Carlo Rosini

Cinchona alkaloids for preparing new, easily accessible chiral stationary phases.I. 11-(10,11-Dihydro-6′-methoxy-cinchonan-9-OL)-tiopropylsilanized silica.

Abstract By reaction of mercatopropylsilanized silica with quinine in the presence of AIBN as radical initiator, a silica supported alkaloid can be obtained, which is effective in the HPLC resolution of racemic arylalkylcarbinols and binaphtol derivatives.

Cinchona alkaloids for preparing new, easily accessible chiral stationary phases : II. Resolution of binaphthol derivatives on silica-supported quinine☆

Abstract The preparation of the new chiral stationary phase SiSQuin, obtained by reaction of γ-mercaptopropylsilanized silica with the commercially available Cinchona alkaloid quinine, is described. This support is efficient for the rapid (6–7 min) separation of some binaphthol derivatives (separation factors between 1.08 and 1.16). The use of a circular dichroism detector allows the elution order to be established in a non-empirical way. This information is then used to propose a chiral recognition mechanism.

Heterogeneous Catalytic Asymmetric Dihydroxylation of Olefins with the OsO4/Poly(9-O-Acylquinine-co-Acrylonitrile) System

Abstract Heterogeneous catalytic asymmetric dihydroxylation of olefins has been achieved using, as chiral ligands of OsO4, the title insoluble polymeric derivatives of quinine.

A novel application of cinchona alkaloids as chiral auxiliaries: preparation and use of a new family of chiral stationary phases for the chromatographic resolution of racemates

Abstract The preparation of new chiral stationary phases derived from quinine, quinidine and cinchonidine and their application to resolution of racemic binaphthyl derivatives are described. From the comparison of the results achieved on the three phases, the knowledge of the elution orders, obtained by circular dichroism, and the analysis, by 1H NMR spectroscopy, of the structures of the adducts between quinine and 2-(2-propoxy)- 1,1-binaphthyl-2-ol, it has been possible to provide an experimental basis to a chiral recognition mechanism.

Determination of absolute configuration using vibrational circular dichroism spectroscopy: the chiral sulfoxide 1-thiochroman S-oxide

We have determined the absolute configuration of the chiral sulfoxide 1-thiochroman S-oxide 1 using vibrational circular dichroism (VCD) spectroscopy. The VCD spectrum of a CCl4 solution of 1 was analyzed using density functional theory (DFT), which predicts three stable conformations of 1, separated by <1 kcal/mol. The VCD spectrum predicted using the DFT/GIAO methodology for the equilibrium mixture of the three conformations of (S)-1 is in excellent agreement with the experimental spectrum of (+)-1. The absolute configuration of 1 is therefore (R)-(−)/(S)-(+). (+)-1 and (−)-1 of high enantiomeric excess (e.e.) were synthesized in high yields via asymmetric oxidation of 1-thiochroman 2 using Ti(iso-PrO)4/(R,R)-1,2-diphenylethane-1,2-diol/H2O/tert-butyl hydroperoxide and Ti(iso-PrO)4/l-diethyl tartrate/H2O/cumene hydroperoxide, respectively.

Absolute configuration assignment of inherently chiral calix[4]arenes using DFT calculations of chiroptical properties.

The racemate of an inherently chiral meta-substituted calix[4]arene derivative 3 has been resolved via enantioselective HPLC. Measured optical rotation dispersion and electronic circular dichroism have been compared with DFT theoretical predictions. The comparison indicates that the absolute configuration of the dextrorotatory enantiomer (+)-3 is cS. The procedure has been successfully tested against a literature precedent confirming the validity of the method.

Preparation and resolution of chiral areneruthenium(II) complexes

Abstract The synthesis of the chiral complexes [RuCl 2 (η n6 -C 6 H 5 CHMeR) 2 ], (R = Et, 1 , t Bu, 2 ), is reported. 1 was prepared from RuCl 3 ·3H 2 O and 1-(2-butyl)- 1,4-cyclohexadiene, whereas 2 was obtained starting from [Ru(η 6 -naphthalene)(η 4 -COD)] (COD = 1,5-cyclooctadiene) and 2,2-dimethyl-3-phenylbutane, which gives [Ru(η 6 -C 6 H 5 CHMe t Bu)(η 4 -COD)] and subsequent reaction with HCl. Complexes 1 and 2 react with (+)-neomenthyldiphenylphosphine (NMDPP) to give monomeric diastereomers [RuCl 2 (η 6 -C 6 H 5 CHMeEt)(NMDPP)] ( 3a , 3b ), and [RuCl 2 (η 6 C 6 H 5 CHMe t Bu)(NMDPP)], ( 4a , 4b ), which were separated by HPLC. The structure of compound 3a was solved by Patterson and Fourier techniques and refined by full-matrix least-squares analysis to R = 0.053, R w = 0.061. The arene is η 6 -bonded to the ruthenium with the phosphorus and the two chlorine atoms arranged as a three legs piano stool. The absolute configuration of the chiral centre of the aromatic ligand in 3a is R . The monomeric diastereomers 3a , 3b , 4a and 4b , were reconverted into their dimeric precursors ( R,R )- 1a , ( S,S )- 1b , ( R,R )- 2a and ( S,S )- 2b as pure enantiomers. The CD spectra of ( R,R )- 1a and ( S,S )- 2b are also reported.

Absolute Configuration through the DFT Simulation of the Optical Rotation. Importance of the Correct Selection of the Input Geometry: A Caveat

In ab initio calculation of ORs of flexible molecules, the input geometries and conformer populations obtained at different levels of theory can yield opposite OR values. Therefore, when at the commonly used DFT/B3LYP/6-31G* level several conformers result, even showing the same sign of OR, additional geometry optimization at a higher level of theory will be absolutely required.

Chiral stationary phase derived from l-lactic acid for the optical resolution of N-(3,5-dinitrobenzoyl)amino acid methyl esters

Abstract A new chiral stationary phase is obtained by linking a simple derivative of l -lactic acid, ( S )-(—)-(2-phenylcarbamoyloxy)propionic acid, to γ-aminopropylsilanized silica gel. N-(3,5-Dinitrobenzoyl)amino acid methyl esters, were separated on the new phase with separation factors between 1.2 and 1.5.

Synthesis, chiroptical properties, and their theoretical simulation of some highly rotating benzotricamphor derivatives.

The large molecules 1-3 (69, 90, and 102 atoms, respectively), prepared by cyclotrimerization of enantiomerically pure derivatives of (-)-bornyl acetate, show intense ECD spectra, high optical rotation (OR) values (200-1300, in absolute value) dominated in sign and order of magnitude by the lowest-energy Cotton effects, that is, they are the ideal candidates to test the reliability of our approximate (TDDFT/B3LYP/6-31G* or smaller basis set) approach to the calculation of chiroptical properties. As a matter of fact, a correct simulation of the OR values and ECD spectra of 1 and 2 can be obtained even using STO-3G basis set and semiempirical or molecular mechanics input geometries: for 1, at the TDDFT/B3LYP/STO-3G level, the OR values are of the order of 500-550, versus an experimental value ranging between 660 and 690, depending on the solvent. On the contrary, the case of 3 (exp. OR between -1330 and -1500) is really complex (for instance, the OR values range between -3216 and -729 (TDDFT/B3LYP/6-31G* calculations) or -1824 and -444 (TDDFT/B3LYP/STO-3G calculations)), making the comparison between calculated and experimental values more difficult. The behavior of 3 is due to its molecular flexibility, whereas 1 is a really rigid molecules and 2 behaves (vide infra) as it were a rigid system. These observations strongly indicate that the conformational freedom constitutes one of the major difficulties for a correct but simple simulation of the chiroptical properties.