Sharpless asymmetric epoxidation reaction

This is an example of the Sharpless asymmetric epoxidation reaction of allylic alcohols 7 one of the most versatile, reliable, and synthetically... 

What allylic alcohol and DET isomer are needed to make each chiral epoxide using a Sharpless asymmetric epoxidation reaction ... 

One enantiomer can be formed selectively from the reduction of a carbonyl group, provided a cbiral reducing ent is used. This strategy is identical to that employed in the Sharpless asymmetric epoxidation reaction (Section 12.15). A reduction that forms one enantiomer predominantly or exclusively is an enantioselective or asymmetric reduction. 

There is a strong tendency for 1 to undergo isomerization to isolaulimalide (2) even under mildly acidic conditions. Therefore it was decided to apply a Sharpless asymmetric epoxidation reaction to deoxylaulimalide 32 in the hope that the reagent control of this procedure would suffice to bring about the desired regioselectivity of... 

In conclusion, a Sharpless asymmetric epoxidation reaction may be used to achieve regioselectivity in a complex molecule containing two allylic alcohol moieties with opposite topicity. Thus, 32 could be alternatively converted into laulimalide (1) and its C-20 regioisomer simply by switching the chiral additive from +)- R,R)- to -)- S,S)-diisopropyl tartrate (DIPT). Biological tests have shown that the natural compound 1 is by far the most active one compared to other derivatives such as the C-20 regioisomer. 

Allyl epoxides are produced by the acclaimed Sharpless asymmetric epoxidation reaction [75], and are important intermediates and products. For example, an allyl epoxide is a vital part of the structure of amphidinolides, a series of unique macrolides isolated from dinoflagellates (Amphidinium sp.). Amphidinolide H (AmpH) is a potent cytotoxic 26-membered macrolide with potent cytotoxicity for several carcinoma cell lines [76]. An allyl epoxide is involved in the total synthesis of prostaglandin A2 with a cuprate reagent [77]. Allyl epoxides derived from Sharpless chemistry are a practical method for construction of polypropionate structures by Lewis acid-induced rearrangement [78,79]. Other allyl epoxides such as l,2-epoxy-3-methyl-3-butanol are useful organic intermediates for the production of a-hydroxyketones, which are used for the synthesis of various natural... 

N. N. Reed, T. J. Dickerson, G. E. Boldt, K. D. Janda, Enantioreversal in the Sharpless asymmetric epoxidation reaction controlled by the molecular weight of a covalently appended achiral polymer, J. Org. Chem. 70 (2005) 1728. 

Since the alcohol 39 is already known as a precursor for the wrong enantiomer of grandisol, an asymmetric synthesis of the right enantiomer would complete an efficient synthesis. The diene 58 is an ideal substrate for a Sharpless asymmetric epoxidation - reaction occurs only at the allylic alcohol (chapter 25). Two stage conversion of the OH into an iodide and treatment with zinc leads to an elimination 60 and the correct enantiomer of the tertiary alcohol 39 for conversion to grandisol.9... 

Scheme 8.5. Proposed mechanism for the Sharpless asymmetric epoxidation reaction of allylic alcohols, shown here for a simple tran -allylic alcohol. For the AE reaction, Ra = Rb = H. When one (or occasionally both) of these substituents are alkyl groups, the Scheme pertains to the kinetic resolution sequence described in the next section.

The bis(tetrahydrofuranyl) Annonaceous acetogenin ( + )-(15,16,19,20,23,24)-hexepiuva-ricin (74), has been synthesized utilizing a polyepoxide cascade reaction. The diiodide 70 is transformed into the bis-allylic alcohol 72, which is subsequently converted to a C2-sym-metric diepoxide utilizing the Sharpless asymmetric epoxidation reaction. Selective mono-tosylation of the primary hydroxyl groups served to desymmetrize the system. An acid-catalyzed deketalization followed by simultaneous epoxide opening affords the erythro trans threo trans erythro-conf gmdXion present in the tosylate 73. Transformation of 73 to the desired 74 completes the synthesis [32] (Scheme 17). 

For allylic alcohols, use the Sharpless asymmetric epoxidation reaction. Reagents are t-BuOOH, Ti(Oi-Pr)4 and (-l-)-diethyl (or di-isopropyl) tartrate. Note that the (-1-)-enantiomer of the ligand is required for the formation of the epoxide 6 (place the alcohol in the lower right using the model given in Scheme 5.55). 

Despite the complexity of the active catalyst, the sense of asymmetric induction in Sharpless asymmetric epoxidation reactions can be rehably predicted using the model shown in Figure 4.2. In order for the model to predict the stereochemical outcome correctly, only two points need to be remembered. The allyhc hydroxy group resides in the bottom right corner and D-(-)-diethyl tartrate (which has the (S,S)-configuration) attacks from above the plane. 

A l-0-silyl-2,5-cyclohexylidene derivative has been transformed into condur-itol E and 2-deoxy-a//o-inositol in which chirality was introduced using a Sharpless asymmetric epoxidation reaction, and 1,4- and 1,3-cyclohexadienes have been bis-epoxidized and the epoxide rings cleaved with azide to afford di-azido diol compounds which were asymmetrized enzymatically. ... 

Scheme 7, Use of the Sharpless asymmetric epoxidation reaction to achieve the synthesis of hydroxy epoxide 30 through kinetically controlled enantiomeric enrichment.

The Sharpless asymmetric epoxidation reaction has been utilized widely in total syntheses. Nicolaou investigated the combination of a Sharpless asymmetric epoxidation with a regioselective reduction of the resulting epoxide in an iterative manner as a general means to synthesize 1,3-skipped polyols [80]. The strategy was put into practice in the total synthesis of the antifungal agent amphotericin B (64, Scheme 9.7) [81]. 

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