Elisabetta Vecchi

Steric and kinetic effects of changing solvent and reagent in grignard reactions on some 4-substituted cyclohexanones

Abstract The stereochemistry and relative rates of Grignard reactions on some 4R-substituted cyclohexanones (R=tBu, Me, OMe. CO2Me, OCOPh and Cl) have been determined under two separate reaction conditions (MeMgI in C6H6 and MeMgCl in THF). The results of our studies indicate that substrates containing an ester group have a higher reaction order in Grignard rcactant than other groups when reactions were carried out in the aromatic solvent. The same is not true for reactions carried out in THF. Both stereochemical product ratios and relative reaction rates are better understood assuming that compounds containing a polar group (OMe and Cl at least) react via a transition state possessing that group in the axial conformation.

Stereochemistry of grignard reactions on some conformationally mobile δ-keto esters: The effects of changing solvent and reactant

Abstract Methyl 4-methyl-5-oxo-hexanoate (4) and methyl 4-methyl-5-oxo-5-phenyl-pentanoate (5) yield mixtures of cis and trans tetrahydro-5, 6-dimethyl-6-phenyl-2H-pyran-2-one (6+7) on reacting with PhMgX and MeMgX, respectively. Ratios 6 7 were measured for reactions performed in benzene, diethyl ether (with XI) and tetrahydrofuran (with XCI). A comparison is made of the results obtained with those of methyl (2-oxo-cyclohexyl)-propionate (1). It is suggested that the ester group and the keto group can interact in the transition states of the reaction performed in the less polar solvent and that in polar solvents they are remote from one another during the reaction. These conformational changes are believed to be responsible for the observed stereochemical differences in the reactions.

Studies on the stereochemistry of addition reactions of cyclohexanones : A dichotomy in substituent effect depending on reaction conditions

Abstract The stereochemistry of addition reactions of 4-t-Bu, 4-OMe and 4-C1 cyclohexanones, determined under seven different reaction conditions is described. A dichotomy in the substituent influence on stereochemistry is outlined and discussed suggesting that it parallels the changes in reaction mechanism.

Does substituent's conformation influence the kinetics of reduction reactions on trans-4-X-decal-1-ones and to what extent?

Abstract Stereochemistry and relative rates k ax and k eq of reduction reactions on title compounds have been measured under five different reaction conditions (NaBH 4 in i -PrOH, LiBH 4 and NaAlH 4 in THF and LiAlH 4 in THF and in Et 2 O). Experiments indicate that axial substituents behave as far less electronegative than their equatorial counterpart in reactions at the equatorial side of molecules.

Studies on the stereochemistry of reduction reactions on 10-R substituted trans decal-2-Ones

Abstract Relative rates k ax and k eq of reduction reactions of title compounds (R=H, Me, CO 2 Et, Cl) have been measured in three different reaction conditions (LiAlH 4 , LiEt 3 BH, NaBH 4 ). We found that k eq decreases as the substituent electronegativity increases when lithium reactants are used and that k ax increases as the substituent electronegativity increases when sodium reactant is used. The synthesis of trans and cis 10 chloro-decal-2-ones is also described.

π-Face diastereoselection: stereochemistry and reactivity of reduction reactions on conformationally rigid substrates: 5-X-adamantan-2-ones and trans-10-X-decal-2-ones

Abstract Stereochemistry and relative rates k ax and k eq of addition reactions on title compounds have been measured under eight different reaction conditions (MeMgI in Et 2 O and C 6 H 6 , MeMgCl in THF, MeLi at 20 and −78°C, Me 2 Zn in Et 2 O, Me 3 Al in the ratio 1:1 reactant:substrate in toluene and Me 2 CuLi/MeLi in Et 2 O at −78°C). Our kinetic data do not fit with current theories of π-face diastereoselection.

Studies on the stereochemistry of addition reactions on cyclohexanones VII: The effect of the axial ester group on the reactivity of trans 2-decalones

Relative rates kax and keq of addition reactions to title compounds have been measured in eight different reaction conditions. The effect of changing the axial substituent in the position 3 and 4 to the carbonyl group from -H to -Me and -CO2R is described. Data show that stereochemical product ratios kaxkeq changes originate sometimes from uneven increase (or decrease) of both kax and keq and sometimes from their divergent change. This last case points to a different nucleophylic vs. electrophylic character of the axial and equatorial attack.

Steric and kinetic effects of changing solvent and reactant in grignard reactions: Conformationally mobile versus rigid δ-keto esters

Abstract trans-7α-carbomethoxy-decal-1-one (2) yields a mixture of the two oxy-esters 6 and 7 on reacting with MeMgX. Ratios 6 7 were measured for reactions performed in benzene (with X = I) and in THF (with X = Cl). The small variations of the ratios 6 7 as compared to those obtained in analogous experiments performed with methyl (2-oxo-cyclohexyl)-propionate 4 and methyl 4-methyl-5-oxo-hexanoate 5 suggest that conformational mobility plays a fundamental role in determining the variations of stereospecificity with varying the reaction conditions. Competitive Grignard reactions among 2,4 and 5 show that their reactivities are in the order 4>2>5 ( K 4 k 2 = 1.7; k 5 k 2 =0.8) when reactions are performed in benzene with X  I and 2>4>5 ( k 4 k 2 = 0.56; k 5 k 2 =0.25) when reactions are performed in THF with X  C1. The experimental data are interpreted in terms of anchimeric assistance given by the ester group to the reactions of the keto group in conformationally mobile δ-keto esters. The occurrence of this effect depends on the reaction conditions which can favour, or not, folded transition states.

To what extent does the substituent conformation influence the kinetics of addition reactions on 5X-bicyclo[4.4.0]decan-2-ones?

Abstract Stereochemistry and relative rates k ax and k eq of addition reactions on the title compounds have been measured under four different reaction conditions (CH 3 MgI in Et 2 O and C 6 H 6 , and CH 3 Li in Et 2 O at 20°C and −78°C). In strict accordance with previous findings we show that the axial substituents are far less electronegative than their equatorial counterparts in equatorial attack reactions. Axial attack, however, is independent of the substituent conformation.

Analysis of 1H and 13C NMR Spectra of cis- and trans-10-Chlorodecal-2-ones by 2D NMR Techniques

The 1H and 13C NMR chemical shift assignments of trans‐ and cis‐10‐chlorodecal‐2‐ones were based on 2D COSY and HETCOR experiments. The spectra were measured either in CDCl3 or in C6D6 to optimize the spectral dispersion (ASIS effect). Selective spin decoupling experiments were also performed.