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.

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.

Reduction of cyclic anhydrides. II. Factors affecting regioselectivity of attack on the carbonyl group by metal hydrides

1978 ◽  
Vol 56 (11) ◽  
pp. 1524-1532 ◽  
Author(s):  
Margaret M. Kayser ◽  
Peter Morand
Keyword(s):  
Carbonyl Group ◽  
Metal Hydride ◽  
Metal Hydrides ◽  
Factors Affecting ◽  
Preferential Formation ◽  
Factors Influencing ◽  
Steric Factors ◽  
Cyclic Anhydrides ◽  
Experimental Findings ◽  
Carbonyl Function

The reduction of unsymmetrically substituted cyclic anhydrides with metal hydrides often leads to the preferential formation of one of the two possible lactones. In the light of recent experimental findings and theories concerning metal hydride addition to the carbonyl function, the electronic and steric factors influencing regioselectivity of cyclic anhydride reductions are discussed and an explanation for the observed patterns is proffered. Similar considerations may be extended to predict the major lactonic products in the reductions of various other unsymmetrical cyclic anhydrides.

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.

Regioselectivity of metal hydride reductions of unsymmetrically substituted cyclic anhydrides. systems where "steric hindrance along the preferred reaction path" rationalization is not applicable

1980 ◽  
Vol 58 (23) ◽  
pp. 2484-2490 ◽  
Author(s):  
Margaret M. Kayser ◽  
Peter Morand
Keyword(s):  
Transition State ◽  
Metal Hydride ◽  
Reaction Path ◽  
Steric Effects ◽  
Carbonyl Groups ◽  
Qualitative Interpretation ◽  
Alkaline Cation ◽  
Cyclic Anhydrides ◽  
Late Transition ◽  
Carbonyl Function

Metal hydride reductions of planar cyclic anhydrides such as methylmaleic or 3-substituted phthalic anhydrides occur preferentially at the sterically more hindered carbonyl function. This regioselectivity cannot be rationalized in terms of "the most favourable pathway for non-perpendicular attack by a nucleophile" since both carbonyl groups present are equally accessible to non-perpendicular approach. A study which takes into account the alkaline cation and inductive, mesomeric, and steric effects has been conducted for the reduction of several conjugated and aromatic anhydrides. A qualitative interprétation for the regioselectivities observed in these reductions (as well as in reductions already reported in the literature) is suggested. An early transition state for the catalyzed versus late transition state for the non-catalyzed process is proposed.

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