Quantum Mechanical Models Correlating Structure with Selectivity:  Predicting the Enantioselectivity of β-Amino Alcohol Catalysts in Aldehyde Alkylation

• Published in: Journal of the American Chemical Society 2003-06, Vol.125 (22), p.6614-6615
• Main Authors: Kozlowski, Marisa C, Dixon, Steven L, Panda, Manoranjan, Lauri, Giorgio
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Alkylation; Amino Alcohols - chemistry; Catalysis; Chemistry; Exact sciences and technology; Kinetics and mechanisms; Models, Molecular; Organic chemistry; Quantum Theory; Reactivity and mechanisms; Stereoisomerism; Structure-Activity Relationship; Substrate Specificity; Thermodynamics
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0293195

Quantitative structure selectivity relationship (QSSR) models are described that provide consistently reliable predictions for the asymmetric addition of Et2Zn to PhCHO catalyzed by β-amino alcohols. Statistically valid two-variable linear regression models that correlate the structures of the chiral catalysts with their enantioselectivities are obtained from three-dimensional physical property grids. The strength of the present method is that statistical models obtained from a small set of experimentally determined selectivities and relatively simple theoretical calculations yield selectivity predictions that are as accurate as those derived from higher-level calculations of transition-structure energies. Only minutes of computing time are required. Simple models are obtained which permit straightforward physical interpretation and generate realistic predictions.