Diastereoselective oxidations

The common denominator for all the previous approaches to the perylenequinones is a diastereoselective oxidative coupling of homochiral 2-naphthols. Our group proposed an alternative enantioselective convergent synthesis that would greatly... 

Enantioselective a-hydroxylotion of carbonyl compounds. The lithium enolates of the SAMP-hydrazones of ketones undergo facile and diastereoselective oxidation with 2-phenylsulfonyl-3-phenyloxaziridine (13, 23-24) to provide, after ozonolysis, (R)-a-hydroxy ketones in about 95% ee. High enantioselectivity in hydroxylation of aldehydes requires a more demanding side chain on the pyrrolidine ring such as —QCjHOjOCH, which also results in reversal of the configuration. 

Up to date, the scientists involved in these investigations used only few commercial catalysts, predominantly Pd/C, Pt/C, Pt02, or Raney nickel. But except for a few cases, these catalysts are not selective enough and only a mixture of diastereomers results from the reactions. The separation of the pure diastereomers is expensive and requires a lot of energy and reagents. Even more complicate is the case of diastereoselective oxidation. 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

Figure 6.4 Effect of pressure on the diastereoselective oxidation of a protected methyl cysteine. Reproduced by Permission of the Royal Society of Chemistry...

Alkyl-substituted olefins are also epoxidized by CPO. The oxidation of functionalized terminal olefins by CPO catalysis with fBuOOH as oxygen donor affords the corresponding epoxides in good ee values (entries 20, 22, 24-26). While cz5-substituted olefins were epoxidized by CPO with H2O2 in good to excellent enantiomeric excesses (entries 32-35), the trans compounds were poorly converted. The enantioselective CPO-catalyzed epoxidation has been intensively investigated, although examples of diastereoselective oxidations (entries 43-45) are rare. 

When a prochiral sulfide is submitted to the oxidation by DMD or TFD, the corresponding racemic sulfoxide is produced, whereas in the case of a chiral sulfide, diastereoselective oxidation is feasible. For example, a good diastereoselectivity was obtained with the chiral cyclic disulfide in equation 21. ... 

VO(acac)2/TBHP CATALYZED EPOXIDATION OF 2-(2-ALKENYL)PHENOLS. HIGHLY REGIO- AND DIASTEREOSELECTIVE OXIDATIVE CYCLIZATION TO 2,3-DIHYDROBENZOFURANOLS AND 3-CHROMANOLS... 

Diastereoselective Oxidation of P-Methylstyrene by Wild-Type, L29H/H64L, and F43H/H64L Mb... 

Scheme 1.12. Diastereoselective oxidation of 4-tert-butyl-l-methyl piperidine [32, 36, 37],...

An asymmetric synthesis of benzenesulfinates bearing a phosphonate group at the ortho -position has been achieved by a diastereoselective oxidation of the correspond- (g) ing sulfenates with chiral oxaziridines.210... 

A nickel catalyst containing Me-DuPhos has been shown to be effective in the enantioselective isomerization of 4,7-dihydro-l,3-dioxepins 72.71 Diastereoselective oxidation of the resulting 4,5-dihydro-l,3-dioxepins 73 allowed access to a range of C-4 chiral synthons (Scheme 13.26). 

Achiral primary allylic alcohols undergo enantioselective epoxidation (cf. Figure 3.35), whereas—chiral primary allylic alcohols undergo diastereoselective oxidation. So the reagent... 

Most reports on diastereoselective oxidation of sulfides are substrate-directed. Diastereoselectivity has been achieved by either steric- or neighboring-group participation.21 Incipient hydrogen bonding between the substrate hydroxyl group and the incoming percarboxylic acid has been evoked to explain the high diastereoselectivity observed in the oxidation of 10-exo-hydroxy-bornyl- derivatives 7 and 9 (Scheme 1). The oxidation of 9 with m-CPBA in MeOH occurs without stereoselectivity. 

Chloroperbenzoic acid (MCPBA) has been frequently applied to sulfide oxidation (Figure 3.96). MCPBA has been the oxidant of choice for the diastereoselective oxidation of 2-exo-hydroxynorbornyl systems containing a sulfide group in the 10 position and a diastereomeric excess (d.e.) of 80-90% is obtained. However, if the hydroxide function is protected as the ether, the d.e. drops to 30%.387 388... 

Sulfoxides can also be transformed to sulfones using catalysed hydrogen peroxide systems. The catalysts can be molybdenum,403 zirconium,404 vanadium405 and selenic406 salts. The use of Mo02(acac)2 with /-butyl hydroperoxide (TBHP) as a diastereoselective oxidation system has been reported, but yields and selectivity are at best moderate (Figure 3.99). 

Figure 3.99 Diastereoselective oxidation of sulfides using a Mo02(acac) JTBHP system.

Iron porphyrin catalysts with TBHP have been used for the diastereoselective oxidation of sulfides affording up to 46% d.e.408 A series of manganese(salen) catalysts with hydrogen peroxide has been employed for the oxidation of aralkyl sulfides in 34-70% d.e. and 80-90% yield. The best catalyst was derived from enantiomerically pure trans-1,2-diaminocyclohexane (Figure 3.101).409... 

Figure 3.100 Diastereoselective oxidation of sulfides to sulfoxides using a VO(acac)2l TBHP system.

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