Stefano Superchi

Absolute configurations of fungal and plant metabolites by chiroptical methods. ORD, ECD, and VCD studies on phyllostin, scytolide, and oxysporone.

The absolute configuration (AC) of the bioactive metabolites phyllostin (1) and scytolide (2), two hexahydro-1,4-benzodioxines produced by Phyllosticta cirsii, and oxysporone (3), a dihydrofuropyranone recently isolated from a strain of Diplodia africana, has been assigned by computational analysis of their optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) spectra. Computational prediction of ORD, ECD, and VCD allowed us to assign (3S,4aR,8S,8aR) AC to naturally occurring (-)-1, while (4aR,8S,8aR) AC was assigned to (-)-2 employing only ECD and VCD, because in this case ORD analysis turned out to be unsuitable for AC assignment. Theoretical prediction of both ORD and ECD spectra of 3 led to assignment of (4S,5R,6R) AC to (+)-3. In this case a satisfactory agreement between experimental and calculated VCD spectra was obtained only after taking into account solvent effects. This study shows that in the case of flexible and complex natural products only a concerted application of more than a single chiroptical technique permits unambiguous assignment of absolute configuration.

Noncovalent Organocatalysis: A Powerful Tool for the Nucleophilic Epoxidation of α-Ylideneoxindoles

A novel asymmetric nucleophilic epoxidation for α-ylideneoxindole esters has been successfully devised, resulting in enantioenriched spiro compounds with two new contiguous stereocenters. The employed (S)-α,α-diphenylprolinol functions as a bifunctional catalyst, creating a complex H-bond network in conjunction with a substrate and an oxidant.

Enantiopure dendrimers derived from the 1,1'-binaphthyl moiety: a correlation between chiroptical properties and conformation of the 1,1'-binaphthyl template

The absorption and CD spectra of a series of Frechet (compounds 7-10) and backfolding (compounds 11-12) dendrimers derived from enantiopure (S)-2,2′-dihydroxy-1,1′-binaphthalene have been recorded (THF) in the range 200-350 nm. All the compounds examined show a positive couplet between 200 and 240 nm (1B transition of the 2-naphthol chromophore), the intensity of which (Δϵmax of the low-energy branch) ranges between 100 and 40. By means of the DeVoe polarizability model the intensity of the 1B couplet has been calculated vs. the dihedral angle θ. This analysis provides θ angles of 95-110° for the Frechet dendrimers and 100-110° for the backfolding compounds. These values clearly indicate that the torsional angle θ, defined by the two naphthalene planes, never exceeds the critical value of 110°. This investigation confirms the wide utility of CD spectroscopy to provide geometrical information that cannot be obtained by other types of structural analysis.

Catalytic asymmetric oxidation of aryl methyl sulfides mediated by a (S,S)-1,2-diphenylethan-1,2-diol/titanium/water complex

Abstract The asymmetric oxidation of aryl methyl sulfides to sulfoxides with hydroperoxides has been achieved using catalytic amounts of the complex formed in situ between Ti( i -PrO) 4 , ( S , S )-diphenylethan-1,2-diol 1 and water. The sulfoxides are obtained in 60% yield and 67–80% enantiomeric excess.

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.

1,1′-Binaphthylazepine-based ligands for asymmetric catalysis. Part 1: Preparation and characterization of some new aminoalcohols and diamines

Abstract Starting from ( S )-1,1′-binaphthol, a series of ten novel enantiopure 1,1′-binaphthylazepine-based aminoalcohols and diamines 1a – 1j were efficiently prepared and fully characterized. These derivatives, having either only an atropisomeric bridged-binaphthyl backbone or an additional stereogenic carbon center, can be interesting ligands for asymmetric catalysis.

Towards a correlation of absolute configuration and chiroptical properties of alkyl aryl sulfoxides: a coupled-oscillator foundation of the empirical Mislow rule?

The absorption and circular dichroism (CD) data for a series of alkyl aryl sulfoxides 1-16 of known S configuration have been analyzed. The strong bathochromic effect exerted by the nitro group in the para position of the phenyl sulfoxides indicates that the sulfur atom acts as an electron donor moiety towards the phenyl ring. Such behavior requires a significant 2p(C)-3sp3(S) overlap, and therefore the phenyl (and p-substituted phenyl) sulfoxides 1-12, as well as the 2-naphthyl sulfoxides 15 and 16, must assume a conformation which permits such orbital overlap. The steric effect of the peri hydrogen in 1-naphthyl-substituted compounds 13 and 14 does not allow a conformation of this type, and in these compounds the above-mentioned 2p(C) and 3sp3(S) orbitals are positioned in almost orthogonal planes. This conformational difference is clearly shown by the absorption spectra: compounds 1-12, 15, and 16 show the lowest energy sigma --> sigma* transition of the sulfoxide chromophore at approximately 250 nm, indicating the existence of a conjugated S=O chromophore. In contrast, the corresponding absorption in 13 and 14 occurs at about 200 nm, indicating the presence of an isolated S=O chromophore. The CD spectra of 13 and 14 show a negative, couplet-like feature between 250 and 200 nm. This spectral feature can be interpreted in terms of exciton coupling between the allowed sigma --> sigma* transition of the isolated S=O chromophore at 200 nm and the 1B transition of the naphthalene chromophore. In fact, the Harada-Nakanishi rule predicts a negative CD couplet for an S-configured sulfoxide in the conformation found by UV analysis, as found experimentally. The CD spectrum of 13 is quantitatively reproduced by DeVoe coupled-oscillator calculations, strongly implying that a coupled-oscillator mechanism is operative in determining the optical activity of 13 and 14. This approach has also tentatively been extended to the conjugated sulfoxides 1-12, taking into account the coupling of the benzene chromophore 1La transition with the sigma --> sigma* transition of the S=O chromophore. In this case the Harada-Nakanishi rule also predicts a negative CD couplet for the S-configured sulfoxides, as found experimentally.

1,1′-Binaphthylazepine-based ligands for asymmetric catalysis. Part 2: New aminoalcohols as chiral ligands in the enantioselective addition of ZnEt2 to aromatic aldehydes

Abstract The new enantiopure 1,2-aminoalcohols 1b – 1h having 1,1′-binaphthylazepine skeleton have been tested as catalytic precursors in the enantioselective addition of ZnEt 2 to benzaldehyde. The best results were seen with ligand 1d , which owes its chirality only to the atropisomerism of the binaphthyl nucleus and does not have any stereogenic carbon atom. In the presence of 1d benzaldehyde was quickly and cleanly transformed to ( S )-1-phenylpropanol in 99% yield and 87% e.e. The same ligand was also used in the asymmetric ZnEt 2 addition to other aryl aldehydes giving rise to ( S )-1-arylpropanols in almost quantitative yields and e.e.s up to 90%.

Enantiopure p,p′-disubstituted 1,2-diphenylethane-1,2-diols as chiral inducers in the Ti-mediated oxidation of sulfides: a case of reversal of asymmetric induction by fluorine substitution

Abstract In the asymmetric oxidation of methyl p -tolyl sulfide, ( 2a ), and benzyl phenyl sulfide ( 2b ) by TBHP, mediated by a titanium complex with enantiopure (R,R)-p,p′ -disubstituted-1,2-diphenylethane-1,2-diols, both the unsubstituted diol (R,R) - 1a and the p -OMe substituted diol (R,R) - 1b lead to sulfoxides of S configuration, with ee up to 99%. On the contrary the p -CF 3 substituted ligand (R,R) - 1c leads to significantly lower ee and in the case of 2a a reversal of asymmetric induction is observed.

Monobenzylether of (R,R)-1,2-diphenylethane-1,2-diol as chiral auxiliary in the diastereoselective reduction of α-ketoesters

Abstract The α-ketoester 4a, prepared in 3 steps from (R,R)-1,2-diphenylethane-1,2-diol can be reduced with several agents providing the corresponding α-hydroxyester 5 with diastereoselectivities up to 56%. This selectivity has been interpreted as due to carbonyl face-shielding by the stacked OCH2Ph moiety of 4a.