Gianfranco Cainelli

Solvent effects on stereoselectivity: more than just an environment

Stereoselectivity is a major topic in organic synthesis. Intensive investigations into the role of solvents on diastereo- and enantioselective reactions, as well as temperature-dependent measurements of diastereomeric and enantiomeric ratios, have shed light on the existence of dynamic solvation effects. In this tutorial review, several examples of non-linear Eyring plots in stereoselective nucleophilic additions, cycloadditions, photochemical and enzymatic reactions are reported. Experimental data and spectroscopic analyses obtained in aliphatic and aromatic hydrocarbons, halohydrocarbons, ethers and mixtures lead to the formulation of a hypothesis on the inversion temperature phenomenon as being due to an equilibrium between distinct solute-solvent clusters, which are the real reactive species in solution.

Inversion of configuration of alcohols through nucleophilic displacement promoted by nitrate ions.

Abstract Inversion of configuration of hydroxy functionalities in biologically significant structures has been performed under mild conditions through nucleophilic displacement by nitrate ion.

Chemistry of α-halometal compounds: Bromolithiummethane, synthesis of epoxides from aldehydes and ketones

Abstract The reaction between bromolithiummethane and carbonyl compounds has been studied. The organometallic species has been generated in situ by reacting dibromomethane and butyllithium, lithium suspension or amalgam in THF. Aliphatic, alicyclic and aromatic aldehydes and ketones give rise to the corresponding epoxides generally in satisfactory yields, α,β-unsaturated carbonyl compounds do not react under the mentioned conditions and this is useful if selectivity is required. The influence of the solvent on the reaction course is also discussed.

A theoretical study of the allyllithium ion-pair

Abstract Ab initio SCF computations have been performed on allyllithium using STO/3G atomic orbitals. Both the covalent and the ion-pair structures have been investigated and their energies minimized with respect to most of the geometrical parameters. The ion-pair structure is found to be more stable by 8 kcal/mol and a simple bonding scheme leads to the interpretation of its stability. The allyllithium molecule coordinated to two water molecules has also been studied to determine the effect of the solvent on the allyllithium bond.

A synthetic approach to azetidinones from nitriles and lithiumtriethoxyaluminium hydride.

Abstract A convenient one-pot process for direct conversion of nitriles to 3,4-disubstituted azetidinones has been developed.

ACYCLIC STEREOCONTROL IN THE ADDITION OF TRIMETHYLSILYL CYANIDE TO N-SUBSTITUTED IMINES OF (2S)-LACTIC ALDEHYDE

Abstract The cyanosilylation of a series of N -substituted lactaldehyde imines is reported. The trimethylsilylcyanide addition affords optically active α-amino nitriles. All the imines show a syn diastereofacial selectivity that is maintained irrespective to the nature of the Lewis acid employed and even remains in the noncatalyzed reaction.

Chemistry of α-halometalcompounds : A general method for obtaining epoxides from aldehydes and ketones

Abstract A general oxirane synthesis from a geminal dibromide and a carbonyl compound was studied. The reaction proceeds through an α-bromolithium species, most conveniently generated by reacting a geminal dihalogenide (e.g. ethylidene, isopropylidene, benzylidene bromide and ethyl dibromoacetate) and butyllitium or lithium suspended in THF. Aliphatic, alicyclic and aromatic aldehydes and ketones give rise to the corresponding epoxides, in good yields.

Acyclic stereocontrol with O-protected 2S-hydroxy-propanal: Solvent effect.

Abstract The dependence of diastereofacial selectivity on the nature of ether solvents in addition reactions of homochiral O-protected lactic aldehyde with organomagnesium reagents is reported.

New Polyphenolic β-Lactams with Antioxidant Activity

Novel 4‐alkylidene‐β‐lactams with a polyphenolic side chain were synthesized and evaluated as radical scavengers. We have undertaken a detailed study of the antioxidant activity in vitro with chemical and biological testing of the new β‐lactams and of the corresponding methyl polyhydroxy benzoates. Antioxidant activity of β‐lactams and methyl benzoates was measured with the Briggs–Rauscher oscillating reaction, the TEAC (Trolox® Equivalent Antioxidant Capacity) assay, and as ability to inhibit ROS (=Reactive Oxygen Species) production on myoblast H9c2 cells. The results were discussed with regard to mechanism and correlated with structural parameters.

Synthesis of novel 4-(1-ethoxycarbonyl-methylidene)-azetidin-2-ones via a Lewis acid-catalyzed reaction of ethyl diazoacetate

Treatment of (3R,4R,1′R)-3-[1-(t-butyldimethylsilyloxy)ethyl]-4-acetoxy-azetidin-2-one with ethyl diazoacetate in the presence of a Lewis acid such as TiCl4, TiF4, AlCl3 or SnCl4 affords the novel (3S,1′R)-3-[1-(t-butyldimethylsilyloxy)ethyl]-4(1-ethoxycarbonyl-methylidene)-azetidin-2-one as an E and/or Z isomer.