Acetals asymmetric epoxidation

A typical manganese-salen complex (27)[89] is capable of catalysing the asymmetric epoxidation of (Z)-alkenes (Scheme 18) using sodium hypochlorite (NaOCl) as the principle oxidant. Cyclic alkenes and a, (3-unsaturated esters are also excellent starting materials for example indene may be transformed into the corresponding epoxide (28) with good enantiomeric excess1901. The epoxidation of such alkenes can be improved by the addition of ammonium acetate to the catalyst system 911. 

The effect of structural variation and the use of different caboxylate salts as cocatalysts was investigated by Pietikainen . The epoxidation reactions were performed with the chiral Mn(III)-salen complexes 173 depicted in Scheme 93 using H2O2 or urea hydrogen peroxide as oxidants and unfunctionalized alkenes as substrates. With several soluble carboxylate salts as additives, like ammonium acetate, ammonium formate, sodium acetate and sodium benzoate, good yields (62-73%) and moderate enantioselectivities (ee 61-69%) were obtained in the asymmetric epoxidation of 1,2-dihydronaphthalene. The results were better than with Ai-heterocycles like Ai-methylimidazole, ferf-butylpyridine. 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

We recently reported our results on the asymmetric epoxidation of trans-disubstituted and trisubstituted alkenes, using Oxone as oxidant, catalyzed by readily available arabinose-derived 4-uloses containing tunable steric blockers that control the enantioselectivity of the epoxidation.Ulose (3), containing a 2, 3 -diisobutyl acetal unit, was the most efficient catalyst and displayed good enantioselectivity. 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

The precatalyst used in these water-based kinetic resolution reactions is the cobalt Schiff-base complex 9.40. Its structural similarity to the asymmetric epoxidation catalysts 9.38A and 9.38B is to be noted. In the actual catalytic system 9.40 is activated with small amounts of acetic acid and air to give a cobalt(III) complex where CH3C02 and H20 are additional ligands. The mechanistic details of this reaction are as yet unknown. 

C4C1im][BF4] [C imKPFs] Mn(salen) complex NaOCl Asymmetric epoxidation CH2C12 or ethyl acetate as co-solvent reaction proceeds faster in the ionic liquid relative to conventional solvents product extracted with hexane catalyst was recycled 8 times, activity and selectivity decrease steadily. [50]... 

In a series of papers, the application of titanium alkoxide catalysts to the synthesis of sugars has been described. Asymmetric epoxidation and kinetic resolution of (48) afforded (+)-(49) (27% >95%e.e.) and (—)-(48) (33% 72%e.e.). The ring-opening reactions of the chiral epoxides that are produced, for example, from cis- and from trans- 50) provide new routes to saccharides. The reagents also find use in the synthesis of pheromones e.g., (+)-disparlure and (+)-2,6-dimethylhepta-l,5-dien-3-ol acetate via the epoxide (52), which was obtained from the dienol (51) by using D-(—)-... 

Manganese has a rich history within the field of organic synthesis (363, 364). For example, the permanganate anion has long been used as an oxidant to produce a variety of products (363). Manganese111 acetate also has been extensive explored over the years for the initiation of free radical reactions that lead to carbon-carbon bond formation. These topics have been reviewed and will not be presented further here (363, 364). Manganese chemistry, however, has made an impact in other areas as well, notably the asymmetric epoxidation of alkenes. 

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