiomers of these five compounds in combination with four nematic liquid crystalline hosts to study their properties as molecular machines; the change in HTP of the chiral dopant upon photoisomerization induces rotation of the texture of the liquid crystal surfaces. Importantly, this study has revealed a linear dependence of the ratio of the difference between HTPs before and after irradiation against the absolute value of the initial HTP, not the absolute value of the change in helical twisting power between two states, on the angle of rotation of micro‐objects on chiral nematic liquid crystalline films. This study has also revealed that a change in irradiation intensity does not affect the maximum angle of rotation, but it does affect the speed of rotational reorganization of the cholesteric helix.     

Copper‐Catalyzed Stereoselective Aminoboration of Bicyclic Alkenes

A copper‐catalyzed aminoboration of bicyclic alkenes, including oxa‐ and azabenzonorbornadienes, has been developed. With this method, amine and boron moieties are simultaneously introduced at an olefin with exo selectivity. Subsequent stereospecific transformations of the boryl group can provide oxygen‐ and nitrogen‐rich cyclic molecules with motifs that may be found in natural products or pharmaceutically active compounds. Moreover, a catalytic asymmetric variant of this transformation was realized by using a copper complex with a chiral bisphosphine ligand, namely (R,R)‐Ph‐BPE.     

Asymmetric Photochemical Synthesis of Chiral 5‐(R)‐(l)‐Menthyloxy‐4‐Cycloaminobutyrolactones

Through photocatalysed regiospecific and stereoselective additions of cycloamines to 5‐(R)‐(l)‐menthyloxy‐2 (5H)‐furanone (3), chiral 5‐(R)‐(l)‐menthyloxy‐4‐cycloaminobutyrolactones were synthesized. In the new asymmetric photoaddition of compound 3, the N‐methyl cyclic amines (4) gave novel chiral C? C photoadducts (5) in 24–50% isolated yields with d. e. ≥ 98%. However, the secondary cyclic amines (6) afforded optically active N? C photoadducts (7) in 34–58% isolated yields with d. e. ≥ 98% under the same condition. All the synthesized optically active compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]₅₈₉²⁰, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The photosynthesis of chiral butyrolactones and its mechanism were discussed in detail.     

Simple and efficient cleavage reaction of the boc group in heterocyclic compounds

Dedicated to the memory of Pr. Ladjama Daif A series of chiral cyclosulfamides have been synthesized by alkaline cyclisation starting from N‐benzoylamino acids (Ala, Val, Leu, Phe) derivatives and chlorosulfonyl isocyanate. A simplified and regioselective deprotection of the cyclic compounds (cyclosulfamides) containing the tert‐butyloxycarbonyl group (Boc) has been achieved in good yield by fusion under reduced pressure.     

Catalytic Enantioselective Aza‐Reformatsky Reaction with Cyclic Imines

A catalytic highly enantioselective aza‐Reformatsky reaction with cyclic aldimines and ketimines for the synthesis of chiral β‐amino esters with good yields and excellent enantioselectivities is reported. A readily available diaryl prolinol is used as a chiral ligand, ZnMe₂ as a zinc source and ethyl iodoacetate as reagent in the presence of air atmosphere. The reaction with cyclic ketimines generates a quaternary stereocenter with excellent levels of enantioselectivity. Furthermore, five‐membered N‐sulfonyl ketimines were used as electrophiles with good enantiomeric excesses, under the optimized reaction conditions. Moreover, several chemical transformations were performed with the chiral β‐amino esters.     

Approach to Fully Substituted Cyclic Nitrones from N‐Hydroxylactam Derivatives: Development and Application to the Total Synthesis of Cylindricine C

An approach to cyclic nitrones from N‐hydroxylactam derivatives is documented. The nucleophilic addition of an organolithium reagent to an N‐OSEM [SEM=2‐(trimethylsilyl)ethoxymethyl] lactam forms a five‐membered chelated intermediate, which undergoes both elimination and deprotection to give a fully substituted nitrone in a one‐pot process. When combined with the N‐oxidation of easily available chiral lactams, this method becomes especially useful for the quick synthesis of chiral nitrones in enantio‐pure form, enabling the concise total synthesis of cylindricine C.