SolutionsThe Julia reaction and related processes
Exercise 1
In the Julia–Lythgoe reaction, why does the relative configuration of the β-acetoxy sulfone not matter? What is the difference, in this respect, from the Julia–Kocienski reaction?
During reduction with Na(Hg) intermediates form (radicals and carbanions, or an alkenyl sulfone by prior elimination of acetate) that lose the stereochemical information and equilibrate before the double bond forms; the product reflects the greater stability of the E alkene. In the Julia–Kocienski reaction there is no reduction: the addition of the carbanion to the aldehyde decides the configuration of the adduct, and the Smiles rearrangement and SO2 elimination are stereospecific, so selectivity depends on the diastereoselectivity of the addition (high for the anti adduct, which gives E, with potassium bases and polar solvents).
Exercise 2
How would you prepare the PT sulfone needed for the synthesis of resveratrol from 3,5-dimethoxybenzyl alcohol?
In two steps. First the sulfide is formed: Mitsunobu reaction of the alcohol with 1-phenyl-1H-tetrazole-5-thiol (PPh3, DEAD), or conversion of the alcohol into the bromide and substitution with the thiolate. Then the sulfide is oxidized to the sulfone, for example with excess m-CPBA or with H2O2 and ammonium molybdate.