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 (1 R,2 S,5 R )-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 R 1 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.