Sharpless AD reaction

A wide range of alkenes undergo the Sharpless AD reaction and the stereochemistry of the product diols can be predicted with a high degree of certainty, in most cases, through a simple mnemonic device (Figure 1.2). Thus the DHQD derivatives supplied with the oxidant have become known as AD-mix (3 while the DHQ derivatives (with oxidant) comprise AD-mix a[81]. Chosen from the... 

An alternative synthetic method for preparing chiral l,2-epoxy-3-alkanol tosylates using Sharpless AD reaction as the key step has been reported and was used in the total synthesis of two insect pheromones namely,... 

Although CrCl2 and CrS04 are the two low-valent chromiutn(II) salts typically used5 to reduce ynones to trans enones, both reagents failed to give satisfactory yields of product when applied to 7. However, when [Cr(OAc)2 H20]2 was employed for this reduction (Scheme 7.4), a 60% yield of product was obtained. Double O-desilylation was next performed to access diol 6, the substrate needed for the Sharpless AD reaction.3... 

This is the Sharpless asymmetric dihydroxylation reaction 3 one of the most powerful and versatile catalytic asymmetric reactions ever to be discovered. The Sharpless AD reaction owes its success to the presence of... 

Sharpless AD reaction is extremely useful and efficient for the asymmetric dihydroxylation of alkenes. 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

Recommended ligands for different classes ofalkenes Applications of the Sharpless AD Reaction... 

Scheme 8.16. The two catalytic cycles proposed for the Sharpless AD reaction [72].

Scheme 8.17. The predicted enantioselectivity of Sharpless AD reactions using DHQD or DHQ ligands. This model is used by orienting the substrate so that the large (often aromatic), medium, and small substituents match up best with the Rl, Rm. Rs positions. Application of this model to some alkenes will inevitably result in some compromises in placing the groups.

Figure 8.6. One view of a proposed intermediate in the Sharpless AD reaction of the (DHQD)2PHAL-derived osmium species reacting with styrene [80].

Scheme 8.21. Use of the Sharpless AD reaction in the synthesis of an enantiomerically enriched (98.5% ee) biaryl diol [93].

The dicarbonyl compoimd 51 was oxidized to the anhydride 52, which subsequently reacted with primary or secondary amines to form a-amino acids, a-amino amides and dipeptides 53 (Scheme 14) [48]. 3-Hydroxy j8-lactams obtained from imines derived from carbohydrates [49,50] or prepared via the Sharpless AD reaction [51-53] were directly oxidized to anhydrides by treatment with NaOCl and TEMPO. Anhydrides 54-56 were used for the synthesis of compounds related to the family of polyoxins represented by 57 (Scheme 15) [49-53]. 

Hydroxy lactones are formed from p,y- and 7,8-unsaturated esters under the Sharpless AD reaction conditions, where the diol closes selectively to provide 7 -lactones. The enantiomeric excess can be excellent, as with the unsaturated ester (5.27), which produces the 7 -lactone (5.28). 

Cyclic enol ethers are also good substrates for the Sharpless AD reaction with ee being dependant on the chain length of the enol ether side chain. Thus, while the pentyl enol ether (5.32) is converted into a-hydroxyketone (5.36) with 94% ee, the corresponding methyl enol ether is oxidised with only 83% ee. 

Z)-disubstituted-alkenes are not usually good substrates for the Sharpless AD reaction, and although alternative ligands have been used, enantioselectivities are moderate, with only a few exceptions. 

Even three decades after its initial discovery, the Sharpless asymmetric dihydrox-ylation (Sharpless AD reaction) of alkenes still stands out as the most versatile alkene difunctionalization process [75] (Scheme 16.27). This reaction converts all kinds of alkenes into the corresponding vicinal diols with very high to excellent enantiomeric excess. Mechanistic discussion on this transformation has been extensive. At present, consensus centers on a concerted [3+2] mechanism with the simultaneous formation of two carbon-oxygen bonds [76]. 

Han, P Wang, R. Wang, D. Z. Electronic Polarizability-based Stereochemical Model for Sharpless AD Reactions. Tetrahedron 2011,67,8873-8878. 

As a starting point for a discussion of trifunctional catalysis. Scheme 14.5 provides a general overview of the Sharpless AD reaction. 

Scheme 14.5 General scheme of the Sharpless AD reaction, Os-mediated dihydroxylation of olefins...

---