•The first fluorescent probe having [2.2]paracyclophanyl group have been synthesized.•The probe 4a exhibits a highly selective and sensitive response to Hg2+.•The probe 4a has good biocompatibility in A549 cells.•The probe 4a can be applied to detect intracellular Hg2+ in A549 cells.•The crystal structure and spectral properties of 4b are investigated.For a better insight into the spectroscopic properties of [2.2]paracyclophane in fluorescent probes, a novel rhodamine-based chemodosimeter bearing [2.2]paracyclophane 4a has been designed and synthesized. The probe 4a exhibits a highly selective and sensitive response to Hg2+ over other transition metal ions in aqueous solution. Its detection limit is determined to be 77 nM. The significant changes in the fluorescence color could be used for the naked-eye detection. Furthermore, the probe 4a shows good membrane permeability and can be applied to detect intracellular Hg2+ in human lung adenocarcinoma cells (A549 cells). The crystal structure and spectral properties of its congener 4b that contains one 12-bromo [2.2]paracyclophane group and rhodamine moiety are also investigated for a comparison.

The first example of transition metal-free enantioselective 1,2-silylation of aromatic aldehydes is reported. This protocol enables an easy access to chiral α-hydroxysilanes from readily available aromatic aldehydes.

A series of novel oxazoline-substituted imidazolium salts with planar and central chirality has been successfully synthesized and applied to copper-catalyzed enantioselective 1,2-silylation of N-tosylaldimines. The oxazoline–carbene copper complex generated in situ by the reaction of the oxazoline-substituted imidazolium and Cu2O demonstrated an exceptionally high catalytic activity in the asymmetric 1,2-silylation of N-tosylaldimines, affording chiral α-amino silanes with excellent yields and enantioselectivities.Download high-res image (111KB)Download full-size image

A copper(I)-catalyzed tandem CuAAC/alkynylation reaction of various alkynes, organic azides, and bromoalkynes to provide rapid access to 5-alkynyl-1,2,3-triazoles has been developed. The reaction proceeded via a copper-catalyzed alkyne azide cycloaddition followed by interception of the in situ formed cuprate–triazole intermediate with bromoalkyne. This reaction offers a new method to afford fully substituted triazoles in high yields with complete regioselectivity under mild reaction conditions.

A series of planar chiral carbene–copper complexes based on the [2.2]paracyclophane backbone with a pseudo-ortho substitution pattern have been synthesized and applied to asymmetric β-boration of α,β-unsaturated esters. As a result, transannular electronic effects of the substituent of the chiral catalyst have significant influence on the catalytic performance. A variety of chiral β-hydroxyl esters were obtained in excellent enantioselectivities (up to 97% ee) and yields (up to 99%).

An enantioselective conjugate addition of boron to α,β-unsaturated ketones catalysed by either a N-heterocyclic carbene or a copper–carbene complex generated in situ from a new chiral bicyclic triazolium based on [2.2]paracyclophane is presented. The dual chiral carbene–copper catalyst has significant advantages over its carbene counterpart as an organocatalyst in asymmetric β-boration of acyclic enones, giving a variety of chiral β-boryl ketones in good yields and enantioselectivities. This is a successful example of employing the same N-heterocyclic carbene in one catalytic reaction as both an organocatalyst and a ligand for transition metal catalysis.

A series of new oxazoline-substituted imidazolium salts based on [2.2]paracyclophane were synthesized and characterized. The new bidentate oxazoline–carbene precursor with planar and central chirality had significant advantage than the bicyclic 1,2,4-triazolium salt derived from [2.2]paracyclophane as a monodentate carbene ligand in Cu(I)-catalyzed asymmetric β-boration of α,β-unsaturated esters, giving the desired products in high enantioselectivities and yields.

A successful development had been achieved in the asymmetric 1,2-addition of arylboronic acids to aromatic aldehydes by the use of macrocyclic planar chiral NHC–Rh complexes derived from [2.2]paracyclophane. A variety of chiral diarylmethanols were obtained in excellent yields and with moderate enantioselectivities.1,7-Bis[(Sp)-(+)-12-bromo-[2.2]paracyclophan-4-yl]-1,4,7-trioxaheptaneC36H36Br2O3[α]D20 = +58.8 (c 0.40, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)1,10-Bis[(Sp)-(+)-12-bromo-[2.2]paracyclophan-4-yl]-1,4,7,10-tetraoxadecaneC38H40Br2O4[α]D20 = +113.0 (c 0.20, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)1,16-Bis[(Sp)-(+)-12-bromo-[2.2]paracyclophan-4-yl]-1,4,7,10,13,16-hexaoxahexadecaneC42H48Br2O6[α]D20 = +33.3 (c 0.70, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)1,7-Bis[(Sp)-(+)-12-amino-[2.2]paracyclophan-4-yl]-1,4,7-trioxaheptaneC36H40N2O3[α]D20 = −129.8 (c 0.50, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)1,10-Bis[(Sp)-(+)-12-amino-[2.2]paracyclophan-4-yl]-1,4,7,10-tetraoxadecaneC38H44N2O4[α]D20 = −30.1 (c 0.03, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)1,16-Bis[(Sp)-(+)-12-amino-[2.2]paracyclophan-4-yl]-1,4,7,10,13,16-hexaoxahexadecaneC42H52N2O6[α]D20 = −55.3 (c 0.60, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-[(Sp)-(−)-12,12′-(1,4,7-Trioxaheptane-1,7-diyl)-4,4′-bis[2.2]paracyclophanyl]glyoxal diimineC38H38N2O3[α]D20 = −1570.0 (c 0.06, CH2Cl2)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-[(Sp)-(−)-12,12′-(1,4,7,10-Tetraoxadecane-1,10-diyl)-4,4′-bis[2.2]paracyclophanyl]glyoxal diimineC40H42N2O4[α]D20 = −1240.0 (c 0.06, CH2Cl2)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-[(Sp)-(−)-12,12′-(1,4,7,10,13,16-Hexaoxahexadecane-1,16-diyl)-4,4′-bis[2.2]paracyclophanyl]glyoxal diimineC50H44F3N2O5S[α]D20 = −500.0 (c 0.30, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-[(Sp)-(−)-12,12′-(1,4,7-Trioxaheptane-1,7-diyl)-4,4′-bis[2.2]paracyclophanyl]imidazolium triflateC40H39F3N2O6S[α]D20 = −89.5 (c 0.20, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-[(Sp)-(−)-12,12′-(1,4,7,10-Tetraoxadecane-1,10-diyl)-4,4′-bis[2.2]paracyclophanyl]imidazolium triflateC42H43F3N2O7S[α]D20 = −14.9 (c 0.02, CH2Cl2)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-[(Sp)-(−)-12,12′-(1,4,7,10,13,16-Hexaoxahexadecane-1,16-diyl)-4,4′-bis[2.2]paracyclophanyl]imidazolium triflateC46H51F3N2O9S[α]D20 = −70.0 (c 0.20, CH2Cl2)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)Chloro{N,N′-[(Sp)-(−)-12,12′-(1,4,7-trioxaheptane-1,7-diyl)-4,4′-bis[2.2]paracyclophanyl]imidazol-2-ylidene}silverC39H39AgClN2O3[α]D20 = −238.3 (c 0.18, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)Chloro{N,N′-[(Sp)-(−)-12,12′-(1,4,7,10-tetraoxadecane-1,10-diyl)-4,4′-bis[2.2]paracyclophanyl]imidazol-2-ylidene}silverC41H43AgClN2O4[α]D20 = −275.0 (c 0.30, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)Chloro{N,N′-[(Sp)-(−)-12,12′-(1,4,7,10,13,16-hexaoxahexadecane-1,16-diyl)-4,4′-bis[2.2]paracyclophanyl]imidazol-2-ylidene}silverC45H51AgClN2O6[α]D20 = −304.0 (c 0.25, CHCl3)Source of chirality: (Sp)-4-bromo-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Sp)

•Eight new p-terphenyls derivatives were successfully synthesized.•Compound 1 induced cell-cycle arrest and apoptosis in MDA-MB-435 cells.•Compound 1 is shown to interfere with topoisomerase reactions.A novel series of p-terphenyl derivatives (1–4, 1a–4a) was successfully synthesized and their in vitro anticancer activities were evaluated. Compound 1, showing the best antiproliferative activity with IC50 < 1 μM against MDA-MB-435 cells, was further investigated. Compound 1 brought about a remarkable accumulation of MDA-MB-435 cells in G2/M phase prior to the induction of apoptosis. Further antitumor mechanism study indicated that compound 1, which inhibited the enzyme activity of Topo I and Topo IIα by interfering predominantly with the enzyme, could be topoisomerase suppressors instead of poisons. We conclude that compound 1 represents a novel class of Topo catalytic suppressors for developing new chemotherapeutic agents.Compound 1 induced cell-cycle arrest and apoptosis in MDA-MB-435 cells.

A new planar and centrally chiral bicyclic 1,2,4-triazolium salt has been synthesized from [2.2]paracyclophane and phenylglycinol. The N-heterocyclic carbene (NHC) copper(I) complex generated in situ by the reaction of the triazolium salt and Cu2O was an efficient catalyst for the asymmetric β-boration of acyclic enones, producing β-boryl ketones in high yields and enantioselectivities.

Three novel planar chiral N-heterocyclic carbene silver and rhodium complexes based on [2.2]paracyclophane have been prepared. These could be used as catalysts/precatalysts for the asymmetric 1,2-addition of organoboronic acids to aldehydes. We optimized the reaction conditions and have applied ultrasonic irradiation in the asymmetric arylation for the first time. Under ultrasound irradiation, the combination of planar chiral NHC–Ag complex 5 and RhCl3 can achieve higher catalytic activities in the asymmetric addition of organoboronic acids to aldehydes.Chloro[N,N′-bis[(Rp)-(+)-4-[2.2]paracyclophanyl]imidazol-2-ylidene]silverC35H33AgClN2[α]D20=+73.3 (c 0.21, CH2Cl2)Source of chirality: N,N′-bis[(Rp)-(−)-4-[2.2]paracyclophanyl] imidazolium triflateAbsolute configuration: (Rp)Chloro(η2,η2-1,5-cyclo-octadiene)-[N,N′-bis[(Rp)-(+)-4-[2.2]paracyclophanyl]imidazole-2-ylidene]rhodiumC43H44ClN2Rh[α]D20=+47 (c 0.2, CH2Cl2)Source of chirality: N,N′-bis[(Rp)-(−)-4-[2.2]paracyclophanyl] imidazolium triflateAbsolute configuration: (Rp)Bromo[N,N′-bis[(Rp)-(+)-12-methoxy-4-[2.2]paracyclophanyl] imidazol-2-ylidene]silverC37H36AgBrN2O2[α]D20=+125.2 (c 0.27, CH2Cl2)Source of chirality: N,N′-bis[(Rp)-(−)-12-methoxy-4-[2.2]paracyclophanyl]imidazolium triflateAbsolute configuration: (Rp)

Several novel [2.2]paracyclophane-based amino thioureas have been designed and synthesized. The [2.2]paracyclophane-based amino thioureas were used as bifunctional catalysts for organocatalytic enantioselective aldol reactions between ketones and isatins, affording the desired adducts containing a chiral tertiary alcohol in high yields (up to 92% yield) and with good enantioselectivity (up to 88% ee). This is a successful example of employing planar chiral [2.2]paracyclophane-based amino thioureas in asymmetric aldol reactions.(RP,RP)-Bis(12-(3,5-bis(trifluoromethyl)phenyl thiocarboxamino)[2.2]paracyclophan-4-yl methylene)amineC52H43F12N5S2[α]D20=-79 (c 0.07, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP,RP)(RP,S)-4-(3,5-Bis(trifluoromethyl)phenyl thiocarboxamino)-12-prolinamido[2.2]paracyclophaneC30H28F6N4OS[α]D20=-146 (c 0.08, CH2Cl2)Source of chirality: (S)-proline; (RP)-4-amino-12-benzhydryldeneamino[2.2]paracyclophaneAbsolute configuration: (S,RP)(SP,S)-4-(3,5-Bis(trifluoromethyl)phenyl thiocarboxamino)-12-prolinamido[2.2]paracyclophaneC30H28F6N4OS[α]D20=+86 (c 0.1, CH2Cl2)Source of chirality: (S)-proline; (SP)-4-amino-12-benzhydryldeneamino[2.2]paracyclophaneAbsolute configuration: (S,Sp)(RP)-4-Aminomethyl-12-bromo[2.2]paracyclophaneC17H19BrN[α]D20=-165 (c 0.1, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP)(RP,RP)-Bis(12-bromo[2.2]paracyclophan-4-yl methylene)amineC34H34Br2N[α]D20=-91 (c 0.05, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP)(RP,RP)-Bis(12-amino[2.2]paracyclophan-4-yl methylene)amineC34H38N3[α]D20=-102 (c 0.1, CH2Cl2)Source of chirality: (RP)-4,12-dibromo[2.2]paracyclophaneAbsolute configuration: (RP)(RP,S)-4-Amino-12-(N-Boc-prolinamido)[2.2]paracyclophaneC26H34N3O3[α]D20=-248 (c 0.09, CH2Cl2)Source of chirality: (S)-proline; (RP)-4-amino-12-benzhydryldeneamino[2.2]paracyclophaneAbsolute configuration: (S,RP)

An efficient copper-catalyzed asymmetric conjugate boration has been achieved by exploiting a new planar and central chiral bicyclic triazolium ligand. This protocol was highly efficient and gave a variety of chiral secondary alkylboronates in 97–99% ee. A preliminary mechanistic study supports the bifunctional nature of the catalyst.

Dediazoniation reactions of (Sp)-4-bromo-13-[2.2]paracyclophanyldiazonium fluoborate 2a through a heterolytic cleavage process gave products with partial racemization. In contrast, dediazoniation reactions of (Sp)-2a undergoing a nonheterolytic cleavage process afforded products with retention of configuration. A key intermediate, the bromonium cation B, caused the racemization. The unexpected racemization allowed the mechanisms of the dediazoniation reaction to be probed.

A series of diastereomerically pure Schiff base ligands based on [2.2]paracyclophane backbones were synthesized and separated. The new planar chiral [2.2]paracyclophane Schiff bases were used as ligands in Cu-catalyzed asymmetric Henry reactions with high yields and enantioselectivities.(Sp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-fluoro-[2.2]paracyclophaneC24H30FNO2[α]D20=+655.0 (c 0.10, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Sp,S)(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-fluoro-[2.2]paracyclophaneC24H30FNO2[α]D20=-280 (c 0.10, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)(Sp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-iodo-[2.2]paracyclophaneC24H30INO2[α]D20=+756.0 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Sp,S)(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-iodo-[2.2]paracyclophaneC24H30INO2[α]D20=-431.8 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)(Sp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-methoxy-[2.2]paracyclophaneC25H33NO3[α]D20=+964.0 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Sp,S)(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-methoxy-[2.2]paracyclophaneC25H33NO3[α]D20=-613.1 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)(Rp,S)-5-(1-(1-Hydroxy-3,3-dimethylbutan-2-ylimino)ethyl)-4-hydroxy-13-(2,3-dimethoxyphenyl)-[2.2]paracyclophaneC32H39NO4[α]D20=+434.1 (c 0.1, CH2Cl2)Source of chirality: (S)-tert-leucinolAbsolute configuration: (Rp,S)

A series of novel planar chiral alkoxy/sulfonate-substituted carbene precursors have been designed and synthesized. They were used as N-heterocyclic carbene ligands in the Rh-catalyzed asymmetric addition of arylboronic acids to aromatic aldehydes, affording chiral diarylmethanols with high yields and moderate enantioselectivities.N,N′-Bis[(Sp)-(+)-12-methoxy-4-[2.2]paracyclophanyl]imidazolium triflateC38H37F3N2O5S[α]D20=+20.9 (c 0.36, CH2Cl2)Source of chirality: (Sp)-4-Amino-12-methoxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(−)-12-isopropoxy-4-[2.2]paracyclophanyl]imidazolium triflateC42H45F3N2O5S[α]D20=-74.4 (c 0.68, CH2Cl2)Source of chirality: (Sp)-4-Amino-12-i-propoxy [2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(+)-12-trifluoromethanesulfonyloxy-4-[2.2]paracyclophanyl]imidazolium triflateC38H31F9N2O9S3[α]D20=+146.3 (c 0.36, CH2Cl2)Source of chirality: (Sp)-4-Amino-12-trifluoromethanesulfonyloxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Rp)-(+)-12-methanesulfonyloxy-4-[2.2]paracyclophanyl]imidazolium bromideC37H37BrN2O6S2[α]D20=+82.6 (c 0.2, CH3CN)Source of chirality: (Rp)-4-Benzhydrylideneamino-12-hydroxy[2.2]paracyclophaneAbsolute configuration: (Rp)N,N′-Bis[(Sp)-(+)-13-methoxy-4-[2.2]paracyclophanyl]imidazolium triflateC38H37F3N2O5S[α]D20=+81.7 (c 0.17, CH2Cl2)Source of chirality: (Sp)-4-Amino-13-methoxy[2.2]paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(-)-12-methoxy-4-[2.2]paracyclophanyl]imidazolinium tetrafluoroborateC37H39BF4N2O2[α]D20=-58.8 (c 0.4, CH2Cl2)Source of chirality: (Sp)-4-Amino-12-methoxy[2.2]paracyclophaneAbsolute configuration: (Sp)

Novel helical macrocyclic imines derived from planar chiral [2.2]paracyclophane were synthesized. The chiroptical properties of the enantiopure compounds were investigated and their absolute configurations were assigned.

Novel planar chiral pseudo-geminal and pseudo-ortho-oxazoline substituted [2.2]paracyclophanyl imidazo[1,5-a]pyridinium triflates were synthesized. During the synthesis of a pseudo-ortho imidazo[1,5-a]pyridinium triflate based on [2.2]paracyclophane, the diastereoisomers of 4-amino-12-oxazolinyl[2.2]paracyclophane were separated. The imidazo[1,5-a]pyridinium triflates were used as carbene precursors in Cu-catalyzed enantioselective conjugate β-borylation of enones. In preliminary tests of a series of ligands and substrates, we obtained up to 84% enantioselectivity.(R,4Rp,13Sp)-3-{13-(4-Phenyloxazolin-2-yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflateC33H27F3N3O4S[α]D20=+43.9 (c 0.2, CH2Cl2)Source of chirality: (R,4Rp,13Sp)-4-bromo-13-(4-phenyloxazolin-2-yl)[2.2]paracyclophaneAbsolute configuration: (R,4Rp,13Sp)(R,4Sp,13Rp)-3-{13-(4-Phenyloxazolin-2-yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflateC33H27F3N3O4S[α]D20=+16.7 (c 0.3, CH2Cl2)Source of chirality: (R,4Sp,13Rp)-4-bromo-13-(4-phenyloxazolin-2-yl)[2.2]paracyclophaneAbsolute configuration: (R,4Sp,13Rp)(R,Rp)-3-{12-(4-Phenyloxazolin-2-yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflateC33H27F3N3O4S[α]D20=+187.5 (c 0.2, CH2Cl2)Source of chirality: (R,Rp)-4-benzhydrylideneamino-12-(4-phenyl oxazolin-2-yl)[2.2]paracyclophaneAbsolute configuration: (R,Rp)(R,Sp)-3-{12-(4-Phenyloxazolin-2-yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflateC33H27F3N3O4S[α]D20=-122.4 (c 0.2, CH2Cl2)Source of chirality: (R,Sp)-4-benzhydrylideneamino-12-(4-phenyl oxazolin-2-yl)[2.2]paracyclophaneAbsolute configuration: (R,Sp)(S,Sp)-3-{12-(4-t-Butyloxazolin-2-yl)[2.2]paracyclophane-4-yl}imidazo[1,5-a]pyridinium triflateC31H31F3N3O4S[α]D20=-235.7 (c 0.2, CH2Cl2)Source of chirality: (S,Sp)-4-bromo-12-(4-t-butyloxazolin-2-yl)[2.2]paracyclophaneAbsolute configuration: (S,Sp)

A series of new planar and central chiral ligands based on [2.2]paracyclophane backbones were designed and prepared from enantiomerically pure 4-amino-13-bromo[2.2]paracyclophane and commercially available chiral amino alcohols. Their application in a copper-catalyzed asymmetric Henry reaction resulted in secondary alcohols with high yield and excellent selectivity for active aldehydes (up to 94% ee). This is a successful example of employing planar chiral [2.2]paracyclophane ligands in copper-catalyzed reaction.Schiff base of (4Sp,5Rp,13Rp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and benzylamineC25H24BrNO[α]D20=-19.6 (c 0.40, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (4Sp,5Rp,13Rp)Schiff base of (4Sp,5Rp,13Rp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (R)-2-phenylglycinolC26H26BrNO2[α]D20=-195.1 (c 0.50, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (R,4Sp,5Rp,13Rp)Schiff base of (4Sp,5Rp,13Rp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (S)-tert-leucinolC24H30BrNO2[α]D20=-415.5 (c 0.20, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (S,4Sp,5Rp,13Rp)Schiff base of (4Sp,5Rp,13Rp)-5-benzoyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (R)-2-phenylglycinolC31H28BrNO2[α]D20=-265.5 (c 0.20, CH2Cl2)Source of chirality: (4Sp,13Rp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (R,4Sp,5Rp,13Rp)Schiff base of (4Rp,5Sp,13Sp)-5-acetyl-13-bromo-4-hydroxy-[2.2]paracyclophane and (S)-tert-leucinolC24H30BrNO2[α]D20=+817.8 (c 0.20, CH2Cl2)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (S,4Rp,5Sp,13Sp)Schiff base of (4Rp,5Sp,13Sp)-5-acetyl-4-hydroxy-13-(3-meth-oxylphenyl)[2.2]paracyclophane and (S)-tert-leucinolC31H37NO3[α]D20=+567.5 (c 0.20, CH2Cl2)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]-paracyclophaneAbsolute configuration: (S,4Rp,5Sp,13Sp)

A series of planar chiral imidazolium salts derived from [2.2]paracyclophane have been synthesized and characterized. By using these imidazolium salts as carbene precursors, the Rh-catalyzed 1,2-addition of arylboronic acids to aldehydes proceeded readily with low catalyst loadings (0.03–0.3 mol %) and gave a variety of chiral diarylmethanols in excellent yields and moderate enantioselectivities.N,N′-Bis[(Sp)-(+)-12-bromo-4-[2.2]paracyclophanyl]imidazolium chlorideC35H31Br2ClN2[α]D20=+26.7 (c 0.50, CHCl3)Source of chirality: (Sp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Sp)N,N′-bis[(Sp)-(+)-12-bromo-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC36H31Br2F3N2O3S[α]D20=+18 (c 1.3, CHCl3)Source of chirality: (Sp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(+)-12-(2-methoxyphenyl)-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC50H44F3N2O5S[α]D20=+83.2 (c 0.50, CHCl3)Source of chirality: (Sp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(+)-12-phenyl-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC48H40F3N2O3S[α]D20=+64.7 (c 0.50, CHCl3)Source of chirality: (Sp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(+)-12-(3-methoxyphenyl)-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC50H44F3N2O5S[α]D20=+78.5 (c 0.50, CHCl3)Source of chirality: (Sp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[(Sp)-(+)-12-(1-Naphthyl)-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC56H44F3N2O3S[α]D20=+121.3 (c 0.50, CHCl3)Source of chirality: (Sp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Sp)N,N′-Bis[((4Rp,13Sp)-13-bromo-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC36H31Br2F3N2O3S[α]D20=+151.0 (c 0.50, CHCl3)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]paracyclophaneAbsolute configuration: (4Rp,13Sp)N,N′-Bis[(4Rp,13Sp)-13-phenyl-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC48H40F3N2O3S[α]D20=+172.8 (c 0.50, CHCl3)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]paracyclophaneAbsolute configuration: (4Rp,13Sp)N,N′-Bis[(4Rp,13Sp)-13-(3-methoxyphenyl)-4-[2.2]paracyclophanyl]imidazolium trifluoromethanesulfonateC50H44F3N2O5S[α]D20=+210.3 (c 0.50, CHCl3)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]paracyclophaneAbsolute configuration: (4Rp,13Sp)N,N′-Bis[(Rp)-(−)-4-[2.2]paracyclophanyl]imidazoliumTrifluoromethanesulfonateC36H33F3N2O3S[α]D20=-26.4 (c 0.50, CHCl3)Source of chirality: (4Rp,13Sp)-4-amino-13-bromo[2.2]paracyclophaneAbsolute configuration: (Rp)N,N′-Bis[(Rp)-(−)-12-bromo-4-[2.2]paracyclophanyl]imidazolinium TetrafluoroborateC35H33BBr2F4N2[α]D20=-52.0 (c 0.12, CHCl3)Source of chirality: (Rp)-4-amino-12-bromo[2.2] paracyclophaneAbsolute configuration: (Rp)

The macrocyclic bisbibenzyl dihydroptychantol A (DHA), previously isolated from Asterella angusta, was synthesized and showed significant multidrug resistance (MDR) reverting activity in chemoresistant cancer cells. In an attempt to discover more potent MDR reversal agents for efficient cancer chemotherapy, DHA derivatives with thiazole rings (19–22) were synthesized, and their cytotoxicities and MDR reversal activities were evaluated in adriamycin-resistant K562/A02, vincristine-resistant KB/VCR and in their parental cells by MTT assays. In response to treatment with each compound, the K562 cell line was the most sensitive, and the vincristine-resistant KB/VCR cell line was the most resistant. Marked decreases in K562 and K562/A02 cell viability were detectable after treatment with the synthesized derivatives of DHA, while less inhibitory effects on cell growth were observed in chemical-resistant KB/VCR and KB cells. Moreover, among the tested compounds, the intermediate 17 and the analogues 19, 20, and 21 showed potent MDR reversal activities and increased vincristine cytotoxicity in KB/VCR cells, with the reversal fold ranges from 10.54 to 13.81 (10 μM), which is 3.2–4.3-fold stronger than the natural product DHA.

An enantioselective conjugate addition of boron to α,β-unsaturated ketones catalysed by either a N-heterocyclic carbene or a copper–carbene complex generated in situ from a new chiral bicyclic triazolium based on [2.2]paracyclophane is presented. The dual chiral carbene–copper catalyst has significant advantages over its carbene counterpart as an organocatalyst in asymmetric β-boration of acyclic enones, giving a variety of chiral β-boryl ketones in good yields and enantioselectivities. This is a successful example of employing the same N-heterocyclic carbene in one catalytic reaction as both an organocatalyst and a ligand for transition metal catalysis.

The first example of transition metal-free enantioselective 1,2-silylation of aromatic aldehydes is reported. This protocol enables an easy access to chiral α-hydroxysilanes from readily available aromatic aldehydes.