Transition state modelling of the aldol reaction of Z enol borinates with chiral alpha-methyl aldehydes (see Schemes 4 and 6) suggests that three transition structures (F, AF, R) play a dominant role in controlling pi-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-degrees/-65-degrees and +100-degrees. The "Roush" structure (R) has values of -60-degrees/-65-degrees and +/-175-degrees/180-degrees, while the "Anti-Felkin" one (AF) has values of +60-degrees/+65-degrees and about +50-degrees. Our analysis suggests that nonbonded 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-, H2C=CH-, Me2C=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) (see Tables 1 and 2). 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-degrees to ca. +100-degrees. 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-degrees 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.

DIASTEREOFACIAL SELECTIVITY IN THE ALDOL REACTIONS OF CHIRAL ALPHA-METHYL ALDEHYDES - A COMPUTER MODELING APPROACH / C.M.A. GENNARI, S. VIETH, A. COMOTTI, A. VULPETTI, J.M. GOODMAN, I. PATERSON. - In: TETRAHEDRON. - ISSN 0040-4020. - 48:21(1992), pp. 4439-4458.

DIASTEREOFACIAL SELECTIVITY IN THE ALDOL REACTIONS OF CHIRAL ALPHA-METHYL ALDEHYDES - A COMPUTER MODELING APPROACH

C.M.A. GENNARI
Primo
;
1992

Abstract

Transition state modelling of the aldol reaction of Z enol borinates with chiral alpha-methyl aldehydes (see Schemes 4 and 6) suggests that three transition structures (F, AF, R) play a dominant role in controlling pi-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-degrees/-65-degrees and +100-degrees. The "Roush" structure (R) has values of -60-degrees/-65-degrees and +/-175-degrees/180-degrees, while the "Anti-Felkin" one (AF) has values of +60-degrees/+65-degrees and about +50-degrees. Our analysis suggests that nonbonded 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-, H2C=CH-, Me2C=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) (see Tables 1 and 2). 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-degrees to ca. +100-degrees. 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-degrees 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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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/177136
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