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

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)

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)

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.

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.