Selenoxides enantioselectivity

Chiral sulfoxides or selenoxides.1 This oxaziridine (1) is generally more effective than the modified Sharpless reagent of Kagan (13, 52) for enantioselective oxidation of alkyl aryl sulfides or selenides to the corresponding sulfoxides or selenoxides. The polar Cl groups of 1 improve both rate and the enantioselectivity. 

Similar reactions were also achieved by the formation of diastereomeric optically active selenoxides as intermediates in the elimination reaction. Optically active ferrocenyl diselenide 19 was used in selenenylations of alkynes generating vinyl selenides of type 164. Oxidation of the selenides was performed with mCPBA under various reaction conditions which afforded the corresponding chiral selenoxides, which, after elimination, afforded axial chiral allenecarboxylic ester derivatives 165 in high enantioselectivities (R = Me 89% ee, R=Et 82% ee, R = C3H7 85% ee) (Scheme 47)>85 87... 

Other convenient reagents for the imidation of sulfides and selenides are imidoiodanes such as A-(/>-tolylsulfonyl)-imino(phenyl)iodane (PhI=NTs).304 Unfortunately, these reagents are sometimes difficult to prepare due to their thermal sensitivity and some have even been claimed to be explosive.305 Selenimides are tricoordinate tetravalent compounds and can be isolated in optically active forms. They can be prepared from optically active selenoxides, a reaction which was shown to occur with an overall retention of stereochemistry.306 They can also be obtained by optical resolution of a diastereomeric selenimide and stereochemical issues including kinetics of epimerization by pyramidal inversion were studied in detail.307 Also the enantioselective imidation of prochiral selenides of type 179 is possible by using a combination of A-(/>-tolylsulfonyl)imino(phenyl)iodane (PhI=NTs) and a catalytic amount of... 

Selenoxides derived from unsymmetrical selenides are chiral and stable toward pyramidal inversion at room or even higher temperatures. They are produced enantioselectively by the use of chiral oxidants such as the Sharpless reagent or camphor-derived oxaziridines or diastereoselectively with achiral oxidants when one of the selenide substituents is itself chiral (see Section 9). Racemic selenoxides have been resolved by chromatography over chiral adsorbents. Chiral selenoxides racemize readily in water, particularly under acid-catalyzed conditions, presumably via the intermediacy of achiral selenoxide hydrates (equation 2). 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

Until quite recently the isolation of optically active selenoxides has been limited to those contained in steroids (isolated as diastereoisomers). The difficulty in obtaining these compounds was attributed to the racemization through the achiral hydrated intermediates. Simple optically active selenoxides (5-11% ee) were first prepared by kinetic resolution. Direct oxidation of selenides to selenoxides was first reported using optically active oxaziridine derivatives under anhydrous conditions, but the extent of the asymmetric induction was somewhat unsatisfactory with methyl phenyl selenide as substrate (8-9% ee). Recently much improved enantiomeric excesses (45-73%) were achieved with new oxaziridine reagents such as (70). An attempt at the asymmetric oxidation of more bulky selenides was independently carried out using Bu OCl in the presence of (-)-2-octanol (equation 55),2 but resulted in unsatisfactory enantioselectivities (ee 1%). Much better results were obtained by the oxidation of P-oxyalkyl aryl selenides (ee 18-40% equation 56) and alkyl aryl selenides (ee 1-28%) 2S using TBHP in the presence of (+)- or (-)-diisopropyl tartarate (DIPT) and titanium(IV) alkoxide. 

Michael reaction of selenophenols. Selenophenols (and other selenides) undergo enantioselective 1,4-addition to cyclohexenone in the presence of catalytic amounts of cinchona alkaloids. Chemical yields are high optical yields are 10-43%. Usually the optical yield can be enhanced by crystallization. In one case the addition product was converted into an optically active allylic alcohol by hydride reduction followed by selenoxide fragmentation. ... 

Very recently, the enantioselective protonation of simple enolates was developed [41] using diastereoisomerically pure y-hydroxyselenoxides, derived from the 2-exo-hydroxy-lO-bornyl group, as chiral compounds. The selenoxides 84, containing various aryl groups, were prepared by treatment of the corresponding isomerically pure chloroselenuranes 85 with sodium hydrogen carbonate [41c] (Eq. 17 ... 

The results of the enantioselective protonation of some other enolates carried out under the optimal condititions with the selenoxide 84 e as the CPS are summarized in Eqs. (18) and (19). 

There are two methods for obtaining the chiral selenoxides by direct oxidation of the corresponding selenides. One is the enantioselective oxidation of pro-chiral selenides, and the other is the diastereoselective oxidation of selenides bearing a chiral moiety (Eq. 4) ... 

In the former case, almost complete stereoselective oxidation to the chiral selenoxides has been accomplished quite recently. The Davis oxidant, 3,3-di-chloro-l,7,7-trimethyl-2 -(phenylsulfonyl)spirobicyclol2.2.11heptane-2,3 -oxa-ziridine, was found to be the most efficient reagent for the enantioselective oxidation of a variety of prochiral alkyl aryl selenides [81. Asymmetric oxidation was accomplished by the treatment of the selenides with 1 molar equivalent of the Davis oxidant at 0°C to afford the corresponding chiral alkyl aryl selenoxides in quantitative yields with 91-95% ee (Scheme 1). The oxidation of methyl phenyl selenide was complete within 1 min, whereas that of triiso-propyl(a bulkier alkyl) phenyl selenide required a few hours. Typical results are... 

Scheme 2. Enantioselective oxidation of the alkyl aryl selenides to the selenoxides using the Sharpless oxidant...

Enantioselective Selenoxide Elimination Producing Optically Active Allenes and or,]3-Unsaturated Ketones... 

Thus, when cyclohexyl selenides 1, prepared from the corresponding 4-sub-stituted cyclohexanone via the selenoketals, were oxidized with various Davis and Sharpless oxidants, the chiral alkyl aryl 4-substituted cyclohexylidenemethyl ketones were obtained in excellent chemical yields with high enantiomeric excesses. Typical results are summarized in Table 4. In this asymmetric induction, of the substrate and the chiral oxidant employed were revealed to show a remarkable effect upon the enantioselectivity of the product. The use of a methyl moiety as instead of a phenyl moiety gave a higher ee value, probably due to the steric difference between the two groups bonded to the selenium atom of the substrate. The results indicate that the titanium complex of the Sharpless oxidant may promote the racemization of the chiral selenoxide intermediate by acting as a Lewis acid catalyst, whereas the racemization in the case of the Davis oxidant, which is aprotic in nature, is slow. 

The oxidation of the chiral ferrocenyl vinyl selenides, prepared from the optically active diferrocenyl diselenides and ethyl propiolate derivatives, with 1 molar equivalent of MCPBA under various conditions afforded the corresponding chiral selenoxides. The chiral selenoxides suffered in situ selenoxide elimination to afford the axially chiral allenecarboxyUc esters in moderate chemical yields with high enantioselectivities (Scheme 10). Typical results are shown in Table 5. The reaction temperature had a remarkable effect upon stereoselectivity and the lower temperature gave better results. The addition of molecular sieves (4 A) to the reaction system improved the stereoselectivity. Dichlo-romethane was revealed to be the solvent of choice. In other words, reaction conditions to suppress the racemization of a diastereomeric selenoxide intermediate were required. Asymmetric selenoxide elimination provides a new method for the preparation of the chiral allenecarboxyUc esters which have so far been prepared by optical resolution of the corresponding racemic acids. 

If the chiral allylic selenoxides were obtained by enantioselective or diaste-reoselective oxidation of the allylic selenides, the formation of the corresponding chiral allylic alcohols is expected after the hydrolysis of the intermediate chiral allylic selenenates obtained by chirality transfer in the rearrangement... 

In a previous section, the asymmetric [2,3]sigmatropic rearrangement of chiral selenoxides, prepared by diastereoselective oxidation or enantioselective... 

Several oxaziridines related to (14) (eq 8) have been used, most notably in the enantioselective oxidation of sulfides to sulfoxides, of selenides to selenoxides, and of alkenes to oxiranes, It is also the reagent of choice for the hydroxylation of lithium and Grignard reagents and for the asymmetric oxidation of enolates to give a-hydroxy carbonyl compounds, - A similar chiral fluorinating reagent has also been developed, ... 

Enantioselective oxidation of Z-aryl cinnamyl allylic selenide (83) with oxaziridine (—)-(69) gave 1-phenyl allyl alcohol (85) via an allyl selenoxide-selenate [2,3] sigmatropic rearrangement (Scheme... 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

Related reagents 2.83, obtained from camphor imine, are usefid for asymmetric oxidation of sulfides and selenides to chiral sulfoxides and selenoxides [S06, 749]. To obtain high enantioselectivities, the substituents on the sulfur or selenium must be of a sufficiently different size. 

Camphor-derived, V- s u 1 fo n y 1 ox azi ri d in es 51-58 are chiral oxidants which are able to oxidize a variety of substrates enantioselectively. They have been used for the epoxidation of alkenes (Section D.4.5.2.I.), the preparation of chiral sulfoxides and selenoxides (Section D.4.11.2.1.), and enantioselective hydroxylation of enolates (Section D.4.I.). 

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