Allylic alcohols Jacobsen

Ten years after Sharpless s discovery of the asymmetric epoxidation of allylic alcohols, Jacobsen and Katsuki independently reported asymmetric epoxidations of unfunctionalized olefins by use of chiral Mn-salen catalysts such as 9 (Scheme 9.3) [14, 15]. The reaction works best on (Z)-disubstituted alkenes, although several tri-and tetrasubstituted olefins have been successfully epoxidized [16]. The reaction often requires ligand optimization for each substrate for high enantioselectivity to be achieved. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

It should be added that many other groups have contributed to the predevelopments of these inventions and also to later developments. All four reactions find wide application in organic synthesis. The Sharpless epoxidation of allylic alcohols finds industrial application in Arco s synthesis of glycidol, the epoxidation product of allyl alcohol, and Upjohn s synthesis of disparlure (Figure 14.4), a sex pheromone for the gypsy moth. The synthesis of disparlure starts with a Ci3 allylic alcohol in which, after asymmetric epoxidation, the alcohol is replaced by the other carbon chain. Perhaps today the Jacobsen method can be used directly on a suitable Ci9 alkene, although the steric differences between both ends of the molecules are extremely small ... 

Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

The reaction was also successful for substituted salicylaldehydes. When Jacobsen came to develop his asymmetric epoxidation, which, unlike the Sharpless asymmetric epoxidation, works for simple alkenes and not just for allylic alcohols, he chose salens as his catalysts, partly because they could be made so easily from salicylaldehydes. For example ... 

Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis-amino-indanol for the synthesis of Crixivan, This process is very much the cornerstone of the whole synthesis. During the development of the first laboratory route into a route usable on a very large scale, many methods were tried and the final choice fell on this relatively new type of asymmetric epoxidation. The Sharpless asymmetric epoxidation works only for allylic alcohols (Chapter 45) and so is no good here. The Sharpless asymmetric dihydroxylation works less well on ris-alkenes than on trans-alkenes, The Jacobsen epoxidation works best on cis-alkenes. The catalyst is the Mn(III) complex easily made from a chiral diamine and an aromatic salicylaldehyde (a 2-hydroxybenzaldehyde). 

Katsuki T (1999) Epoxidation of allylic alcohols. In Jacobsen E, Pfaltz A, Yamamoto H (eds) Comprehensive asymmetric catalysis I—III. Springer, Berlin, Heidelberg, New York, p 621 f... 

The applicability of the Sharpless asymmetric epoxidation is however limited to functionalized alcohols, i.e. allylic alcohols (see Table 4.11). The best method for non-functionalized olefins is the Jacobsen-Kaksuki method. Only a few years after the key publication of Kochi and coworkers on salen-manganese complexes as catalysts for epoxidations, Jacobsen and Kaksuki independently described, in 1990, the use of chiral salen manganese (111) catalysts for the synthesis of optically active epoxides [276, 277] (Fig. 4.99). Epoxidations can be carried out using commercial bleach (NaOCl) or iodosylbenzene as terminal oxidants and as little as 0.5 mol% of catalyst. The active oxidant is an oxomanganese(V) species. 

Both chemical and enzymatic synthetic methods for the asymmetric oxidation of the carbon-carbon double bond have been developed [46], but the area of carbon-carbon double bond oxidations has been shaped by the breakthrough discovery of asymmetric epoxidation of allylic alcohols with the Katsuki-Sharpless method [47]. Catalytic asymmetric synthesis of epoxides from alkenes by Jacobsen... 

Asymmetric epoxidation The catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades. The non-racemic epoxides are prepared either by enantioselective oxidation of a prochiral carbon-carbon double bond or by enantioselective alkylidenation of a prochiral C=0 bond (e.g. via a ylide, carbene or the Darzen reaction). The Sharpless asymmetric epoxidation (SAE) requires allylic alcohols. The Jacobsen epoxidation (using manganese-salen complex and NaOCl) works well with ds-alkenes and dioxirane method is good for some trans-alkenes (see Chapter 1, section 1.5.3). 

Jacobsen, E. N., Wu, M. H. Epoxidation of alkenes other than allylic alcohols. Comprehensive Asymmetric Catalysis /-///1999, 2, 649-677. 

Equation 12.16 is an example of the Sharpless-Katsuki asymmetric epoxi-dation of allylic alcohols, which is catalyzed by a Ti complex bound to a chiral tartrate ligand.38 A Mn-salen39 complex serves as catalyst for asymmetric epoxi-dation (Jacobsen-Katsuki reaction) of a wide variety of unfunctionalized alkenes, shown in equation 12.17.40 0s04 complexed with chiral alkaloids, such as quinine derivatives (equation 12.18), catalyzes asymmetric 1,2-dihydroxylation of alkenes (known as the Sharpless asymmetric dihydroxylation).41 The key step of all these transformations is the transfer of metal-bound oxygen, either as a single atom or as a pair, to one face of the alkene. 

Another important application is the asymmetric epoxidation of cis cinnamate esters 210. They are poor substrates for AD and the allylic alcohols derived from them by reduction are poor substrates for AE. Jacobsen epoxidation gives epoxides in good yield (>90%) but not all is the d.v-cpoxide 211. There is some leakage to the trans epoxide 212 a typical ratio of 211 212 being 5 1. The cis epoxide is formed in excellent ee but the trans epoxide in only moderate ee. 

There are all sorts of problems with epoxidation by micro-organisms and in general laboratory chemists prefer to use the Sharpless or Jacobsen epoxidations described in chapter 25. The co-hydroxylase from Pseudomonas oleovorans does epoxidise aryl ethers of allylic alcohols with good selectivity and one product has been used in the synthesis of the (5-blocker metropolol.29 However the organism requires gaseous hydrocarbons as carbon sources and the epoxide products poison it. 

Epoxides are key chiral synthetic intermediates and their enantioselective preparation by oxidation of achiral alkenes is a key reaction in many synthetic strategies. Sharpless asymmetric epoxidation is suitable for most allylic alcohols [26, 27], but few general procedures exist for unfunctionalized olefins. Jacobsen s manganese salen-mediated epoxidation is suitable for and gives good selectivities with Z-olefins (85 to 90% ee) [28]. The enzyme chloroperoxidase... 

The Sharpless asymmetric epoxidation is reliable, but it works only for allylic alcohols. There is an alternative, however, which works with simple alkenes. The method was developed by Eric Jacobsen and employs a manganese catalyst with a chiral ligand built from a simple diamine. The diamine is not a natural compound and has to be made in enantiomeric form by resolution, but at least that means that both enantiomers are readily available. The diamine is condensed with a derivative of salicylaldehyde to make a bis-imine known as a salen. ... 

It s no surprise that when chemists from Bristol Myers Squibb needed the epoxide beiow, they turned to asymmetric dihydroxyiation rather than either of the epoxidation methods we have shown you. Sharpless epoxidation works only with allylic alcohols, and Jacobsen epoxidation performs poorly here, giving oniy 70-74% ee (mainly because the substrate is not a cis alkene). However, asymmetric dihydroxyiation saves the day with 98% ee and around 90% yield, and a variant of the reaction we have just shown you gives the epoxide, also in 90% yield—well worth the extra step. 

The main drawback in Sharpless epoxidation is that the substrate must bear a functional group to achieve the precoordination required for high enantioselec-tivity (as in the case of allyl alcohol). This restriction is not applicable to the epoxidation of alkyl- and aryl-substituted olefins with manganese complexes of chiral Schiffs bases as catalysts. Very high enantioselectivities can be obtained in these reactions (Jacobsen, 1993). The most widely used catalysts that give high enantioselectivity are those derived from the Schiff bases of chiral diamines such as [SiS] and [RR] 1,2-diphenylethylenediamine and [SS] and [RR] cyclohexyl-1,2-diamine. An example is the synthesis of cromakalim. 

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