Dual Stereoselectivity in the Dialkylzinc Reaction Using(—)-β-Pinene Derived Amino Alcohol Chiral Auxiliaries

摘要

(+)-Nopinone, prepared from naturally occurring (—)-/3-pinene, was converted to the two regioisomeric aminoalcohols 3-MAP and 2-MAP in very good yield and excellent isomeric purity. Amino alcohol 3-MAP wassynthesized by converting (+)-nopinone to the corresponding a-ketooxime. This was reduced to the primaryamino alcohol and was converted to the morpholino group through a simple substitution reaction. 3-MAPwas characterized by X-ray crystallography, which displayed the rigidity of the pinane framework. Aminoalcohol 2-MAP was prepared from its trans isomer 2, which in turn was synthesized via hydroboration/oxidation of the morpholine enamine of (+)-nopinone. Two-dimensional NMR was used to characterize aminoalcohol 2-MAP, and NOE was used to confirm its relative stereochemistry. These amino alcohols wereemployed as chiral auxiliaries in the addition of diethylzinc to benzaldehyde to obtain near-quantitativeasymmetric induction in the products. The use of 3-MAP yielded (S)-phenylpropanol in 99% ee, and itsregioisomer 2-MAP gave the opposite enantiomer, (R)-phenylpropanol, also in 99% ee. Other aromatic,aliphatic, and 043-unsaturated aldehydes were implemented in this method, affording secondary alcohols inhigh yield and enantiomeric excess. Amino alcohols 2-MAP and 3-MAP were also found to be useful in thedimethylzinc addition reaction, both catalyzing the addition to benzaldehyde with nearly quantitative ee.Regioisomeric amino alcohols 2-MAP and 3-MAP, even though they were prepared from one enantiomer ofnopinone, provide antipodal enantiofacial selectivity in the dialkylzinc addition reaction. This circumvents thenecessity to synthesize amino alcohols derived from (—)-nopinone, which in turn requires the unnatural (+)-P-pinene. Possible mechanistic insights are offered to explain the dual stereoselectivity observed in thediethylzinc addition reaction involving regioisomeric, pseudo-enantiomeric amino alcohols 3-MAP and 2-MAP.