Title:Hendrickson Reagent Induced Rearrangement of Aryl Propargyl Alcohols To α,β-Unsaturated Aldehydes
VOLUME: 15 ISSUE: 10
Author(s):Ziad Moussa* and Ateyatallah Aljuhani
Affiliation:Department of Chemistry, Faculty of Science, Taibah University, Almadinah Almunawarrah, P.O. Box 30002, Department of Chemistry, Faculty of Science, Taibah University, Almadinah Almunawarrah, P.O. Box 30002
Keywords:Hendrickson reagent, triphenylphosphine oxide, triflic anhydride, aryl propargyl alcohols, α, β-unsaturated aldehydes,
mitsunobu, reagent.
Abstract:The Hendrickson reagent (triphenylphosphonium anhydride trifluoromethanesulfonate),
prepared from the reaction of triphenylphosphine oxide (Ph3PO) and triflic anhydride (Tf2O) (2:1
stoichiometry), promotes dehydrations and various coupling reactions. The reagent has been used to
transform oximes to nitriles and to prepare esters, amides and many other functional groups through
the intermediacy of an alkoxyphosphonium salt. The reagent proved useful in heterocycle synthesis of
thiazolines, imidazolines, quinoline precursors, isoquinolines, β-carbolines, phenanthridines, 11Hindolo[
3,2-c]quinolines, quinoline-lactones, furoquinolinones, and indolizino[1,2-b]quinolin-9(11H)-
ones. Moreover, the reagent has been key to the successful total synthesis of several natural products.
Aryl propargyl alcohols with a terminal α-acetylenic group undergo rapid conversion to the corresponding
α,β-unsaturated aldehydes at room temperature in dichloromethane in the presence of one
equivalent of triphenylphosphonium anhydride trifluoromethanesulfonate. The reaction involved adding
freshly distilled Tf2O (1.0 mmol) to a solution of Ph3PO (2.0 mmol) in CH2Cl2 (10 mL) at 0 oC under
N2 atmosphere. After stirring for 10 min, the propargyl alcohol (1.0 mmol) was added as a CH2Cl2
solution (2 mL), followed by the addition of water and Et3N (2.0 mmol) and further stirring at room
temperature for 1h. Subsequent workup with 5% NaHCO3 (20 mL) and purification afforded α,β-
unsaturated aldehydes. Eighteen aryl propargyl alcohol substrates with a terminal α-acetylenic group
were transformed in good to excellent yields (71-85%) to enals. The methodology proved successful
with secondary and tertiary alcohols with stereoselectivity favouring exclusively the E isomer. All the
synthesized compounds are known and were characterized (1H, 13C, and M.P) and compared to literature
values. The method offers several advantages such as exclusive stereoselectivity, short reaction
time, good yield, mild reaction conditions, and simple operational procedure.
