Theoretical study of regioselectivity in nucleophilic addition to unsymmetrical cyclic anhydrides. Intrinsic reactivity and influence of the cation

1981 ◽  
Vol 59 (16) ◽  
pp. 2457-2462 ◽  
Author(s):  
Margaret M. Kayser ◽  
Odile Eisenstein
Keyword(s):  
Carbonyl Group ◽  
Nucleophilic Addition ◽  
Nucleophilic Attack ◽  
Dominant Factor ◽  
Molecular Orbital Calculations ◽  
Optimum Position ◽  
Cyclic Anhydrides ◽  
Intrinsic Reactivity ◽  
Reaction Media ◽  
Phthalic Anhydrides

Ab initio molecular orbital calculations have been carried out for the series of succinic, maleic, and phthalic anhydrides unsymmetrically substituted with CH3, CH3O, Cl, F, and CN. The size of the LUMO coefficient on the carbon atom of the carbonyl group provides a reliable guide to the relative reactivities of the two carbonyl functions. The predictions based on the intrinsic reactivities are in good agreement with the regioselectivities observed in metal hydride reductions of succinic anhydrides. In the series of maleic and phthalic anhydrides the above considerations are applicable only to methyl derivatives. The compounds substituted with lone pairs-bearing groups (OCH3, Cl, F) form stable chelates with the cations present in the reaction media. Since the chelated carbonyl group is strongly activated toward the nucleophilic addition, the "bridging" effect is the dominant factor controlling orientation of hydride addition. The optimum position for the nucleophilic attack in cyclic anhydrides was calculated. The results confirm the generality of the nonperpendicular, restricted path of nucleophilic attack on the carbonyl group in succinic anhydride.

Changing regioselectivity patterns in metal hydride reductions of unsymmetrically substituted cyclic anhydrides

1983 ◽  
Vol 61 (3) ◽  
pp. 439-441 ◽  
Author(s):  
Margaret M. Kayser ◽  
Judith Salvador ◽  
Peter Morand
Keyword(s):  
Carbonyl Group ◽  
Metal Hydride ◽  
Nucleophilic Additions ◽  
Substrate Molecule ◽  
Parent Molecule ◽  
Cyclic Anhydrides ◽  
Intrinsic Reactivity

A study of L- and K-selectride reductions of unsymmetrical cyclic anhydrides attached to six-membered rings and to bridged six-membered systems sheds a new light on the effect of the conformation of the substrate molecule on the regioselectivity of metal hydride reductions. Thus, in addition to intrinsic reactivity of the carbonyl group, the antiperiplanar effect, and steric congestion, the conformation of the parent molecule should be considered in predicting regioselectivity of nucleophilic additions to cyclic anhydrides.

Metal hydride reductions of unsymmetrically substituted cyclic anhydrides attached to strained ring systems

1982 ◽  
Vol 60 (10) ◽  
pp. 1199-1206 ◽  
Author(s):  
Margaret M. Kayser ◽  
Judith Salvador ◽  
Peter Morand ◽  
H. G. Krishnamurty
Keyword(s):  
Carbonyl Group ◽  
Metal Hydride ◽  
Theoretical Calculations ◽  
Ring Systems ◽  
Hydride Reduction ◽  
Cyclic Anhydrides ◽  
Intrinsic Reactivity

A dramatic reversal in regioselectivity is observed in the metal hydride reduction of unsymmetrical cyclic anhydrides such as 2,3, and 4 compared to cyclic anhydrides attached to bridged ring systems (e.g. 1). The synthesis of model cyclic anhydrides attached to strained rings is described and the ratios of isomeric lactones obtained upon reduction with metal hydride are reported. On the basis of theoretical calculations and, taking into account the intrinsic reactivity of the carbonyl group, the antiperiplanar effect, and steric congestion, an explanation is offered for the regioselectivity observed in the reduction of these compounds.

Sterically hindering the trajectory of nucleophilic attack towards p-benzynes by a properly oriented hydrogen atom: An approach to achieve regioselectivity

2021 ◽  
Author(s):  
Monisha Singha ◽  
Prabuddha Bhattacharya ◽  
Debashis Ray ◽  
Amit Basak
Keyword(s):  
Hydrogen Atom ◽  
Nucleophilic Addition ◽  
Nucleophilic Attack ◽  
Bergman Cyclization ◽  
Keen Interest

Nucleophilic addition to p-benzynes, derived via Bergman Cyclization has become a topic of keen interest. Studying the regioselectivity in such addition can reveal important information regarding the parameters controlling such...

On the regioselectivity of the condensation of stabilized phosphoylids with 3-substituted phthalic anhydrides

1989 ◽  
Vol 67 (4) ◽  
pp. 569-573 ◽  
Author(s):  
Livain Breau ◽  
Margaret M. Kayser
Keyword(s):  
Oxygen Atom ◽  
Transition State ◽  
Carbonyl Group ◽  
Lewis Base ◽  
Carbonyl Function ◽  
Deficient Phosphorus ◽  
Phthalic Anhydrides

Condensations of stabilized phosphorane 1 with 3-substituted phthalic anhydrides were investigated. The importance of various effects influencing regio- and stereoselectivity of these reactions is discussed. It is proposed that the oxygen atom on the substituents in position 3 can act as a Lewis base toward the electron-deficient phosphorus of the ylid. The resulting complexation stabilizes the transition state for the reaction at the ortho carbonyl group, thus offsetting the usual steric and "push" effects, which favour attack at the meta carbonyl function. Keywords: Wittig condensations, phthalic anhydrides, regioselectivity, stereoselectivity.

Deboronation of New Clarithromycin-Benzo[c][1,2]oxaborole Conjugates

2019 ◽  
Vol 17 (2) ◽  
pp. 99-104
Author(s):  
Gennady B. Lapa ◽  
Elena B. Isakova ◽  
Elena B. Mirchink ◽  
Maria N. Preobrazhenskaya
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Modeling ◽  
Carbonyl Group ◽  
Nucleophilic Attack ◽  
Bacterial Strains ◽  
Antimicrobial Spectrum ◽  
Intramolecular Complex ◽  
Active Fragments ◽  
Proven Method ◽  
Antibacterial Spectrum

<P>Background: The conjugates of antibiotics are new molecules that might show new antibacterial spectrum and overcome resistance of insusceptible bacterial strains. Modification of known antibiotics like Clarithromycin with active fragments is laborious and proven method to overcome resistance of such strains. Methods: The conjugates of Clarithromycin and Benzo[c][1,2]oxaboroles were synthesized using long linkers to extend antimicrobial spectrum of this antibiotic. Results and Discussion: Unexpected intramolecular deboronation of these bioconjugated was found to occur when the linker contained two or more CH2-groups. Molecular modeling was used to understand the source of instability and show a possibility of intramolecular complex of carbonyl group at C-9 in Clarithromycin core and hydroxy-borole moiety. This could facilitate nucleophilic attack of methanol used in reactions to destroy benzo[c][1,2]oxaboroles fragments and leave stable hydroxyl-aryl molecules. Conclusion: The loss of boron from benzo[c][1,2]oxoborole fragments leads to the significant decrease of antimicrobial activity of synthesized antibiotics.</P>

Metal hydride reductions of unsymmetrical cyclic anhydrides. The importance of the antiperiplanar effect on the regioselectivity of these reactions

1982 ◽  
Vol 60 (10) ◽  
pp. 1192-1198 ◽  
Author(s):  
Margaret M. Kayser ◽  
Georges Wipff
Keyword(s):  
Carbonyl Group ◽  
Metal Hydride ◽  
Lower Energy ◽  
Succinic Anhydride ◽  
Chair Conformation ◽  
Nucleophilic Attack ◽  
Quantum Mechanical ◽  
Mechanical Study ◽  
Quantum Mechanical Study ◽  
Experimental Findings

A quantum mechanical study by the SCF abinitio method of the interaction of H− with methylsuccinic and 2,2-dimethylsuccinic anhydrides (naked and in the presence of a cation) suggests that nonperpendicular rearside attack cannot be the factor responsible for the regioselectivity of hydride transfer to the more sterically hindered carbonyl group. In this model, the nucleophilic attack at the less hindered carbonyl group is calculated to be of lower energy (with or without cation). Deformation of the planar succinic anhydride ring to the quasi-chair conformation is energetically favoured as it allows the nucleophile to attack both carbonyl functions antiperiplanar to a quasi axial C—H or C—C bond. The attack antiperiplanar to the C—CH3 bond is lower in energy than the attack antiperiplanar to the C—H bond suggesting that the reduction will occur at the sterically more hindered carbonyl group which is in agreement with the experimental findings.

Reactions of bridging C3 ligands in diiron complexes: Unconventional routes to new functionalized organic frames

2010 ◽  
Vol 82 (7) ◽  
pp. 1555-1568 ◽  
Author(s):  
Valerio Zanotti
Keyword(s):  
Functional Groups ◽  
Nucleophilic Addition ◽  
Metal Center ◽  
Unusual Reaction ◽  
Nucleophilic Attack ◽  
Double Bonds ◽  
Bridging Ligands ◽  
Reaction Patterns

Diiron complexes containing C3 ligands, such as vinyliminium and vinylalkylidene bridging units, display unusual reaction patterns, not observed when the same organic fragments are bound to a single metal center, or not coordinated. Bridging vinyliminium complexes [Fe2{μ-η1:η3-C(NMe2)CH=CR}(μ-CO)(CO)(Cp)2][SO3CF3] undergo nucleophilic addition at the iminium C or at α-C position, which is uncommon since non-coordinated vinyliminium species generally undergo conjugated (Michael type) nucleophilic attack. Likewise, bridging vinyliminium ligands undergo new and unusual transformations consisting of the deprotonation and replacement of the α-CH by a variety of functional groups. These reactions, resulting in the formation of C–C and C–heteroatom single and double bonds, produce new bridging ligands of the type [μ-C(NMe2)C(X)CR) (X = S, O, Se, SPh, CNMe, NNCHCO2Me]. Removal of the vinylalkylidene ligands from the bridging coordination is achieved by a [3 + 2] cycloaddition with alkynes. The reaction leads to the formation of ferrocenes containing one polysubstituted Cp ring, which results from the cycloaddition of the bridging C3 ligand with alkynes. This result suggests a new possible route for the synthesis of polyfunctionalized ferrocenes.

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