title: Dual stereoselectivity in the dialkylzinc reaction using (-)-beta-pinene derived amino alcohol chiral auxiliaries.
abstract: (+)-Nopinone, prepared from naturally occurring (-)-beta-pinene, was converted to the two regioisomeric amino alcohols 3-MAP and 2-MAP in very good yield and excellent isomeric purity. Amino alcohol 3-MAP was synthesized by converting (+)-nopinone to the corresponding alpha-ketooxime. This was reduced to the primary amino alcohol and was converted to the morpholino group through a simple substitution reaction. 3-MAP was characterized by X-ray crystallography, which displayed the rigidity of the pinane framework. Amino alcohol 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 amino alcohol 2-MAP, and NOE was used to confirm its relative stereochemistry. These amino alcohols were employed as chiral auxiliaries in the addition of diethylzinc to benzaldehyde to obtain near-quantitative asymmetric induction in the products. The use of 3-MAP yielded (S)-phenylpropanol in 99% ee, and its regioisomer 2-MAP gave the opposite enantiomer, (R)-phenylpropanol, also in 99% ee. Other aromatic, aliphatic, and alpha,beta-unsaturated aldehydes were implemented in this method, affording secondary alcohols in high yield and enantiomeric excess. Amino alcohols 2-MAP and 3-MAP were also found to be useful in the dimethylzinc 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 of nopinone, provide antipodal enantiofacial selectivity in the dialkylzinc addition reaction. This circumvents the necessity to synthesize amino alcohols derived from (-)-nopinone, which in turn requires the unnatural (+)-beta-pinene. Possible mechanistic insights are offered to explain the dual stereoselectivity observed in the diethylzinc addition reaction involving regioisomeric, pseudo-enantiomeric amino alcohols 3-MAP and 2-MAP.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Binder
authors.forename: April
authors.initials: A
authors.lastname: Bautista
authors.forename: Marek
authors.initials: M
authors.lastname: Zaidlewicz
authors.forename: Marek P
authors.initials: MP
authors.lastname: Krzemiński
authors.forename: Allen
authors.initials: A
authors.lastname: Oliver
authors.forename: Bakthan
authors.initials: B
authors.lastname: Singaram
mesh_terms: D000605:Amino Alcohols / Q000737:chemistry*; D000081008:Bicyclic Monoterpenes; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D039821:Monoterpenes / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc
chemical_list: D000605:Amino Alcohols; D000081008:Bicyclic Monoterpenes; D001643:Bridged Bicyclo Compounds; D039821:Monoterpenes; D009942:Organometallic Compounds; C010789:beta-pinene; C511262:dimethylzinc; D015032:Zinc