Enantioselective Oxidation of Alkenes

• Titanium-tartrate complexes e.g. Ti(Oi-Pr)4 2.t-butyl hydroperoxide (t-BuOOH) in excess • Used with chiral ligand L-(+)-DET or L-(+)-DIPT which are from the chiral pool • effect the catalytic, enantioselective epoxidation of allylic alcohols

• Electrophilic activation of the peroxide oxidant (t-BuOOH) by the Lewis acidic titanium centre • Lewis acid accepts electrons from O • Forms a highly strained intermediate which creates a chiral environment if there is a chiral ligand attached to Ti

• 2Ti(Oi-Pr)4 molecules added to 2 (+)-DET to produce a dimeric titanium species and 4-iPrOhH • can be represented as monomeric for simplification • One Titanium chelated by one DET • One Ester groups point up and on down

• t-BuOOH (epoxidising agent) is added • The OH displaces an Oi-Pr group and donates electron density to titanium

• The allylic alcohol substrate is added through displacement of the top apical i-Pr to create a chiral intermediate • Aligns allylic alcohol fragment in correct place for O of peroxy fragment to undergo transfer generating desired epoxide ring system • Results in high enantioselective facial selectivity

• Once epoxidation occured • Chiral epoxide fragment and t-BuOH are displaced by 2 i-PrOH to regenerate.

• Gives excellent enantioselectivities for a wide range of allylic alcohols • Z-configured allylic alcohols tend to give lower ers

• D-(-)-DET

• L-(+)-DET

• Double diastereocontrol • Gives very strong reagent control - catalyst control • Get matched or mismatched

• Directing effect of chiral catalyst overrules seelctivity of inherent diastereo substrate- opposite product

• CHP • It is less explosive

• Used in production of glycidol • Valuable enantiopure C3 building bloc,

• Combination of SAE followed by a regioselective epoxide reduction to prepare 1,3-diols • En route to antifungal agent amphotericin B

• Both enantiomers of allylic alcohol should be epoxidized from the same face but the rates of epoxidation are different • THe rate ratio kfast/kslow (selectivity factor, S) is typically high for SAE • So %ee of the unreacted alcohol is essentially 100% at 60% conversion • The conversion of the reaction is controlled by the limiting oxidant available and how much t-BuOOH is used is dictated by whether or not you want the enantiopure allylic alcohol or the enantiopure epoxy alcohol product

• Where R group is pointing towards the epoxidizing agent - steric hindrance

• 0.45 eq • Past 50% less reactive enantiomer starts to be produced - reduces selectivity • low conversion levels ideal- so low [t-BuOOH]

• 0.6 eq • Ensures all the more reactive alcohol has reacted so only left with less

• 50%

• Enantiotopic group discrimination • 100% • Effectively the same as two kinetic resolutions • The first deyymmetrises the compound • The second removes any trace of unwanted enantiomer • er of product increases with time

• One is pro-R group and one is a pro-S group • One of the groups is favoured for oxidation by DIPT so is fast reaction and produces the desired product • The other is slow and produces the undesired product • The undesired product then undergoes fast epoxidation favoured group is being epoxidized- • Therefore you get the desired single epoxide as undesired epoxide is epoxidized fast to produce a diepoxide

• Limited to allylic alcohols • Z-configured alkenes are poor substrates

• Jacobsen-Katsuki epoxidation • Chiral (salen) manganese (III) complexes typically using NaOCl as the oxidant

• Condensation of chiral diamine with 2 eq of substituted salicylaldehyde