Diastereoselective Synthesis of (+/-)-1,2-Diphenyl-1,2-propanediol. A Discovery-Based Grignard Reaction Suitable for a Large Organic Lab Course

Abstract

We have developed an undergraduate organic laboratory experiment that probes the diastereoselectivity of the reaction between a Grignard reagent and a common, inexpensive α-chiral ketone. Students isolate a single diastereomer of (+/-)-1,2-diphenyl-1,2-propanediol by treatment of (+/-)-benzoin with MeMgI. Since the mp ranges of the two possible diol diastereomers differ by 10 °C, the reaction's diastereoselectivity can be established by mp determination alone, and it can be rationalized by the preferential addition of MeMgI to the least sterically hindered face of the carbonyl group in a rigid, five-membered cyclic intermediate (the "Cram chelate model"). This experiment is an interesting alternative to traditional Grignard experiments, is operationally straightforward and easily performed in large lab courses, and introduces students to π-facial discrimination by having them establish the stereochemical course of kinetically controlled nucleophilic addition to a carbonyl.

Probing the Reactivity of Cyclic N,O-Acetals versus Cyclic O,O-Acetals with NaBH4 and CH3MgI

“…After cooling to room temperature, the reaction mixture is dissolved in an organic solvent, transferred to a large test tube, and washed with water to remove the excess 2-(methylamino)­ethanol. Subsequent reactions with NaBH 4 and CH 3 MgI were performed via procedures like those previously reported. , Complete experimental details for each substrate, student handouts, and full-scale student-generated spectral data for all reactants and reaction products are provided in the Supporting Information.…”

“…All students had practice with basic spectral procedures like those previously reported. 13,14 Complete experimental details for each substrate, student handouts, and full-scale student-generated spectral data for all reactants and reaction products are provided in the Supporting Information. By analyzing spectra of the starting substrate and respective products, 37 students from two laboratory sections answered a set of questions (Supporting Information) asking them to establish the structures of products from reaction of their N,O-acetal substrate with NaBH 4 and CH 3 MgI, citing NMR, IR, and MS data to support their conclusions, and to propose a reasonable mechanism for product formation.…”

Investigating a Chemoselective Grignard Reaction in an Undergraduate Discovery Lab To Predict Reactivity and Final Products

“…Figure 1 shows the GC of the starting material (1), potential products (3,5), and product from the reaction. The retention time of the product matches the retention time of 3.…”

“…In teaching laboratories, students often prepare the Grignard reagent of bromobenzene and react it with carbon dioxide or benzophenone to yield benzoic acid or triphenylmethanol, respectively . Over the years, the emphasis on discovery-based pedagogy has resulted in the design of many new Grignard experiments. − However, until very recently, no attention has been given to experiments where students prepare a Grignard reagent selectively from the more reactive halogen in a dihalogenated species . Furthermore, most Grignard exercises result in the formation of highly predictable products such as tertiary alcohols.…”

Crystal structure of 2α-(1,1-diphenylethyl)-4-methyl-4α,5α-diphenyl-1,3-dioxolane: the result of a non-acid pinacol rearrangement

“…A sample of (AE)-1,2-diphenyl-1,2-propanediol (Ciaccio et al, 2001) was recrystallized in 1-butanol, as well as 2-butanol and 1-octanol. The solutions were mildly heated to obtain saturated solutions, cooled to room temperature and layered over…”