Molecular Modeling of Salt (Lithium Chloride) Effects on the Enantioselectivity of Diethylzinc Addition to Benzaldehyde in the Presence of Chiral β-Amino Alcohols

Abstract

Beta-amino alcohols (S,S,S)-1 and (R,R,S)-1, derived from cyclohexene oxide and containing alpha-phenylethyl auxiliaries, were examined as chiral promoters in the addition of diethylzinc to benzaldehyde. In agreement with literature precedent, the N-alpha-phenylethyl chiral auxiliary had no significant impact on enantioinduction, which is determined by the configuration of the framework's C(OH), with unlike induction. Contrary to some literature reports, stereoinduction by lithium salt derivatives of (S,S,S)-1 and (R,R,S)-1 was lower than that obtained with the free amino alcohol. Remarkable lithium chloride salt effects were observed in the reaction. In particular, an opposite chiral induction was found with (S,S,S)-1-Li(2) as ligand and in the presence of "inert" salt. N-Alkylated derivatives (S,S,S)-3-7 proved to be more efficient ligands, providing higher yields and enantioselectivities in the formation of carbinols (R)- or (S)-2. BP86/DN**//PM3 theoretical calculations proved remarkably successful in reproducing the experimental observations and permitted expansion of Noyori's catalytic cycle [J. Am. Chem. Soc. 1995, 117, 6327] to understand the relevant N-substitution and medium salt effects that determine the enantioselection in this catalytic asymmetric reaction.

NMR spectroscopy of organolithium compounds. XXVI—The aggregation behaviour of methyllithium in the presence of LiBr and LiI in diethyl ether and tetrahydrofuran

“…They have the magnitude typical for the two-bond shift observed earlier for D 3 CLi-LiI aggregates. 7 There is no systematic solvent effect, however for the first time an 2 H, 6 Li, isotope shift over four bonds was observed.…”

“…3 , Br, Br], respectively. Since deuterium in the CD 3 groups leads to high-frequency shifts, 7 the intensity distribution in the multiplets reflects the decreasing NOE effects for 6 Li with the decreasing number of CH 3 which indicates a deuterium-induced isotope shift over four bonds. Thus, under the conditions used in this study, we find that clusters A, B and C (Scheme 1, X D Br) are present in a molar ratio of 7 : 66 : 27.…”

“…The 1 H signal yield, considering the number of methyl groups per aggregate, 7 : 66 : 27, in excellent agreement with the 6 Li NMR results and the earlier work of Novak and Brown. 3 , CH 3 , Br]Br). Although one of the signals 2 and 3 is therefore without doubt due to cluster D, especially since D (X D I) was also found for the system H 3 CLi-LiI, 7 it is not clear if it is signal 2 or 3.…”

Kinetic Resolution of 1-Biaryl- and 1-(Pyridylphenyl)alkan-1-ols Catalysed by the Lipase B fromCandida antarctica

“…of Et 2 Zn in a 2 : 1 hexane-toluene mixture, in the presence of 6.0 mol % of alcohol (R)-6, according to a reported procedure. [22] After 24 h of reaction, benzaldehyde was completely consumed, and the produced 1-phenylpropan-1-ol (11) isolated with moderate to high yield (70 -92%). Reactions with ligands (R)-6c, l, m, q were not enantioselective and rac-11 was isolated in all cases.…”

Synthesis of chiral ligands containing the N-(S)-α-phenylethyl group and their evaluation as activators in the enantioselective addition of Et2Zn to benzaldehyde

“…(S,S,S)-1a and (R,R,S)-2 were prepared from cyclohexene oxide and (S)-a-phenylethylamine as described in the literature. 10, 11 Both aminoalcohols (S,S,S)-1a and (R,R,S)-2 (1 equiv) were treated separately with paraformaldehyde (6 equiv) in toluene and heated to reflux for 1.5 h, to afford (3aS,7aS)-and (3aR,7aR)-3-[(S)-a-phenylethyl]-octahydrobenzo[d]oxazoles (S,S,S)-4 and (R,R,S)-5 (96% and 93% yield, respectively, Scheme 2). Figure 1 shows the computer-generated X-ray diffraction structure of oxazole (S,S,S)-4, which shows like relative configurations between stereocenters at C(3a) and C(7a) and the known (S)-configured a-phenylethylamino group.…”