Alkenes, dihydroxylation enantioselectivity

The AA reaction is closely related to the asymmetric dihydroxylation (AD). Alkenes are enantioselectively converted to protected 3-aminoalcohols (Scheme 1) by syn-addition of osmium salts under the influence of the chirr 1 bis-Cinchona ligands known from the AD process (see Chap. 20.1). As for the AD reaction, a cooxidant is needed to regenerate the active osmium species. But in the AA process the cooxidant also functions as the nitrogen source. Since two different heteroatoms are transferred to the double bond, regioselectivity becomes an important selectivity issue in addition to enantioselectivity. Moreover, chemoselectivity has to be addressed due to the possible formation of the... 

Although a large number of asymmetric catalytic reactions with impressive catalytic activities and enantioselectivities have been reported, the mechanistic details at a molecular level have been firmly established for only a few. Asymmetric isomerization, hydrogenation, epoxidation, and alkene dihydroxylation are some of the reactions where the proposed catalytic cycles could be backed with kinetic, spectroscopic, and other evidence. In all these systems kinetic factors are responsible for the observed enantioselectivities. In other words, the rate of formation of one of the enantiomers of the organic product is much faster than that of its mirror image. 

Quite recently it was reported that in addition to hydrogen peroxide, periodate or hexacyanoferrat(III), molecular oxygen21,31-34 can be used to reoxidize these metal-oxo compounds. New chiral centers in the products can be created with high enantioselectivity in the dihydroxylation reactions of prochiral alkenes. The development of the catalytic asymmetric version of the alkene dihydroxylation was recognized by Sharpless receipt of the 2001 Nobel prize in Chemistry. 

As summarized in Scheme 2.8, these reactions provide access to three different overall stereochemical outcomes for alkene dihydroxylation, syn addition, anti addition, or stereorandom addition, depending on the reaction mechanism. In Section 2.5.4 we will discuss enantioselective catalyst for alkene dihydroxytation. These reactions provide further means of controlling the stereochemistry of the reaction. 

Structures 2.51 and 2.52 show ligands used in enantioselective epoxidation of allylic alcohols and asymmetric alkene dihydroxylation (ADH) reactions, respectively (see Section 8.5). 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

When asymmetric epoxidation of a diene is not feasible, an indirect route based on asymmetric dihydroxylation can be employed. The alkene is converted into the corresponding syn-diol with high enantioselectivity, and the diol is subsequently transformed into the corresponding trans-epoxide in a high-yielding one-pot procedure (Scheme 9.5) [20]. No cpirricrizalion occurs, and the procedure has successfully been applied to natural product syntheses when direct epoxidation strategies have failed [21]. Alternative methods for conversion of vicinal diols into epoxides have also been reported [22, 23]. 

Scheme 12.7. Enantioselective Osmium-Catalyzed Dihydroxylation of Alkenes...

Asymmetric osmylation of alkenes.3 In the presence of 1 equiv. each of 1 and 0s04, alkenes undergo highly enantioselective ris-dihydroxylation. Highest enantiofacial selectivity (90-99%) is shown in osmylation of trans-di- and trisub-... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

Table 4. Calculated and experimental enantioselectivities in the asymmetric dihydroxylation with different alkenes and bases (adapted from Ref. 28).

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

Scheme 55 Electrochemical enantioselective Sharpless dihydroxylation of alkenes.

Application of computaional methods to the enantioselective dihydroxylations of alkenes by osmium complexes have been reviewed with a special focus on methods used to study the origin of high enantioselectivity. The use of a vast number of computational techniques such as QM, MM, Q2MM, QM/MM, molecular dynamics, and genetic algorithms has been enumerated.98... 

Osmium-catalysed dihydroxylation of olefins is a powerful route towards enantioselective introduction of chiral centers into organic substrates [82]. Its importance is remarkable because of its common use in organic and natural product synthesis, due to its ability to introduce two vicinal functional groups into hydrocarbons with no functional groups [83]. Prof. Sharpless received the 2001 Nobel Prize in chemistry for his development of asymmetric catalytic oxidation reactions of alkenes, including his outstanding achievements in the osmium asymmetric dihydroxylation of olefins. 

We have recently broadened those investigations to study the origin of the enantioselectivity in the dihydroxylation of terminal aliphatic n-alkenes. The dihydroxylation of the series from propene to 1-decene was studied by means of the IMOMM method [97]. Experimental studies on propene, 1-butene, 1-pentene, 1-hexene and 1-decene showed that the reaction was enantioselec-tive in all cases, leading to the R product. Moreover, the results show a dependence of the enantioselectivity on the chain length it sharply increases from propene to 1-pentene, and after that the enantioselectivity remains practically constant for 1-hexene and 1-decene. The explanation for this dependence of the enantioselectivity with the chain length remained elusive. On the other hand, the -stacking interactions that were found to be critical for styrene cannot be responsible for the observed enantioselectivity for these terminal aliphatic n-alkenes because they do not have aromatic rings. 

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