Converting (±)-Benzoin to DL-Hydrobenzoin

Inspired by the Felkin-Anh (F-A) model as a predictor of the preferred diastereoselection in nucleophilic additions to α-chiral ketones, an undergraduate organic chemistry lab experiment has been developed in which students use a synthetic strategy based on the guidelines of this model to reverse the diastereoselectivity associated with the NaBH4 reduction of (±)-benzoin to afford dl-hydrobenzoin instead of meso-hydrobenzoin as the major product. They achieve this objective by first acylating the hydroxyl group of (±)-benzoin with trimethylacetyl chloride (also known as pivaloyl chloride) to create a group whose steric bulk would surpass that of the phenyl group on the α-carbon. Working in two groups, they then carry out the reduction of the ketone function of the resulting ketoester using two different reducing agents: one group uses NaBH4 /ethanol, a widely used metal hydride reagent for reduction of aldehydes and ketones, and the other uses Al(OiPr)3/2-propanol, a hydride transfer reagent used in the Meerwein-Ponndorf-Verley (MPV) reaction. Subsequently, students from both groups hydrolyze their hydroxy esters to afford dl- and meso-hydrobenzoins as the major and minor products, respectively. Students share 1H NMR spectra of their products and establish the relative population of each diastereomer present using NMR peak integration values. The reversed diastereoselectivity exhibited by the reactions in this experiment leading to dl-hydrobenzoin as the major product, not only highlights the importance of the F-A model as a powerful predictor of such stereoselective reductions, but also serves as a pedagogically valuable complement to a previously described discovery-based experiment that probes the diastereoselectivity in the NaBH4 reduction of (±)-benzoin that affords meso-hydrobenzoin as the major product.