Mirko Sarzi-Amade

Reactivity and endo–exo Selectivity in Diels–Alder Reaction of o-Quinodimethanes. An Experimental and DFT Computational Study

Abstract endo–exo Selectivity in Diels–Alder cycloadditions of several o-quinodimethanes (1–4) with acrylonitrile, 2-(5H)-furanone and N-methylmaleimide has been investigated in acetonitrile solution. Transition structures of the cycloaddition of the parent o-QDM (1), (E,E)-1,8-dimethyl-o-QDM (2), isoindene (3) and 2,3-dihydronaphthalene (4) with acrylonitrile and maleimide were located at both HF/6-31G∗ and B3LYP/6-31G∗ methods. Theoretical data reproduce fairly well both experimental absolute reaction rates and diastereoisomer ratios. The high endo selectivity has been rationalized mainly as a result of solvation effects (acetonitrile, PCM model) and reactant deformations. The latter is due to steric interactions.

Stereoselective epoxidation of cis-3,4-disubstituted-(CH2X)-cyclobutenes with dimethyldioxirane and peroxy acids. Experimental and computational evidence for a syn-orienting electrostatic effect

Abstract The epoxidation reactions of a series of cis-3,4-disustituted-(CH2X)-cyclobutenes 1–8 with dimethyldioxirane (DMD) and mClPBA have been investigated with both reagents. A remarkable syn diastereoselectivity in the formation of the epoxide has been observed for substrates bearing electron withdrawing substituents. Transition structures for epoxidations of 3,4-dimethylcyclobutene (1), diastereoisomeric 3,5-dioxa-4-thia-bicyclo[5.2.0]non-8-ene-4-oxides 7 and 8, and 3,4-bis(mesyloxymethyl)-1-cyclobutene (5) with dioxirane and peroxyformic acid have been located with the B3LYP/6–31G∗ method. Experimental dominant syn facial selectivity is rationalized mostly as a result of an electrostatic attractive interaction involving the peroxo oxygens of the oxidizing reagents and the positively charged homoallylic hydrogens of the olefins.

Hydrogen bonding effects in the epoxidation of propenol with dioxiranes. A DFT computational study

Abstract Potential energy surfaces for the epoxidations of 2-propen-1-ol with dioxirane (DHD) and dimethyldioxirane (DMD) were investigated at the B3LYP/6-31G ∗ level. Seven transition structures (TSs) were located for the reaction of DHD. The four chemically more significant TSs were located also for the reaction of DMD. Geometries and energies of two of them clearly demonstrate that stabilizing hydrogen bonding interactions can be at work and that they involve both the dioxirane oxygens. Calculations indicate that the electron attracting effect of the allylic hydroxy group has a relatively small rate retarding effect. Calculations predict higher reactivity for propenol with respect to propene reaction in gas phase but introduction of electrostatic solvation effects (acetone, Tomasi model) leads to reactivity reversal in substantial agreement with experimental data.

Transition structures for the stepwise insertion of oxygen into alkane tertiary CH bonds by dimethyldioxirane

Abstract Oxygen insertion into the isobutane CH bond by dimethyldioxirane 1 was computationally studied at the R(U)B3LYP level to address the mechanistic concerted-stepwise problem. We located genuine TSs, diradicaloid in nature, that can lead to final products via radical pair intermediates. These TSs have lower energies than their concerted counterpart. Thus, calculations support the viability of radical pair formation in the reaction of dioxiranes with alkanes.

DFT computational study of the epoxidation of olefins with dioxiranes

Abstract Transition structures (TSs) of the reactions of dioxirane and dimethyldioxirane with ethylene, propene, cis-2-butene and trans-2-butene were located with the B3LYP/6-31G∗ method. The TSs of the reactions of ethylene and cis-2-butene exhibit a symmetrical spiro butterfly structure with synchronous formation of the two new CO bonds and with substantial alignment of π bond axis with the breaking OO bond. In the case of propene and trans-2-butene a slight asynchrony in CO bond formation was predicted by calculations. Theoretical activation free enthalpies (gas phase) reproduce the experimental (acetone solution) higher reactivity of cis with respect to trans disubstituted alkenes which in turn are correctly predicted more reactive than monosubstituted alkenes. Also the calculated absolute activation free enthalpies, after correction for electrostatic solvation effects by single point SCRF calculation (Tomasi model), were found to be in reasonable accord with experimental data.

Reactions between Triazolinediones and Equilibrating Forms of Cycloheptatriene Derivatives Featuring 7,7-Spiro and 1,7-Fused Heterocyclic Rings

Nitrile oxide−azaheptafulvene adducts consist of rapidly equilibrating mixtures of fused (1) and spiro (2) isomers, the relative stabilities of which are nicely reproduced by B3LYP/6-31G* calculations. The reaction between these compounds and MTAD affords only two diastereomeric adducts [9 (dominant) and 10], both deriving from the reaction of MTAD with 1 even in cases in which that isomer could not be detected by NMR spectroscopy. These adducts are formal Diels−Alder adducts deriving from attacks on the two diastereotopic faces of the triene moiety of 1 and involving only the diene system adjacent to the amino substituent (N4−C4a=C5−C6=C7). The structures of the adducts are firmly supported by spectroscopic data and X-ray analysis, and so previous incorrect assignments are revised. The mechanism of the reaction between MTAD and 1 is briefly discussed.

Transition structures for one step nonconcerted oxygen insertion mechanism of oxidation of alkanes with trifluoroperoxyacetic acid

Abstract High level calculations (UB3LYP/6-31G ∗ ) on the oxygen insertion by trifluoroperoxyacetic acid (TFPA) into methane and isobutane C–H bonds strongly supports the viability of a one step nonconcerted mechanism. That is, the O–H bond forms first and the C–O bond formation commences afterwards, but only one first order saddle point, exhibiting high diradical character and strong polarization, is present on the energy profile of the minimum energy path. No minima corresponding to intermediates were located. IRC analysis suggests that the transition structure can collapse directly to products with retention of configuration at the alkane carbon center.

Facial selectivity in 1,3-dipolar cycloadditions to cis-3,4-dimethylcyclobutene. An experimental and computational study

Facial selectivity in 1,3-dipolar cycloaddition of diazomethane (2a), 3,4-dihydroisoquinoline N-oxide (2b), pyrroline N-oxide (2c), 5,5-dimethylpyrroline N-oxide (2d) and several nitrile oxides (2e–2j) with cis-3,4-dimethylcyclobutene (1) has been investigated. The stereochemistry of the cycloaddition of 2a, 2b–2d and encumbered nitrile oxides (2i and 2j) is controlled by steric interactions with dominant formation of the anti diastereoisomer. Syn and anti attack compete with each other in the cases of phenylglyoxylonitrile oxide and pyruvonitrile oxide (2g and 2h, respectively) thus disclosing the presence of contrasteric electronic syn orienting effects. Transition state structures of the cycloaddition of formonitrile oxide, diazomethane and methyleneamine N-oxide (nitrone) were located with both HF/6-31G* and B3LYP/6-31G* methods. The calculated relative free enthalpies of these transition states satisfactorily reproduce, at both levels, the observed facial selectivity while geometry data suggest a higher steric demand for the nitrone with respect to the other two dipoles. To the best of our knowledge this is the first study of diastereofacial selectivity in 1,3-dipolar cycloaddition with DFT theory.

Crystal structure of 9,12-ethano-12a-methoxycarbonyl-5, 8a,9,12,12a,12b-hexahydro-6H-[1,2]dioxino[4′,5′:4,5] isoxazolo[3,2-a]isoquinoline, C17H19NO5

The title compound crystallizes in the space group P21/n, with a = 18.423(3), b = 9.628(3), c = 19.243(2) Å, β = 116.208(8)°, with two independent molecules in the asymmetric unit, which are not enantiomers. The chiral centers C8a, C9, C12, C12a, C12b are either S,R,S,R,R or R,S,R,S,S, respectively, because of the centric space group.