Oxidation reactions diastereoselectivity

The enol ether double bond contained within the ds-fused dioxa-bicyclo[3.2.0]heptene photoadducts can also be oxidized, in a completely diastereoselective fashion, with mCPBA. Treatment of intermediate XXII, derived in one step from a Patemo-Buchi reaction between 3,4-dimethylfuran and benzaldehyde, with mCPBA results in the formation of intermediate XXIII. Once again, consecutive photocycloaddition and oxidation reactions furnish a highly oxygenated system that possesses five contiguous stereocenters, one of which is quaternary. Intermediate XXIII is particularly interesting because its constitution and its relative stereochemical relationships bear close homology to a portion of a natural product known as asteltoxin. 

Asymmetric induction also occurs during osmium tetroxide mediated dihydroxylation of olefinic molecules containing a stereogenic center, especially if this center is near the double bond. In these reactions, the chiral framework of the molecule serves to induce the diastereoselectivity of the oxidation. These diastereoselective reactions are achieved with either stoichiometric or catalytic quantities of osmium tetroxide. The possibility exists for pairing or matching this diastereoselectivity with the face selectivity of asymmetric dihydroxylation to achieve enhanced or double diastereoselectivity [25], as discussed further later in the chapter. 

The most smdied O-bonded transition metal enolates are titanium enolates . The reason for their success has beeu recognized in the fact that titanium enolates show an enhanced stereochemical control in C—C bond-forming reactions over simple lithium enolates and the possibility of incorporating chiral ligands at the titanium centre, a possibility which has lead to enantioselective aldol reactions with excellent enantiomeric excess. Moreover, titanium euolates have been used in oxidation reactions with remarkable diastereoselectivity. 

If the optically active organoselenium compounds can be used for Tomoda s or Tiecco s catalytic system using diselenide and persulfate (see Sect. 4.1), a catalytic asymmetric oxidation reaction should be possible. The enantioselectivity of the produced allylic compounds may depend on the stereoselectivity of the oxyselenenylation step of chiral selenium electrophiles with prochiral alkenes. Several groups have reported diastereoselective oxyselenenylation using a variety of chiral diselenides in moderate to high diastereoselectivity [5 f, g, i, 25]. The detailed results are reviewed in Chap. 2. 

An important clue as to how this could be done came from work done by Henbest and coworkers [2]. This group compared the diastereoselectivity of peracid oxidation reactions of 3-hydroxy and 3-acyloxycyclohex-2-enes (Scheme 8.2). When the alcohol was capped by an acetate group, the trans addition product predominated. Better selectivity was later obtained by placing a larger trimethylsilyl group on the allylic alcohol [3]. In both cases, the source of the selectivity could be ascribed to the approach of the reagent from the least hindered side of the molecule anti to OR) put another way, the approach from one face was slowed relative to the other (Scheme 8.2a). 

This multi-step scheme illustrates the synthetic efforts that have been invested in the construction of homochiral biaryl 15 without loss of enantiomeric purity. It covers many significant modem synthetic reactions diastereoselective cyanation, of the carbonyl group in (-i-)-9 in step i, promoted by a fi-orientation of the carbonyl oxygen to the orffio-substituent as the result of a stereoelectronic effect [52] oxidative removal of the Cr(CO)3 group in 13 (step vi) and stereoselective azidation with inversion of the configuration (step vii). For more details, the interested reader should consult the cited literature. 

Initial attempts to convert the 2,3-tra J-2,6-tran5-tetrahydropyran aldehyde 2.197a to the epoxide 2.198 through asymmetric allylation and subsequent epoxidation were made (Scheme 2.41). Towards this end, aldehyde 2.198 was transformed to the homoaUyl alcohol 2.201 via Brown asymmetric allylation [95], was in turn exposed to a variety of epoxidation conditions, including Sharpless asymmetric epoxidation [146] as well as achiral reagents such as VO(acac)2/t-BuOOH [147, 148] and m-CPBA. Unfortunately, aU attempts were not effective for the installation of the epoxide. Instead, the former two reactions yielded three side products which were the results of the oxidation of the 1,3-dithiane moiety under oxidation reaction conditions. The latter resulted in the epoxide, but the poor diastereoselectivity (dr = 1 1) as well as significant loss of the PMB group were observed. 

Next, dihydroxylation of homoaUyl alcohol 2.201 was examined for the installation of the stereoselective epoxide (Scheme 2.42). The hydroxyl in 2.201 was protected as the methyl ether 2.202, which was subsequently subjected to Sharpless asymmetric dihydroxylation reaction [149] conditions to afford 2.203, however, no diastereoselectivity was observed and the reaction resulted in the oxidation of the dithiane group under such oxidation reaction conditions. 

Mukaiyama s conditions have also been used in other aerobic oxidation reactions of substrates including thiols (Table 5.2, entries 1—4, 10 and 11), alkanes (entries 8, 12 and 14) and alcohols (entries 9 and 13), as well as reactions involving lactone formation via a Baeyer-ViUiger oxidation (entries 5-7) and oxidative decarboxylation (entry 16) [15-17]. While nickel, iron and cobalt aU selectively oxidize thiols to sulfoxides, Co(II) is the most active (entries 1—4) [15 b]. Of particular synthetic interest, the chemoselective and diastereoselective aerobic oxidation of the complex sulfide, exomethylenecepham (entries 10 and 11), was observed with no overoxidation to the suUbne or oxidation of the olefin [16 a]. The diverse substrate scope in entries 1-9 suggest iron and nickel species tend to have similar reactivity with substrates, but cobalt behaves differently. For example, both iron and nickel displayed similar reactivity in Baeyer-Villiger oxidations, with cobalt being much less active (entries 5-7), yet the opposite trend was observed for sulfide oxidation (entries 1—4) [15]. Lastly, illustrating the broad potential scope of Mukaiyama-type oxidations, alcohol oxidation (entries 9 and 13) and oxidative decarbonylation (entry 15) reactions, which are oxidase systems, have also been reported [16b, 17b]. 

Scheme 3 Diastereoselective oxidation reaction of 4b with m-CPBA.

Sequential Diastereoselective Reactions of Resultant Silyl Enol Ethen. Next, our attention was focused on the sequential diai ereoselective reactions with electrophiles (Scheme 6). The oxidation reaction of the F-C product ((Z)-10b) by m-CPBA proceeded to give the 5y -diastereomer in its unprotected form in hl chemical yield and hi diastereoselectivity through die above transition state (Figure 2). These products arc of synthetic importance because of similar skeletal features to Merck L-784512 (66) with cyclooxygcnase-2 selective inhibitory activity. The protodesilylation reaction of die F-C product ((Z)-10c) by TBAF also proceeded stereoi lectively to give the a ft -diastcreomer in quantitative yield in a similar manner to that by m-CPBA oxidation. ITie diastereomeric excess of 5c was determined by HPLC analysis Daicel, CHIRALPAK AS, n-hexane i-PrOH = 95 5,0.8 ml/min, 254 nm, t = 16 min syn yj min (anti). 

One of the most significant developmental advances in the Jacobsen-Katsuki epoxidation reaction was the discovery that certain additives can have a profound and often beneficial effect on the reaction. Katsuki first discovered that iV-oxides were particularly beneficial additives. Since then it has become clear that the addition of iV-oxides such as 4-phenylpyridine-iV-oxide (4-PPNO) often increases catalyst turnovers, improves enantioselectivity, diastereoselectivity, and epoxides yields. Other additives that have been found to be especially beneficial under certain conditions are imidazole and cinchona alkaloid derived salts vide infra). 

The validity of the model was demonstrated by reacting 35 under the same reaction conditions as expected, only one diastereoisomer 41 was formed, the structure of which was confirmed by X-ray analysis. When the vinylation was carried out on the isothiazolinone 42 followed by oxidation to 40, the dimeric compound 43 was obtained, showing that the endo-anti transition state is the preferred one. To confirm the result, the vinyl derivative 42 was oxidized and the intermediate 40 trapped in situ with N-phenylmaleimide. The reaction appeared to be completely diastereoselective and a single diastereomer endo-anti 44 was obtained. In addition, calculations modelling the reactivity of the dienes indicated that the stereochemistry of the cycloaddition may be altered by variation of the reaction solvent. 

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