The design and development of highly enantioselective anti aldol reactions based on computer-aided transition-state modeling is reported. The new chiral boron ligand L = 6 was conceived based on its conformational preferences and on minimization of (+/-) double gauche pentane interactions. Modeling the transition structures for the aldol reaction of Z enolates 1 (L = 6) predicted a selectivity which is equal to or slightly lower than that calculated and experimentally tested with L = Ipc (isopinocampheyl) (see Table I). The predictions for E enol borinates (2) were synthetically more interesting: the new ligand (6) was calculated to be much more selective than Ipc (see Table II). Preparation of the boron reagent {[(Menth)CH2]2BCl-OEt2} (11) necessary for the synthesis of ligand 6-derived E enolates is reported, starting from commercially available enantiomerically pure (-)-menthone. Enolization of a range of cyclic and acyclic ketones {[(Menth)CH2],BCl-OEt2, Et3N, 1:1 CH2Cl2-Et2O, -78-degrees-C} and addition of an aldehyde (-78-degrees-C) gave anti aldols with high diastereoselectivity (86:14 to 100.0 anti:syn) and in good enantiomeric excess (56-88% ee). These conditions ensured high stereoselectivity toward formation of the E enolate (2), which then reacted preferentially by attack on the re face of the aldehyde (re:si 3.5:1 to 15.6:1). Also in the aldol reactions with methyl ketone enolates (3) the new reagent compared favorably with the existing methods.

THE RATIONAL DESIGN OF HIGHLY STEREOSELECTIVE BORON ENOLATES USING TRANSITION-STATE COMPUTER MODELING - A NOVEL, ASYMMETRIC ANTI-ALDOL REACTION FOR KETONES / C.M.A. GENNARI, C. HEWKIN, F. MOLINARI, A. BERNARDI, A. COMOTTI, J. GOODMAN, I. PATERSON. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - 57:19(1992), pp. 5173-5177.

THE RATIONAL DESIGN OF HIGHLY STEREOSELECTIVE BORON ENOLATES USING TRANSITION-STATE COMPUTER MODELING - A NOVEL, ASYMMETRIC ANTI-ALDOL REACTION FOR KETONES

C.M.A. GENNARI
Primo
;
F. MOLINARI;A. BERNARDI;
1992

Abstract

The design and development of highly enantioselective anti aldol reactions based on computer-aided transition-state modeling is reported. The new chiral boron ligand L = 6 was conceived based on its conformational preferences and on minimization of (+/-) double gauche pentane interactions. Modeling the transition structures for the aldol reaction of Z enolates 1 (L = 6) predicted a selectivity which is equal to or slightly lower than that calculated and experimentally tested with L = Ipc (isopinocampheyl) (see Table I). The predictions for E enol borinates (2) were synthetically more interesting: the new ligand (6) was calculated to be much more selective than Ipc (see Table II). Preparation of the boron reagent {[(Menth)CH2]2BCl-OEt2} (11) necessary for the synthesis of ligand 6-derived E enolates is reported, starting from commercially available enantiomerically pure (-)-menthone. Enolization of a range of cyclic and acyclic ketones {[(Menth)CH2],BCl-OEt2, Et3N, 1:1 CH2Cl2-Et2O, -78-degrees-C} and addition of an aldehyde (-78-degrees-C) gave anti aldols with high diastereoselectivity (86:14 to 100.0 anti:syn) and in good enantiomeric excess (56-88% ee). These conditions ensured high stereoselectivity toward formation of the E enolate (2), which then reacted preferentially by attack on the re face of the aldehyde (re:si 3.5:1 to 15.6:1). Also in the aldol reactions with methyl ketone enolates (3) the new reagent compared favorably with the existing methods.
Settore CHIM/06 - Chimica Organica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/175904
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