Modular Amino Alcohol Ligands Containing Bulky Alkyl Groups as Chiral Controllers for Et2Zn Addition to Aldehydes:  Illustration of a Design Principle

• Published in: Journal of organic chemistry Vol. 68; no. 8; pp. 3130 - 3138
• Main Authors: Jimeno, Ciril, Pastó, Mireia, Riera, Antoni, Pericàs, Miquel A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.04.2003; Amer Chemical Soc
• Subjects: Catalysis; Catalysts: preparations and properties; Chemistry; Chemistry, Organic; Exact sciences and technology; General and physical chemistry; Physical Sciences; Science & Technology; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; ORGANOZINC REAGENTS; REGIOCHEMICAL CONTROL; CHELATING PROCESSES; HIGHLY ENANTIOSELECTIVE ADDITION; DIETHYLZINC; RING-OPENING REACTIONS; DIALKYLZINC ADDITIONS; 1,2-EPOXIDES; CIS-OXIDES; FAMILY; Zinc Organic compounds; Catalytic reaction; Aminoalcohol; Enantioselectivity; Molecular structure; Steric effect; Transition state; Organic ligand; Steric hindrance; PM3 method; Aldehyde; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo034007l

A new family of enantiomerically pure (1S,2R)-1-alkyl-2-(dialkylamino)-3-(R-oxy)-1-propanols containing a very bulky alkyl substituent (tert-butyl or 1-adamantyl) on their hydrocarbon chains has been synthesized from the corresponding enantiopure epoxy alcohols, arising from the catalytic Sharpless epoxidation, by protection of the primary hydroxy group and subsequent regioselective ring opening of the epoxide by a secondary cyclic amine (C-2 attack). The performance of these amino alcohols as ligands for the catalytic enantioselective addition of diethylzinc to benzaldehyde has been studied, with enantioselectivities of 92−96% being recorded. The best performing ligands, those with a bulky R-oxy group, also depict a convenient activity and selectivity profile in the addition of Et2Zn to a representative family of aldehydes. An anomalous structure/enantioselectivity relationship of some ligands in the tert-butyl series has been studied using PM3 calculations, and conclusions have been drawn on the possible effects of including in modular designs structural fragments giving rise to a variety of rotameric transition states.