Oxidation reactions, transition-metal asymmetric epoxidation

Hie first of Sharpless s reactions is an oxidation of alkenes by asymmetric epoxidation. You met vanadium as a transition-metal catalyst for epoxidation with r-butyl hydroperoxide in Chapter 33, and this new reaction makes use of titanium, as titanium tetraisopropoxide, Ti(OiPr)4, to do the same thing. Sharpless surmised that, by adding a chiral ligand to the titanium catalyst, he might be able to make the reaction asymmetric. The ligand that works best is diethyl tartrate, and the reaction shown below is just one of many that demonstrate that this is a remarkably good reaction. 

The hrst of Sharpless s reactions is an oxidation of alkenes by asymmetric epoxidation. You met vanadium as a transition-metal catalyst for epoxidation with f-butyl hydroperoxide in Chapter 33,... 

Transition-metal-catalysed epoxidations work only on aUylic alcohols, so there is one limitation to the method, but otherwise there are few restrictions on what can be epoxidized enantioselectively. When this reaction was discovered in 1981 it was by far the best asymmetric reaction known. Because of its importance, a lot of work went into discovering exactly how the reaction worked, and the scheme below shows what is believed to be the active complex, formed from two titanium atoms bridged by two tartrate ligands (shown in gold). Each titanium atom retains two of its isoprop oxide ligands, and is coordinated to one of the carbonyl groups of the tartrate ligand. The reaction works best if the titanium and tartrate are left to stir for a while so that these dimers can form cleanly. 

This chemical bond between the metal and the hydroxyl group of ahyl alcohol has an important effect on stereoselectivity. Asymmetric epoxidation is weU-known. The most stereoselective catalyst is Ti(OR) which is one of the early transition metal compounds and has no 0x0 group (28). Epoxidation of isopropylvinylcarbinol [4798-45-2] (1-isopropylaHyl alcohol) using a combined chiral catalyst of Ti(OR)4 and L-(+)-diethyl tartrate and (CH2)3COOH as the oxidant, stops at 50% conversion, and the erythro threo ratio of the product is 97 3. The reason for the reaction stopping at 50% conversion is that only one enantiomer can react and the unreacted enantiomer is recovered in optically pure form (28). 

Recent advances of the preparation of novel optically active organoselenimn compounds, mainly organic diselenides, and their application as chiral ligands to some transition metal-catalyzed reactions and also as procatalysts for asymmetric diethylzinc addition to aldehydes are reviewed. Recent results of catalytic reactions using some organoselenimn compounds such as aUylic oxidation of alkenes and its asymmetric version as well as epoxidation of alkenes are also summarized. 

The development of simple systems that allow for the asymmetric oxidation of allyl alcohols and simple alkenes to epoxides or 1,2-diols has had a great impact on synthetic methodology as it allows for the introduction of functionality with concurrent formation of one or two stereogenic centers. This functionality can then be used for subsequent reactions tliat usually fall into the substitution reaction class. Because these transition metal catalysts do not require the use of low temperatures to ensure high degrees of induction, they can be considered robust. However, the sometimes low catalyst turnover numbers and the synthesis of the substrate can still be crucial economic factors. Aspects of asymmetric oxidations are discussed in Chapter 12. 

Asymmetric manganese-salen-catalyzed epoxidation of unfunctionalized olefins was reported by Jacobsen et al. [74] in 1990, which allowed the enantioselective epoxidation of unfunctionalized olefins. In particular, the high enantioselectivities obtained for Jacobsen epoxidation on cis-olefins, nicely complement the Sharpless epoxidation and dihydroxylation protocols, which give reduced enantioselectivities for these substrates. The Sharpless and Jacobsen procedures are frequently used asymmetric oxidative reactions in API synthesis. More recently, organocatalytic procedures such as Shi epoxidations [75] were also employed to avoid toxic transition metal catalysts. 

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]. 

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