Β-aryl Group Research Articles

House-Meinwald rearrangement of aryl-substituted epoxysulfones in hexafluoroisopropanol (HFIP)

β-Aryl-substituted α,β-epoxysulfones undergo House-Meinwald rearrangement to form α-aryl, α-sulfonyl aldehydes in high yields upon dissolution in hexafluoroisopropanol (HFIP), and in some cases, heating. These compounds are typically isolated as the corresponding alcohols following reduction with NaBH4. The β-aryl group is generally required for rearrangement and a variety of substitution patterns are tolerated. A one-pot rearrangement/reductive amination sequence transforming the phenyl-substituted epoxysulfone to the corresponding β-aminosulfone is also reported. The epoxysulfone rearrangement substrates are directly accessible via Darzens reactions of aldehydes with chloromethyl aryl sulfones, which are themselves available using one-pot transformations of sulfonyl chlorides or sulfinate salts.

Superacid-Mediated Intramolecular Cyclization/Condensation: Facile One-Pot Synthesis of Spirotetracyclic Indanones and ­Indenes

A facile, superacid-promoted, domino, one-pot synthesis of novel spirotetracyclic indanones through intramolecular Friedel–Crafts acylation/alkylation of α,β-unsaturated cinnamic acid esters is presented. Interestingly, when the β-aryl group contained electron-withdrawing substituents such as fluoro, chloro, or bromo, the reaction took a different mechanistic path and afforded arylindenes as the end products.

Comparison of electronic effects of β-aryl substituents on optical and electrochemical properties of 5,15-diazaporphyrin π-systems

The syntheses and optical/electrochemical properties of 3-aryl-10,20-dimesityl-5,15-diazaporphyrin-metal complexes (MDAPs; mesityl = 2,4,6-trimethylphenyl; M = Ni , Zn ) are reported. Treatment of 3-bromo-MDAPs with arylboronic acids in the presence of a Pd catalyst and a bulky phosphine ligand in a dioxane-water mixed solvent afforded the corresponding 3-aryl-MDAPs in moderate to good yields. X-ray crystallographic analysis of p- EtO 2 CC 6 H 4- NiDAP showed that the β-aryl group was tilted toward the NiDAP ring, with a dihedral angle of 21.7°. In the UV-visible absorption spectra, all the Ar-MDAPs showed intense Q-bands attributable to HOMO-to-LUMO transitions. The para substituents were found to influence the HOMO energies, which eventually resulted in fine tuning of the HOMO–LUMO gaps of the diazaporphyrin chromophores. It is worth noting that the p- Ph 2 NC 6 H 4- ZnDAP showed broad absorption and emission bands in the visible-near-infrared regions. The large Stokes shifts and their linear solvation energy relationships vs. orientation polarizability show that this Ph 2 N -substituted derivative has intrinsically high charge transfer from the triphenylamine (donor) to the ZnDAP (acceptor) unit. These experimental observations were supported by theoretical calculations for model Ar-ZnDAP compounds. These results confirm that the introduction of a highly electron-donating aryl group at the peripheral β-carbon is a promising strategy for enhancing the light-harvesting and light-emitting abilities of diazaporphyrin-based π-systems in the visible-near-infrared regions.

Elimination Reactions of Aryl Furylacetates Promoted by R2NH-R2NH2+in 70 mol% MeCN(aq). Effects of β-Aryl on the Ketene-Forming Transition-State

, the effect of the β-aryl group on the ketene-formingelimination was assessed.Key Words : Elimination, E2 and E1cb Mechanism, β–Aryl Group effectIntroductionExtensive studies of the structure-reactivity relationshipsin the ketene-forming elimination reactions have led to thequalitative understanding of the relationship between thereactant structure and the mechanism.

Eliminations from (E)-2,4-Dinitrobenzaldehyde O-Aryloximes Promoted by R3N in MeCN. Effects of β-Aryl Group and Base-Solvent on the Nitrile-Forming Transition-State

The transition state was shifted toward theE1cb corner by an electron-withdrawing β-aryl substituentand toward the E1 intermediate and the product by astronger base in the reaction coordinate diagram. On theother hand, when the leaving group was changed from 2,4-dinitrophenoxide to picrate, the ρ value decreased but the βvalue increased. The results are in conflict with the predic-tion of the reaction coordinate diagram because both ρ and βvalues should be decreased with a better leaving group. Theunusual changes in the transition-state structure noted withthe leaving group variation have been interpreted as result-ing from a large difference in the anion-stabilizing ability ofthe leaving groups. However, the validity of this interpreta-tion remains to be verified. To determine whether a change in mechanism could berealized by introducing an even more electron-withdrawingβ-aryl substituent, we have now studied the reactions of ( E)-2,4-dinitrobenzaldehyde O-aryloxime with R

Undecaphenylcorroles

A first major study of undecaphenylcorrole (UPC) derivatives is presented. Three different Cu-UPC derivatives with different para substituents X (X = CF(3), H, CH(3)) on the β-aryl groups were synthesized via Suzuki-Miyaura coupling of Cu[Br(8)TPC] and the appropriate arylboronic acid. A single-crystal X-ray structure of the X = CF(3) complex revealed a distinctly saddled macrocycle conformation with adjacent pyrrole rings tilted by ~60-66° relative to one another (within the dipyrromethane units), which is somewhat higher than that observed for β-unsubstituted Cu-TPC derivatives but slightly lower than that observed for Cu[Br(8)TPC] (~70°) derivatives. Electrochemical and electronic absorption measurements afforded some of the first comparative insights into meso versus β substituent effects on the copper corrole core. The Soret maxima of the Cu-UPC complexes (~440-445 nm), however, are comparable to those of Cu[Br(8)TPC] derivatives and are considerably red-shifted relative to Cu-TPC derivatives. Para substituents on the β-phenyl groups were found to tune the redox potentials of copper corroles more effectively than those on meso-phenyl substituents, a somewhat surprising observation given that neither the HOMO nor LUMO has significant amplitudes at the β-pyrrolic positions.

Low-Energy States of Manganese–Oxo Corrole and Corrolazine: Multiconfiguration Reference ab Initio Calculations

Manganese(V)-oxo corrole and corrolazine have been studied with ab initio multiconfiguration reference methods (CASPT2 and RASPT2) and large atomic natural orbital (ANO) basis sets. The calculations confirm the expected singlet d(δ)(2) ground states for both complexes and rule out excited states within 0.5 eV of the ground states. The lowest excited states are a pair of Mn(V) triplet states with d(δ)(1)d(π)(1) configurations 0.5-0.75 eV above the ground state. Manganese(IV)-oxo macrocycle radical states are much higher in energy, ≥1.0 eV relative to the ground state. The macrocyclic ligands in the ground states of the complexes are thus unambiguously 'innocent'. The approximate similarity of the spin state energetics of the corrole and corrolazine complexes suggests that the latter macrocycle on its own does not afford any special stabilization for the Mn(V)O center. The remarkable stability of an Mn(V)O octaarylcorrolazine thus appears to be ascribable to the steric protection afforded by the β-aryl groups.

Unsymmetrical Chiral PCN Pincer Palladium(II) and Nickel(II) Complexes with Aryl-Based Aminophosphine–Imidazoline Ligands: Synthesis via Aryl C–H Activation and Asymmetric Addition of Diarylphosphines to Enones

Chiral 3-(2′-imidazolinyl)anilines 3a–c were easily synthesized by converting the carboxyl and nitro groups in commercially available 3-nitrobenzoic acid to chiral imidazoline and amine, respectively. The one-pot phosphorylation/metalation reaction of 3-(2′-imidazolinyl)anilines 3a–c, where the amino group in 3a–c was first phosphorylated by reaction with PPh2Cl, followed by metalation with PdCl2 or anhydrous NiCl2 in situ, afforded the three unsymmetrical chiral PCN pincer Pd(II) complexes 4a–c and the Ni(II) complex 5a with aryl-based aminophosphine–imidazoline ligands via aryl C–H bond activation of the related ligands. All of the new compounds were characterized by elemental analysis (HRMS for ligand precursors), 1H and 13C NMR, 31P{1H} NMR (for pincer complexes), and IR spectra. The molecular structures of Pd complexes 4a,c and that of Ni complex 5a have been determined by X-ray single-crystal diffraction. Each complex adopts a typical distorted-square-planar geometry. The potential of the obtained chiral pincers in the asymmetric addition of diarylphosphines to β-substituted enones or trans-β-nitrostyrene was investigated. The Pd pincer 4c, the chirality of which originated from l-phenylglycinol, was found to be an effective catalyst for the asymmetric addition of diphenylphosphine to a series of β-aryl enones with high enantioselectivities (12 examples, 51–94% ee's). In particular, excellent yields and enantioselectivities (>90% yields and ≥90% ee's) were obtained when β-aryl groups in the enones bore an electron-withdrawing group such as p-NO2.

Elimination Reactions of (E)-2,4,6-Trinitrobenzaldehyde O-Aryloximes Promoted by R3N/R3NH+in 70 mol% MeCN(aq). Effect of β-Aryl Group the Nitrile-Forming Transition-State

Nitrile-forming eliminations from <TEX>$(E)-2,4,6-(NO_2)_3C_6H_2CH=NOC_6H_4-2-X-4-NO_2$</TEX> (1) promoted by <TEX>$R_3NH/R_3NH^+$</TEX> in 70 mol % MeCN(aq) have been studied kinetically. When X = <TEX>$NO_2$</TEX>, the reactions exhibited second-order kinetics as well as Br<TEX>$\"{o}$</TEX>nsted <TEX>${\beta}$</TEX> = 0.63 and <TEX>${\mid}{\beta}_{lg}{\mid}$</TEX> = 0.34-0.46, and an E2 mechanism is evident. As the leaving group was made poorer (X = H, Cl, and <TEX>$CF_3$</TEX>), Br<TEX>$\"{o}$</TEX>nsted <TEX>${\beta}$</TEX> value increased from 0.63 to 0.85-0.89 without much change in the <TEX>${\mid}{\beta}_{lg}{\mid}$</TEX> value E2, indicating that structure of the transition state changed to an E1cb-like with extensive <TEX>$C_{\beta}-H$</TEX> bond cleavage, significant negative charge development at the <TEX>${\beta}$</TEX>-carbon, and limited <TEX>$C_{\alpha}$</TEX>-OAr bond cleavage.

Elimination of nitrile from (E)-2,4,6-trinitrobenzaldehyde O-pivaloyloxime promoted by R2NH in MeCN. Effect of β-aryl group on the nitrile-forming transition-state

Nitrile-forming eliminations from (E)-2,4,6-(NO2)3C6H2CH=NOC(O)(CH3)3 promoted by R2NH in MeCN have been studied kinetically. The reactions are second-order and exhibit substantial Hammett ρ and Bronsted β values. The k 2 value for elimination from (E)-2,4,6-trinitrobenzaldehyde O-pivaloyloxime promoted by i-Pr2NH in MeCN falls on a single line in the Hammett plot for different β-aryl substituents, which have been shown to react by the E2 mechanism. This result indicated that the reaction mechanism is not changed by the introduction of the 2,4,6-trinitro substituents, and that the elimination reactions from (E)-benzaldehyde O-pivaloyloximes series proceed by the common E2 mechanism.

Base-promoted elimination reactions of (E)- and (Z)-arylaldehyde O-benzoyloximes. Effects of stereochemistry, β-aryl group and base-solvent on the nitrile-forming transition states

Base-promoted elimination reactions of (E)- and (Z)-arylaldehyde O-benzoyloximes. Effects of stereochemistry, β-aryl group and base-solvent on the nitrile-forming transition states

Elimination Reactions of (E)-2,4,6-Trinitrobenzaldehyde O-benzoyloximes Promoted by R2NH in MeCN. Change of Reaction Mechanism

A combination of a strong electron-withdrawing β-aryl group and anion-solvating protic solvent was required for the mecha-nistic change.We were interested in learning if a change to the E1cB mechanism could be realized in aprotic solvent by making the β-aryl group even more electron-withdrawing. To explore such possibility, we have now studied the reactions of (

Asymmetric epoxidation of substituted chalcones and chalcone analogues catalyzed by α- d-glucose- and α- d-mannose-based crown ethers

The chiral monoaza-15-crown-5 lariat ethers annellated to methyl-4,6- O-benzylidene-α- d-glucopyranoside- 1 or mannopyranoside 2 have been applied as phase-transfer catalysts in the epoxidation of substituted chalcones and chalcone analogues with tert-butylhydroperoxide resulting in significant asymmetric induction. It was found that the position of the substituents in the aromatic ring of the chalcone had an influence both on the chemical yields and enantiomeric excesses. The lowest enantioselectivities (62–83% ee) were found in the case of ortho-substituted model compounds. The highest ee values (ee of 83–97%) were obtained in the case of para-substituted models. From among the chalcone analogues, the maximum ee (90–92%) was detected for the model compound having α- tert-butyl- and β-aryl groups. Using glucose-based crown ether 1, formation of the (−)-enantiomer was preferred, while applying mannose-based 2 as the catalyst, the (+)-enantiomer was in excess.

Eliminations from aryl bis(p-chlorophenyl)acetates promoted by R2NH in MeCN. Effects of base-solvent and β-aryl group

Elimination reactions of (4′-ClC6H4)2CHCO2C6H3-2-X-4-NO2 promoted by R2NH in MeCN have been studied kinetically. The observed second-order kinetics, Bronsted β = 0.44–0.86 and |βblog| = 0.46–0.69 are consistent with the E2 mechanism. The Bronsted β decreased as the leaving group was made more nucleofugic and the |βlog| increased with a weaker base. Comparison with existing data reveals that the structure of the transition state is relatively insensitive to the base-solvent and β- aryl substituent on the E2 transition state.

Synthesis of β-ketophosphonates with electron rich β-aryl groups as useful organophosphorus reagents in lignans synthesis

Investigation of the oxidation reaction of electron rich alkoxy substituted β-aryl β-hydroxyphosphonates to corresponding β-ketophosphonates, which may be utilized in syntheses of lignans with various oxidizing agents (PCC, PDC, SIBX, CAN, Oxone ®, KMNO 4/SiO 2, KMnO 4/MS 4 Å, KMnO 4/CuSO 4, KMnO 4/CuSO 4/Al 2O 3, MnO 2, CrO 3/SiO 2, H 2O 2/salen) is described. The effect of oxidants and reaction conditions on the reaction efficiency and yield was also investigated.

Exalted Resonance Demands in the Substituent Effects on the Acetolyses of 2-Arylethyl Trifluoromethanesulfonates Destabilized by CN and CF3 Groups

Abstract Substituent effects on the acetolysis rates of 2-aryl-1-cyano-1-(trifluoromethyl)ethyl trifluoromethanesulfonates (α-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (β-OTf) were investigated by using LArSR equation. The obtained ρ and r+ values were ρ = −3.28, r+ = 0.98 and ρ = −3.48, r+ = 0.93 for the acetolysis of α-OTf and β-OTf, respectively. The obtained ρ values are comparable to those for typical aryl-assisted solvolyses, but the r+ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted solvolyses are assisted by the strong participation of the β-aryl group.

Asymmetric aza-Michael reactions of alpha,beta-unsaturated ketones with bifunctional organic catalysts.

Asymmetric aza-Michael reactions of alpha,beta-unsaturated ketones with bifunctional organic catalysts.

Ketene-Forming Elimination Reactions from Aryl Thienylacetates Promoted by R2NH in MeCN. Effects of Base-Solvent and β-Aryl Group

Ketene-forming eliminations from C4H3(S)CH2C(O)O-C6H3-2-X-4-NO2 (1) promoted by R2NH in MeCN have been studied kinetically. The reactions are second-order and exhibit Bronsted β =0.51-0.62 and |βlg|= 0.47-0.53. Hence, an E2 mechanism is evident. The Bronsted β increased from 0.33 to 0.53 and |βlg| remained nearly the same by the change of the base-solvent from Bz(i-Pr)NH/Bz(i-Pr)NH2+ in 70 mol% MeCN(aq) to Bz(i-Pr)NH-MeCN, indicating a change to a more symmetrical transition state with similar extents of Cβ -H and Cα -OAr bond cleavage. When the β-aryl group was changed from thienyl to phenyl in MeCN, the β value increased from 0.53 to 0.73 and |βlg| decreased from 0.53 to 0.43. This indicates that the transition state became skewed toward more Cβ -H bond breaking with less Cα-OAr bond cleavage. Noteworthy is the greater double bond stabilizing ability of the thienyl group in the ketene-forming transition state.

Elimination Reactions of N-Alkyl-N-chlorothenylamines Promoted by MeONa−MeOH and Et2NH−MeCN. Effect of the β-Aryl Group on the Imine-Forming Transition State

Elimination reactions of N-alkyl-N-chlorothenylamines 1-4 with MeONa-MeOH and Et(2)NH-MeCN have been studied kinetically. The elimination reactions are regiospecific, producing only the conjugated imines. The reactions are second order and exhibit substantial values of Hammett rho and k(H)/k(D), and an E2 mechanism is evident. The relative rates of elimination for Me/Et/i-Pr/t-Bu substituents are 1/0.5/0.2/0.02 with MeONa-MeOH and 1/0.4/0.2/0.06 with Et(2)NH-MeCN. The transition state structure changes toward more product-like as the base is changed from MeONa-MeOH to Et(2)NH-MeCN. Comparison with existing data reveals that the structure of the transition state is relatively insensitive to the beta-aryl group variation.

2,3-Disubstituted 6-azabicyclo[3.2.1]octanes as novel dopamine transporter inhibitors

A series of cis and trans 3β-aryl-2-carbomethoxy-6-azabicyclo[3.2.1]octanes, with different substitution at the para-position of the aryl group, were synthesized and examined for reuptake inhibition at the dopamine transporter (DAT). The potency for inhibition of DA reuptake was compared with that of cocaine to determine the significance of the replacement of the 8-azabicyclo[3.2.1]octane (tropane nucleus), displayed in cocaine, for the 6-azabicyclo[3.2.1]octane (normorphan framework). This bicyclic core structure constitutes a novel chemical scaffold in DAT inhibitor design, which may provide new insights into the 3D structure of the DAT and its interaction with cocaine and DA. Among these compounds, the trans-amine series 8 were the most potent ligands at the DAT. In particular, the normorphan analogue 8c (bearing a p-chloro substituent at the β-aryl group, IC 50=452 nM) displayed a potency that is in the same range as cocaine (IC 50=459 nM) itself.