Co-host: The Chemical Society of Japan, The Society of Synthetic Organic Chemistry, Japan (Cooperation)
The origin of facial diastereoselection has attracted active debate and most arguments were, as typified by the Cieplak model and the Felkin-Anh model, based on the premise that transition state stabilization be essential. However, we found that observed diastereoselectivities in LiAlH4 reduction of α-substituted-ketone are exactly opposite to the predictions made by the Felkin-Anh model. Moreover, ab initio calculation showed that the transition structures are quite different from that suggested by the Cieplak model. Structural analysis of optimized transition states has revealed that coordination of both carbonyl and methoxy oxygen atoms to lithium significantly stabilize transition states and largely affect the selectivities. In addition, IRC calculation suggested that the coordination has been already arisen at the initial stage, which cause difference in the accessibility of hydride between two carbonyl faces.
