Reagent Control of Geometric Selectivity and Enantiotopic Group Preference in Asymmetric Horner−Wadsworth−Emmons Reactions with meso-Dialdehydes

Results from asymmetric Horner−Wadsworth−Emmons reactions between chiral phosphonate reagents 3a − d, which contain (1R,2S,5R)-8-phenylmenthol as a chiral auxiliary, and meso-dialdehydes 6 and 14 are presented. It was found that both the geometric selectivities and the levels of asymmetric induction depended on the structure of the phosphonate (i.e., the alkyl group R1 in the phosphoryl unit) and to a certain extent also on the reaction conditions. Furthermore, the nature of the protecting group used on the α-oxygen substituent in dialdehydes 14 influenced the outcome somewhat. By an appropriate choice of reagent and conditions, either (E)- or (Z)-monoaddition products could be obtained geometrically pure and with good to excellent diastereoselectivities, in synthetically useful yields. Analyses of the absolute configurations of the products showed that the (E)-selective reagents (3a − c) and the (Z)-selective phosphonate 3d reacted at opposite enantiotopic carbonyl groups in the substrates. A mechanistic model which accounts for the products formed is presented.