Allyl alcohols asymmetric peroxidation

The known allylic alcohol 9 derived from protected dimethyl tartrate is exposed to Sharpless asymmetric epoxidation conditions with (-)-diethyl D-tartrate. The reaction yields exclusively the anti epoxide 10 in 77 % yield. In contrast to the above mentioned epoxidation of the ribose derived allylic alcohol, in this case epoxidation of 9 with MCPBA at 0 °C resulted in a 65 35 mixture of syn/anti diastereomers. The Sharpless epoxidation of primary and secondary allylic alcohols discovered in 1980 is a powerful reagent-controlled reaction.12 The use of titanium(IV) tetraisopropoxide as catalyst, tert-butylhydro-peroxide as oxidant, and an enantiopure dialkyl tartrate as chiral auxiliary accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity. If the reaction is kept absolutely dry, catalytic amounts of the dialkyl tartrate(titanium)(IV) complex are sufficient. 

The importance of this reaction also lies in the fact that asymmetric epoxidation of alkenes other than allylic alcohols is possible with this catalytic system (see Section 9.3.4). The third reaction relates to catalysts developed by Unilever for improved detergent action in the presence of hydrogen peroxide. The important point to note is that catalytic intermediates with metal-oxo groups play a pivotal role in all these reactions. 

Recent literature refers to the stereoselective and asymmetric epoxidation of allylic alcohols with organoaluminium peroxides. PhaSiOOH epoxidizes olefins with a stereoselectivity similar to that with peracid. Reports have been made of a-substituted hydroperoxides (acids, esters, ketones, amides, and nitriles) as effective epoxidizing reagents and the application of hexachloroacetone, tetrachloracetone, and hexafluoroacetone hydroperoxide, as well as the HaOa-Vilsmeier reagent system. ... 

AE reactions of simple olefins. The Sharpless AE reaction has been supplemented by other approaches to asymmetric epoxide synthesis the most evident goal being to obviate the need for an allylic alcohol. Attempts to carry out asymmetric epoxidation reactions on simple olefins have utilized transition-metal-containing catalysts such as porphyrins as well as stoichiometric chiral reagents (peroxides, dioxiranes, and oxaziridines). These approaches have been summarized [19]. 

The previous section described metal catalyzed epoxidation of allylic alcohols by alkyl hydroperoxides, and 193 was proposed as a model to predict the diastereoselectivity of these reactions,. In the cases presented, the reaction was diastereoselective but not enantioselective (sec. 1.4.F) and those epoxidation reactions generated racemic epoxides. To achieve asymmetric induction one must control both the relative orientation of the alkene relative to the peroxide and also the face of the substrate from which the electrophilic oxygen is delivered. Control of this type can be accomplished by providing a chiral ligand that will also coordinate to the metal catalyst, along with the peroxide and the alkene unit. There are two major asymmetric epoxidation reactions, one that can be applied only to allylic alcohols and is the prototype for asymmetric induction in these systems. The other is a procedure that can be applied to simple alkenes. Both procedures use a metal-catalyzed epoxidation that employs alkyl hydroperoxides, introduced in section 3.4.B.ii. 

When the previously cited transition structure 193 is applied to the asymmetric epoxidation of allylic alcohols, it must be modified to include binding of the peroxide, the allylic alcohol, and also the chiral tartrate. The metal in the new model is titanium rather than vanadium, and tetraisopropoxy titanium was found to react with 2 equivalents of diethyl tartrate to form a species such as 212, where OR = 0/-Pr and CO2R = CO2Et.3i7.3i8 The tartrate can bind to titanium from either the bottom or the top face.3i8 The nature of the... 

The Sharpless asymmetric epoxidation (sec. 3.4.D.i) exploits this chelation effect because its selectivity arises from coordination of the allylic alcohol to a titanium complex in the presence of a chiral agent. The most effective additive was a tartaric acid ester (tartrate), and its presence led to high enantioselectivity in the epoxidation.23 An example is the conversion of allylic alcohol 40 to epoxy-alcohol 41, in Miyashita s synthesis of the Cg-Ci5 segment of (-t-)-discodermolide.24 in this reaction, the tartrate, the alkenyl alcohol, and the peroxide bind to titanium and provide facial selectivity for the transfer of oxygen from the peroxide to the alkene. Binding of the allylic alcohol to the metal is important for delivery of the electrophilic oxygen and... 

Although the metal-catalysed epoxidation of olefins using peroxides has been known for a long time it is only this year that the first reports of asymmetric epoxidations have appeared. " The asymmetric epoxidation of allylic alcohols... 

A review describes the asymmetric epoxidation of allylic alcohols,369 another the role of metal oporphyrins in oxidation reactions.370 jhe TiiOPrMi, catalysed self-epoxidation of allylic peroxides proceeds via an intermolecular mechanism.371 Racemic allyl alcohols can be resolved by asymmetric epoxidation (eq.35).372 a Pd(II)/Mn02/benzoquinone system catalyses the oxidative ring-closure of 1,5-hexadienes (eq.36).373 propenyl phenols are oxidatively degraded to aryl aldehydes and MeCHO in the presence of Co Schiff-base catalysts.374 An Oppenauer-type oxidation with Cp2ZrH2/cyclohexanone converts primary alcohols selectively into aldehydes.375 co macrocycles catalyse the oxidation of aryl liydrazones to diazo compounds in high yields.376 similar Co complexes under CO oxidise primary amines to azo compounds.377 Arene Os complexes in the presence of base convert aldehydes and water slowly into carboxylic acids and H2.378... 

Sharpless asymmetric epoxidation (SAE) is the epoxidation of allylic alcohols into asymmetric epoxides in high chiral purity (high enantioselectiv-ity). Transition metal catalyst Ti(OPr ) with chiral additive, diethyl tartarate (DET), generates chiral catalyst (Scheme 9.40) which is responsible for the enantioselective outcome, while, tert-butyl hydroperoxide (TBHP) serves as an oxidant. Although, this eatalytic system holds disadvantage of low turnover number (TON) with potential safety coneems for using concentrated solutions of peroxides, the reaction has nevertheless been extensively used in pharmaceutical industry [76]. 

Mechanistic studies on the Sharpless asymmetric epoxidation, Eq. (8), where DIPT is diisopropyl tartrate, have been published.The rate law in CH2CI2 is first-order in substrate, catalyst, and oxidant, and shows an inverse second-order dependence on the inhibiting alcohol, in this case Pr OH. This is consistent with a mechanism in which both substrate and the peroxide displace Pr O to form a key intermediate in the reaction. [Differences in the selectivities of allylic and homoallylic alcohols in this reaction have been exploited to invert the expected enantioselectivity. ... 

---