Alkenes, epoxidation stereochemistry

Allylic alcohols represent a small fraction of the total population of alkenes found in organic molecules. Asymmetric epoxidation of allylic alcohols therefore taps only a small portion of the synthetic potential inherent in a completely general asymmetric epoxidation of isolated (nonfunctionalized) alkenes. A partial solution to this problem now exists. The recent development of a catalytic asymmetric process for the dihydroxylation of aUcenes provides an indirect route to epoxides or epoxide-like functionalization of alkenes. The stereochemistry of the process, the scope of enantioselectivity and chemical yield and a summary of key chemical transformations are presented in this section. Since this roach to alkene functionalization is at an early stage of development, the results sununarized here are certain to benefit from extensions and improvements as research in this area progresses. 

A hindered Hthium amide such as lithium 2,2,6,6-tetramethylpiperidide (LTMP) has proved to be effective in triggering a direct intramolecular cyclopropanation of the unsaturated terminal epoxide 31 to the tricycHc alcohol 32 (2010JOC2157). This strategy has been used successfully in a concise synthesis of (—)-cubelol (33) from (—)-menthone. Similarly, the naturally occurring (—)-10-epicubelol (34) can be prepared from (+)-menthone. Interestingly, whatever is the stereochemistry of the tethered alkene, the facial selectivity of cyclopropanation is controlled solely by the epoxide stereochemistry (Scheme 8). 

For an alkene that shows ds,trans isomerism, epoxidation is also stereospecific the stereochemistry of the product depends on the stereochemistry of the starting alkene. Epoxidation of ds-2-butene, for example, yields only the meso compound cis-2,3-dimethyloxirane, and epoxidation of frans-2-butene yields only the enantiomers of... 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

In the envisaged titanium oxo complex, the Ti atom is side-bound to the peroxy moiety (02H), consistent with all the spectroscopic results mentioned in Section III in Scheme 27, between the two O atoms that are side-bound to Ti4+, the O atom attached to both the Ti and H atoms is expected to be more electrophilic than the O atom attached to only the Ti atom and is likely to be the site of nucleophilic attack by the alkene double bond. The formation of the Ti-OH group (and not the titanyl, Ti=0, as proposed by Khouw et al. (221)) after the epoxidation and its subsequent condensation with Si-OH to regenerate the Ti-O-Si links had been observed (Section III.B) by FTIR spectroscopy by Lin and Frei (133). Because this is a concerted heterolytic cleavage of the 0-0 bond, high epoxide selectivity and retention of stereochemistry may be expected, as indeed has been observed experimentally (204). 

The analogous process involving allylic epoxides is more complex, as issues such as the stereochemistry of substituents on the ring and on the alkene play major roles in determining the course of the reaction [38]. Addition of the Schwartz reagent to the alkene only occurs when an unsubstituted vinyl moiety is present and, in the absence of a Lewis acid, intramolecular attack in an anti fashion leads to cyclopropane formation as the major pathway (Scheme 4.10). cis-Epoxides 13 afford cis-cyclopropyl carbinols, while trans-oxiranes 14 give mixtures of anti-trans and anti-cis isomers. The product of (S-elimi-... 

NBS is a source of Br+. It reacts with alkenes to give bromonium ions. Then both C-Br bonds need to be replaced by C-0 bonds by single inversions, since the trans stereochemistry of the double bond is retained in the epoxide. Under these acidic conditions the bromonium ion is opened intramolecularly by the acid carbonyl O, with inversion at one center loss of H+ gives a bromolactone. 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

The epoxidation of alkenes is an especially important process because of its capacity to introduce useful functionalization that is also capable of establishing stereochemistry at two vicinal carbon atoms. Allylic alcohols provide an excellent... 

In contrast to reactions with vinyl epoxides and palladium catalysts, the reactions with rhodium retain the stereochemistry of the alkene fragment during the reaction [20]. This is illustrated by the reactions of trans-37a/h and cis-37a/b, which give only one product possessing the same olefin geometry as the starting epoxides (Eqs. 4 and 5). The retention of olefin stereochemisty has also been documented in allylic functionalizations with iridium catalysts, indicating that similar modes of action may be present [21, 22]. 

The stereochemistry of the alkene is retained in the epoxide. The reaction is a stereospecific cis addition, (c) The cis- and frans-alkenes would give the same carbocation, which would go on to give the same product(s). The mechanism probably involves a one-step transfer of the O to the double bond, without intermediates. 

The rotation about the carbon-carbon bond in intermediate 30 is fast compared to cyclization. As a result isomeric alkenes are transformed to oxiranes of the same, predominantly trans stereochemistry. A practical process for the epoxidation of a wide range of alkenes was described in the presence of biacetyl as sensitizer to yield epoxides in about 90% yield.268... 

Stereoselective deoxygenation of epoxides. The ate complex [Bu3SnAl-(CH3)3] Li+ (1) formed from Bu3SnLi and A1(CH3)3 converts epoxides to alkenes with overall retention of stereochemistry. The results can be explained by inversion in the epoxide cleavage and antf-elimination of the Bu3Sn and O A1(CH3)3 groups. Example ... 

By-products in the reactions in Table 3 are mainly cleavage products (carbonyls) An interesting by-product is found in the oxidation of styrene, as phenyl acetate is produced. It has been found that phenyl acetate is formed via oxidation of either styrene oxide or acetophenone. Nearly the same yield and stereochemical mixture of the epoxides, as in Table 3, can be obtained by oxidation with Ag202. It appears from Table 3 that the epoxidation of alkenes catalyzed by discrete silver complexes also takes place without maintaining the stereochemistry of the alkene, as in the silver-surface catalyzed reaction. 

Acid-catalyzed hydrolysis of the epoxide yields a diol its stereochemistry corresponds to net anti hydroxylation of the double bond of the original alkene. 

Epoxides give rise to many 1,2-difunctionalised compounds such as 48 with control over stereochemistry. Reactions of the epoxide 49 from 44 give the anti stereochemistry in 48 in contrast to the syn stereochemistry in 43. Other compounds made from alkenes include 1,2-bromides and bromohydrins from reaction with bromine alone or bromine and water. 

The anti-cancer compound coriolin 23 has three fused five-membered rings and two epoxides. Notice that the 3/5 and both 5/5 ring fusions are cis. There have been many syntheses of coriolin, most using stereochemistry from folded precursors.7 We shall feature a couple of examples. Matsomoto s synthesis involves the hydroboration of alkene 24. The addition of borane is cis 25 and the boron is replaced by OH with retention of configuration to give 26. The hydroboration occurred on the outside of the molecule, on the same face as the ring junction hydrogens.8... 

In this section, we review the development of organocatalytic ylide-based epox-idation methods which allow a one-step route from carbonyl compounds, and therefore compete with the more traditional two-step approach of olefination followed by epoxidation of the resulting alkene (see Scheme 10.1) [13]. Indeed, ylide-based methodologies side-step the construction of a C=C double bond and achieve the whole transformation in one step thus, they are potentially more atom-efficient (see Scheme 10.1). However, there are greater challenges as both the absolute and relative stereochemistries must be controlled in one step [14-22]. 

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