[52509-14-5] · C22H22BrO2P · (1,3-Dioxolan-2-ylmethyl)triphenylphosphonium Bromide · (MW 429.31)
(generation of the
nonstabilized ylide (1,3-dioxolan-2-ylmethylene)triphenylphosphorane for Wittig alkenation; synthesis of masked a,b-unsaturated aldehydes from aldehydes; reagent for two-carbon chain homologation1)
Physical Data: mp 193-195 °C.
Form Supplied in: white solid, 98%.
Preparative Method: from 2-bromomethyl-1,3-dioxolane and triphenylphosphine at 100 °C (36 h).2
Purification: recrystallized from methylene chloride/ether.2
This phosphonium salt reacts with base to give (1,3-dioxolan-2-ylmethylene)triphenylphosphorane, which is used in situ. Wittig reaction of this nonstabilized phosphorus ylide with aldehydes affords a,b-unsaturated acetals; acidic hydrolysis then provides the corresponding aldehydes. The alkene stereochemistry obtained is highly dependent on the base or solvent used. (E)-Alkenes are predominant with lithium methoxide or potassium carbonate in DMF (e.g. eq 1).2-6 Reactions of the ylide with ketones are generally poor.
Fraser-Reid and co-workers studied the stereoselectivity of this reagent in reactions with benzaldehyde involving different bases. When the phosphorane was prepared in THF with n-Butyllithium, only the (E)-alkene is formed. With dimsylsodium (Sodium Methylsulfinylmethylide) in DMSO a 3:1 ratio of (Z)- to (E)-isomers is obtained, while addition of THF to the DMSO reaction results in a 8:1 preference for the (Z)-isomer.7 These reaction conditions have been applied to ansamycin precursors (eq 2).7-9
Also, whereas a-alkoxy aldehydes usually furnish (E)-alkenes almost exclusively with Formylmethylenetriphenylphosphorane, Sakai et al. found that (1,3-dioxolan-2-ylmethylene)triphenylphosphorane, generated from the phosphonium reagent by using Sodium Hydride in THF-HMPA, gives mainly (Z)-alkenes (eq 3).10 Replacing the THF with DMF reduces this preference to ca. 75:25.
The Bestmann protocol with formylmethylenetriphenylphosphorane, which involves treatment with EtBr and NaOEt to form a diethyl acetal intermediate, offers a similar means for elaboration of aldehydes into a,b-unsaturated aldehydes chain-extended by two carbons, with high (Z) stereoselectivity.11,12 Related ylide reagents have also been used for such two-carbon homologations.13
David F. McComsey & Bruce E. Maryanoff
The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA