Resolutions asymmetric dihydroxylations

Kinetic resolution of racemic allylic acetates has been accomplished via asymmetric dihydroxylation (p. 1051), and 2-oxoimidazolidine-4-carboxy-lates have been developed as new chiral auxiliaries for the kinetic resolution of amines. Reactions catalyzed by enzymes can be utilized for this kind of resolution. ... 

Until recently, syntheses of enantiopure r/v-aminoindanols relied either on starting materials from the chiral pool or on chemical or enzymatic resolution of racemic intermediates.7 36 1 Advances in catalytic asymmetric epoxidation (AE) and asymmetric dihydroxylation (AD) of prochiral olefins42-48 enabled the development of truly practical asymmetric syntheses of cis-1 -amino-2-indanols (see Chapter 9).49-54... 

Sharpless catalytic asymmetric dihydroxylation of 2-vinylfuran followed by treatment of the diol product with NBS, and subsequent Jones oxidation and Luche reduction provided a highly functionalized a,(1-unsaturated y-lactone in 70% yield overall giving a key intermediate in the synthesis of phomopsolide C <02TL8195>. Similar procedures were adopted by the same authors to synthesize 2-deoxy and 2,3-dideoxyhexoses <02OL1771>. As depicted below, Sharpless kinetic resolution was also used to prepare a pyranone from a furfuryl alcohol in 38% yield, which served as the intermediate in the synthesis of (+)-isoaltholactone <02T6799>. 

Both resolution and Sharpless asymmetric dihydroxylation were successful in the synthesis of Crixivan but the best method is one v e shall keep till later. Only one stereogenic centre remains, and its stereoselective formation turns out to be the most remarkable reaction of the whole synthesis. The centre is the one created in the planned enolate alkylation step,... 

There are many possible answers here. What we had in mind was some sort of asymmetric Die Alder reaction for the first (pp. 1228-31), an asymmetric aldol reaction for the second or e i opening an epoxide made by the Sharpless epoxidation (pp. 1239-41), asymmetric dihydroxylat on an -alkene for the third (pp. 1241-3), and perhaps asymmetric dihydroxylation on a Z-alker for the fourth. Of course, you might have used resolution or catalytic hydrogenation, or the ch pool, or any other strategy you could devise. 

R,9Z)-oetadec- 9-en-4-olide Currant stem girdler (Janus integer) Fs Sharpless asymmetric dihydroxylation and Jacobsen hydrolytic kinetic resolution (HKRL [204]... 

Asymmetric dihydroxylation of the alkene 18 could be used to access either enantiomer by a kinetic resolution (Scheme 3.16). In this approach, the desired alkene is the unreacted material [316]. 

We will see Sharpless epoxidation reactions in the Double Methods section towards the end of the chapter. Interestingly, Sharpless other famous asymmetric method - dihydroxylation - has not found widespread use in kinetic resolution. This is probably because the AD is just too powerful or, to be anthropomorphic, too wilful. In other words, it is not sensitive to the chirality of the substrate and charges ahead and reacts with both enantiomers. That is not to say there are not examples of kinetic resolution with dihydroxylation,19 but they are more rare. However, the dihydroxylation is even more useful and much more general than the kinetic resolution of allylic alcohols by asymmetric epoxidation and was discussed in Chapter 25. A slightly complicated case of kinetic resolution of alcohols by asymmetric dihydroxylation is in the Double Methods section. 

Asymmetric addition of an organo-zinc to an aldehyde Synthesis by asymmetric dihydroxylation of a non-conjugated diene A Disappointment and a Resolution Part IV - Metalloproteinase Inhibitors... 

Syntheses of relatively simple chiral drugs on an industrial scale are the domain of catalytic or enzymatic methods. In the case of the calcium antagonist diltiazem [113] Sharpless asymmetric dihydroxylation (AD-reaction) is employed which works particularly efficiently for cinnamic acid derivatives such as 48-1. In fact diol 48-2 is obtained with good optical enrichment and is then converted into the target compound via 6 routine steps. Alternatively diltiazem is prepared via classical optical resolution or via enzymatic kinetic resolution of suitable intermediates [113]. 

Xing, X. Zhao, Y. Xu, C. Zhao, X. Wang, D. Z. Electronic Helix Theory-guided Rational Design of Kinetic Resolutions by Means of the Sharpless Asymmetric Dihydroxylation Reactions. Tetrahedron 2012,68,7288-7294. 

In pharmaceutical indusby, C-O bond formation is a very important reaction. Classical resolution is a very powerful and simple method for obtaining chiral alcohol/epoxide molecules, while, resolution is still being used along with enantioselective synthetic methods. Numerous asymmetric reactions are frequently employed for C-O bond formation in large-scale API synthesis. In 1980, Sharpless et al. [72] reported asymmetric titanimn tartarate-catalyzed epoxidation of allylic alcohols, which was followed by the discovery of many asymmetric catalytic reactions. Yet, another important reaction on the asymmetric dihydroxylation was also reported by Sharpless et al. in 1988 [73]. 

It was later found that the chiral amine can be used as the tertiary amine generating the N-oxide required for reoxidation of Os . Thus, a simplified procedure for osmium-catalyzed asymmetric dihydroxylation of alkenes by H2O2 was developed in which the tertiary amine NMM is omitted [108]. A robust version of this reaction, where the flavin 19 has been replaced by MeReOs (MTO), was recently reported [109], The chiral ligand has a dual role in these reactions it acts as a chiral inductor as well as an oxotransfer mediator (Scheme 7.13). The amine oxide of the chiral amine ligand was isolated and characterized by high resolution mass spectrometry [109]. 

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

The first total synthesis of racemic camptothecin was reported by Stork and Schultz as early as 1971. A number of total syntheses followed, many of which were also of racemic material 7 Enan-tiomcrically pure natural product has been prepared by the method of kinetic resolution through use of chiral auxiliaries,9 and by Sharpies dihydroxylation,J0 an example of a catalytic asymmetric route. 

Conclusion. The C2 symmetry of (R,R)- and (S,S)-1,2-diaminocyclohexane, readily available from the racemic compound by resolution, has served as a versatile chiral motif in the design of topologically unique stereodifferentiating reagents such as the phosphonamide anions described here. Several other applications of these reagents via anion chemistry, or simply based on the exploitation of other effects offered by their structures and heteroatom functionality, can be explored (catalytic processes, chiral ligands, etc.). The lYfY-disubstituted 1,2-diaminocyclohexane motif has also been remarkably versatile in other asymmetric processes such as the dihydroxylation of alkenes, and a variety of other C-C bond-forming reactions. ... 

Several enantioselective approaches to vitamin E (1), based on resolution of the products, the use of enantiopure natural building blocks, auxiliary controlled reactions and asymmetric oxidations have been described. In addition, a palladium-catalyzed asymmetric allylic alkylation reaction to build up the chiral chroman framework has been employed by Trost. Tietze and coworkers have developed asymmetric syntheses of the chiral chroman moiety using either the selective ally-lation of an alkyl methyl ketone or a Sharpless dihydroxylation as the key step. However, none of these methods is efficient enough for an industrial approach. ... 

Before the dihydroxylation reaction burst onto the asymmetric scene, asymmetric epoxidation and associated kinetic resolutions were possibly the most popular methods of producing single enantiomers simply because they worked so well. The epoxidation could, for example, be used reliably in undergraduate laboratories. 

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