Rationalization of Product Selectivities in Asymmetric Horner−Wadsworth−Emmons Reactions by Use of a New Method for Transition-State Modeling

• Published in: Journal of organic chemistry 1999-08, Vol.64 (16), p.5845-5852
• Main Authors: Norrby, Per-Ola, Brandt, Peter, Rein, Tobias
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo990318d

A new method for creating a transition-state force field, based on quantum chemical normal-mode analysis, is described. Except for distortions along the reaction coordinate, the potential energy surface around the TS is closely reproduced. The force field was used to rationalize the experimentally observed product selectivities in asymmetric Horner−Wadsworth−Emmons reactions between chiral phosphonates 1 and aldehydes 2−4. It was shown that if the transition states for the addition step (TS1) and for the subsequent ring closure to an oxaphosphetane (TS2) are both considered in the modeling, the product selectivity can be rationalized with good accuracy. The calculations supported the previously reported hypothesis that the overall product selectivities result from the combined influence of the chiral auxiliary, the α-stereocenter(s) in the aldehyde, and the phosphonate alkoxy groups. Somewhat unexpectedly, the modeling showed that in several cases the influence of the aldehyde α-stereocenter is even more pronounced in TS2 than in TS1. The combined influence of the chiral auxiliary and the aldehyde α-stereocenter(s) explains the general observation that (E)- and (Z)-alkenes are formed with opposite enantiotopic group preference from the same substrate.