5.2: Epoxidation of Allylic Alcohols
Epoxidation of allylic alcohols is a well developed practical process in asymmetric catalysis.
Titanium-Catalyzed Epoxidation
The Sharpless asymmetric epoxidation of allylic alcohol provides a powerful tool for the synthesis of optically active epoxy alcohol. For example, hexe-2-en-1-ol undergoes epoxidation to give chiral epoxy alcohols with 94% ee and 85% yield in presence of 5-10 mol% of Ti(O i Pr) 4 , L-(+)-DET and t -BuOOH (Scheme \(\PageIndex{1}\)). Using D-(-)-DET as chiral source the opposite enantiomer can be obtained with similar yield and enantioselectivity.
Examples:
In case the substrates having more double bonds, the allylic double bond can be oxidized. For example, the allylic double bond of geraniol can be selectively oxidized with 95% ee (Scheme \(\PageIndex{2}\)).
Mechanism
The reaction of titanium alkoxide with tartrate ligands leads to the formation of the dimers 1 and 4 that in the presence of t -BuOOH are converted into the intermediates 2 and 5 , respectively, by displacement of the isopropoxide and tartrate carbonyl groups (Scheme \(\PageIndex{3}\)-\(\PageIndex{4}\)). Reaction of 2 and 5 with allylic alcohol give the intermediates 3 and 6 , respectively. The stereochemistry of the epoxide is determined by the diastereomer of the chiral tartrate diester.
The product stereochemistry can be predicted using the model shown in Scheme \(\PageIndex{5}\).
Application
The reaction has been applied for the synthesis of a number of natural products, antibiotics and pharmaceuticals. For examples, the synthesis of the sex pheromone of gypsy moth ( Lymantria dispar ) (+)-disparlure 12 has been accomplished (Scheme \(\PageIndex{6}\)). The epoxidation of allyl alcohol 7 by Sharpless procedure affords optically active epoxy alchohol 8 with 95% ee that in presence of pyridinium dichlorochromate (PDC) gives chiral aldehyde 9 . The latter with Wittig salt 10 affords trans -alkene 11 that could be reduced using Pd/C to give the target (+)-disparlure 12 .
The Scheme \(\PageIndex{7}\) shows the use of the Sharpless asymmetric epoxidation for the synthesis of gastric inhibitor (S) -propanolol. The epoxidation of 3-(trimethylsilyl) prop-2-en-1-ol 13 affords epoxy alcohol 14 with 90% ee that could be converted into 16 by mesylation 15 followed by coupling with 1-naphthol. Opening of the epoxide 16 with isopropylamine leads to the formation of the target (S) -propanolol 17 .
Vanadium-Catalyzed Epoxidation
Few Studies are focused on chiral vanadium catalyzed the epoxidation of allylic alcohols. The epoxidation of homoallylic alcohol has been found to be successful (Scheme \(\PageIndex{8}\)).
Examples:
Niobium-Catalyzed Epoxidation
Chiral niobium-complexes catalyze the epoxidation of allylic alcohols in the presence of hydrogen peroxide (H 2 O 2 ) or urea hydrogen peroxide (UHP). From environmental and economic standpoint, this process is more attractive because it is atom economical and generates water as by-product. For example, [(μ-oxo){Nb(salan)} 2 ] 20 catalyzes the epoxidation of allylic alcohols in the presence of UHP at ambient conditions (Scheme \(\PageIndex{9}\)-\(\PageIndex{10}\)).
In this protocol, the μ-oxo dimer dissociates into a monomeric species that catalyzes the reaction (Scheme \(\PageIndex{11}\)). Moreover, monomeric Nb(salan) complexes prepared in situ from Nb(O i Pr) 5 and salan ligands followed by water treatment are found to catalyze the epoxidation better using aq. H 2 O 2 with enantioselectivity ranging from 83 to 95% ee. This is the first example of the enantioselective epoxidation of allylic alcohols using aq. H 2 O 2 as terminal oxidant.