Asymmetric dihydroxylations kinetic resolutions

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. 

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. ... 

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. 

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>. 

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]. 

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. 

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. 

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 the presence of a chiral amine such as quinine, Sharpless has demonstrated asymmetric catalysis for this dihydroxylation reaction that is also accelerated by this type of ligand. The oxidizing agent (oxygen donor) is then amine oxide. This system compares with Jacobsen s efficient hydrolytic kinetic resolution shown in section 4, but extension to the industrial scale is more problematic with the Sharpless system. 

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