Transition state modelling of the aldol reaction of Z enol borinates with chiral α-methyl aldehydes suggests that three transition structures (F, AF, R) play a dominant role in controlling π-facial selectivity. The 'Felkin' structure (F) is characterized by Me-CH---C(O)-C* and CH---C(O)-C*-Me dihedral angles of about -60°/65° and +100°. The 'Roush' structure (R) has values of -65°/-65° and ± 175°/180°, while the 'Anti-Felkin/ one (AF) has values of +60°/+65° and about +50°. Our analysis suggests that nonabonded interactions play the most important role in determining aldehyde diastereofacial selectivity in the reactions with Z enolates, and that stereoelectronic effects are possibly overridden by steric effects. Reactions with aldehydes bearing relatively small and 'flat' substituents (Ph-, H 2C=CH-, Me 2C=CH-) are 3,4-syn selective ('Felkin' selective) while reactions with aldehydes bearing bulkier groups (various alkyls) are 3,4-anti selective ('Anti-Felkin' selective). This result is essentially due to destabilization of both (F) and (R) structures. In particular, in order to relieve strain-energy structure (F) opens the CH---C(O)-C°-Me dihedral angle from +60° to ca. +100°. In this way the bulky substituents (alkyls) are pushed towards the aldehyde hydrogen. In the (AF) structure the CH---C(O)-C°-Me dihedral angle is around +50° and the [aldehyde hydrogen-alkyl] interaction disappears. Enolate aggregation and chelation effects in the case of lithium enolates can possibly explain discrepancies observed between lithium and boron enolates and between the experimental ratios and the force field-predicted ratios.
Gennari, C., Vieth, S., Comotti, A., Vulpetti, A., Goodman, J., Paterson, I. (1992). Diastereofacial selectivity in the aldol reactions of chiral α-methyl aldehydes: A computer modelling approach. TETRAHEDRON, 48(21), 4439-4458 [10.1016/S0040-4020(01)80452-X].
Diastereofacial selectivity in the aldol reactions of chiral α-methyl aldehydes: A computer modelling approach
COMOTTI, ANGIOLINA;
1992
Abstract
Transition state modelling of the aldol reaction of Z enol borinates with chiral α-methyl aldehydes suggests that three transition structures (F, AF, R) play a dominant role in controlling π-facial selectivity. The 'Felkin' structure (F) is characterized by Me-CH---C(O)-C* and CH---C(O)-C*-Me dihedral angles of about -60°/65° and +100°. The 'Roush' structure (R) has values of -65°/-65° and ± 175°/180°, while the 'Anti-Felkin/ one (AF) has values of +60°/+65° and about +50°. Our analysis suggests that nonabonded interactions play the most important role in determining aldehyde diastereofacial selectivity in the reactions with Z enolates, and that stereoelectronic effects are possibly overridden by steric effects. Reactions with aldehydes bearing relatively small and 'flat' substituents (Ph-, H 2C=CH-, Me 2C=CH-) are 3,4-syn selective ('Felkin' selective) while reactions with aldehydes bearing bulkier groups (various alkyls) are 3,4-anti selective ('Anti-Felkin' selective). This result is essentially due to destabilization of both (F) and (R) structures. In particular, in order to relieve strain-energy structure (F) opens the CH---C(O)-C°-Me dihedral angle from +60° to ca. +100°. In this way the bulky substituents (alkyls) are pushed towards the aldehyde hydrogen. In the (AF) structure the CH---C(O)-C°-Me dihedral angle is around +50° and the [aldehyde hydrogen-alkyl] interaction disappears. Enolate aggregation and chelation effects in the case of lithium enolates can possibly explain discrepancies observed between lithium and boron enolates and between the experimental ratios and the force field-predicted ratios.
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