Epoxidation Of Alkenes Other Than Allylic Alcohols

The asymmetric epoxidation of unfunctionalised alkenes has received major attention and delivered considerable success through the development of metal-catalyzed oxo-transfer processes and the use of chiral manganese(III) salen com-plexes.4 The latter process requires the incorporation of a dissymmetric diimine bridge derived from a C2-symmetric 1,2-diamine and bulky substituents adjacent to the phenolate group. This is illustrated in the oxidation of cs-b-methylstyrene (Figure 11.3).5 The mechanistic hypothesis is that the bulky groups force approach of the alkene to an intermediate manganese oxo complex past the chiral bridge, thus inducing an enantioselective product outcome. While this hypothesis has served well in the development of successful catalysts, many problems remain, and there are indications that the hypothesis is rather simplistic. However, the delivery of very high enantioselectivity through relatively mild and inexpensive catalysts has encouraged further development and also industrial usage. There is also the possibility of using different oxidation conditions, such as sodium hypochlorite, isobutyraldehyde, and oxygen, peracids with an additional N-oxide catalyst, or iodosylbenzene.

A wide variety of salen complex analogs has been generated, and individual examples identified as being optimal for the asymmetric epoxidation of specific alkenes. Further examples are shown in Figure 11.4.6

There are now many examples of the industrial use of manganese(III) salen catalyzed asymmetric epoxidations. For example, the asymmetric epoxidation of a chromene derivative was central to the synthesis of the potassium channel activator BRL 55834 (Figure 11.5).7'8


Ph Me

Figure 11.3 Enantioselective epoxidation of alkenes by Mn salen complexes.

Ph trans

Figure 11.4 Enantioselective epoxidation of alkenes by Mn salen complexes.

The indole-7-carbaldehyde structural fragment is isosteric with the salicylalde-hyde structure, and consequently can replace it in the design and construction of new ligand systems. A wide range of substituted indole-7-carbaldehydes has been achieved by our group through the activation of C7 to formylation by the presence of methoxy groups at C4 and C6. This strategy provides an acidic NH instead of the acidic phenolic OH. Furthermore, a wide range of alkyl or aryl groups can be built in at C3, and C2 can also be substituted initially or be available for acid-catalyzed addition reactions later in the synthetic sequence (Figure 11.6).9 Benzimidazoles can be used similarly. Although these catalysts are highly reactive and effective, so far only relatively low enantioselectivity has been achieved.

Chiral porphyrin metal complex catalysts have also received much attention. In this situation, the flat, symmetrical porphyrin structure must be modified dramatically in order to incorporate dissymmetry. This has been achieved through strapping techniques.10'11 Some examples are shown in Figure 11.7.

BRL 55834

K channel activator

BRL 55834

Figure 11.5 Synthetic application of enantioselective epoxidation.

c/s-p-Methylstyrene c/s-p-Methylstyrene

Methylstyrene Structure

Me Me


Figure 11.6 The indole and benzimidazole strategy for enantioselective epoxidation.



1 double strap M = Mn-CI

Methylstyrene Structure

Figure 11.7 Chiral porphyrin complex catalysts.

2 single straps M = Fe-CI

Figure 11.7 Chiral porphyrin complex catalysts.

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