Theory and Modeling of Stereoselective Organic Reactions

Abstract

Theoretical investigations of the transition structures of additions and cycloadditions reveal details about the geometries of bond-forming processes that are not directly accessible by experiment. The conformational analysis of transition states has been developed from theoretical generalizations about the preferred angle of attack by reagents on multiple bonds and predictions of conformations with respect to partially formed bonds. Qualitative rules for the prediction of the stereochemistries of organic reactions have been devised, and semi-empirical computational models have also been developed to predict the stereoselectivities of reactions of large organic molecules, such as nucleophilic additions to carbonyls, electrophilic hydroborations and cycloadditions, and intramolecular radical additions and cycloadditions.

Understanding the Polar Character Trend in a Series of Diels-Alder Reactions Using Molecular Quantum Similarity and Chemical Reactivity Descriptors

“…In this sense, the regiospecificity of such DA interactions can be defined by the molecular polarization parallel to the nodal plane of the orbitals produced by the ( ) and ( * ) DA interactions; therefore, the stereospecificity of such interactions can be associated with the electronic distortion perpendicular to the nodal plane of the orbitals produced by the HOMO-1 ( ), HOMO ( ), LUMO ( * ), and LUMO + 1 ( * ) interactions mixed, according to "principle of Orbital Distortion" [150], and these electronic interactions exceed to the steric effects, yielding the bonds in the cycloadducts respective. These results are consistent with the stereoselectivity analysis reported by Houk et al [151].…”

Fluorine‐Directed Diastereoselective Iodocyclizations

“…The formate ion approaches the alkene at an angle of around 1108, thus indicating attack on the backside of the s* CÀI bond. [10] As shown in Figure 3 for the ethyl-substituted I 2 -p complex, the second oxygen atom may be either proximal or distal to the alkene. A proximal orientation provides a stabilizing electrostatic interaction between the negatively charged oxygen atom and the positively charged carbon atoms of the I 2 -p complex.…”

A Practical Synthesis of (+)‐Biotin from L‐Cysteine

“…[15] The syn selectivity of the Strecker reaction may be accounted for by the Houk model shown in Figure 1. [16] Coordination of the hypervalent silicon or hydrogen atom to the imine nitrogen atom enables internal delivery of the cyanide to the imine from the opposite side of the bulky benzylamide group to provide syn-a-amino nitrile syn-5 stereoselectively.…”