Sulfides diastereoselectivity

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. ... 

The highly regio- and diastereoselective addition of an alkyl and an arylthio group to an olefinic double bond ( carbosulfenylation ) is achieved with arenesulfenyl chlorides and alkyl-chloro-titanium(IV) species (Reetz reagent, from R2Zn/TiCU 5 1 M. T. Reetz, 1987, 1989), Use of the more bulky 2,4,6-triisopropylbenzenesulfenyl chloride improves the yield of the highly versatile alkyl aryl sulfide products. 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

Metzner et al. also prepared the selenium analogue 17 of their C2 symmetric chiral sulfide and tested it in epoxidation reactions (Scheme 1.6) [8]. Although good enantioselectivities were observed, and a catalytic reaction was possible without the use of iodide salts, the low diastereoselectivities obtained prevent it from being synthetically useful. 

These results indicate that the a-lithio sulfides are not configurationally stable at —78 C and thus, the high diastereoselectivity reflects the thermodynamic preference of 35 A over 35B3). 

Freparatively useful induced diastereoselectivities have been reported mainly for 1,1-di-substituted allyllithium derivatives which bear carbanion-stabilizing substituents. l-[Methyl-thio-l-(trimethylsilyl)-2-propenyl]lithium106 and the appropriate 1-phenylthio107 derivative, generated from the allylic sulfide with sec-butyllithium, in the reaction with tetrahydropyranyl-protected pregnolone, furnish a single diastereomer. 

Allylic titanates having an electrofugal leaving group, e.g., trimethylsilyl68 75 - 77, at the 3-position are powerful reagents for the highly stereoselective synthesis of 1-hetero-substituted 3-alkadienes. For the carbonyl addition of the appropriate titanated allyl sulfides ( ) or carbamates ( and ), reliable y-selectivity and anti diastereoselectivity are reported. The... 

Modena and colleagues47 have developed use of some chiral, non-racemic terpene alcohols as directing groups for highly diastereoselective m-chloroperbenzoic oxidation of sulfides into sulfoxides. Specifically the isobornyl vinylic sulfides 8 undergo hydroxyl-directed oxidation to give a 9 1 ratio of diastereomeric sulfoxides (equation 11). 

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

An example of an iron-catalyzed C-C bond formation reaction was reported in 2001 [89]. Treatment of propargyl sulfides 87 with trimethylsilyldiazomethane in the presence of 5 mol% FeCl2(dppb) gave substituted homoallenylsilanes 88 in good to moderate yields (Scheme 3.43). The silanes 88d and 88e, which bear two centers of chirality, were obtained as 1 1 mixtures of diastereomers. Slight diastereoselectivity (2 1) was seen for the formation 88f, which is an axially chiral allene with a sterogenic center. 

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

Cycloaddition of nitrones (e.g. 166, equation 107) to alkoxyaUtenes proceeds in high yield with complete diastereoselectivity, giving 1,2-isoxazolidines of type 167. Similar reactions have been reported for vinyl ethers , vinyl acetate , enamines , vinyl imidazoles , enamides, vinyl sulfones and vinyl sulfides . Since the resultant 1,2-oxazolidines of type 167 and its analogs can be hydrolyzed under acidic conditions, this reaction may also be considered as an approach to O-unsubstituted N-alkylhydroxylamines . 

Deprotonation with alkyllithium and silylation with chlorotrimethylsilane of the sulfide, 2-(l-methyl-2-phenylthioethyl)-l,3-dioxolane (1) gave the antz -diastereomer anti-2-[ R,2S)- -methyl-2-phenylthio-2-trimethylsilyl]-l,3-dioxolane (5a) with very high diastereoselectivity (d.r. 98 2)56. 

Although substrate-induced diastereoselection can be conveniently achieved when the alkenylmetal was coordinated by an oxygen atom, other heteroatoms such as sulfur and nitrogen resulted in high inductions as illustrated by the crotylzincation of the organolithium reagents derived from the allylic sulfide 238 or the tertiary amine 239 (equation 117)154. 

V(V), Mo(VI) and Ti(IV) derivatives proved to be both effective and selective in the oxidation of sulfides with alkyl hydroperoxides324. As for H2O2, vanadium is at least twofold more efficient than molybdenum in oxidation and much more selective, as proved by the data obtained with the cyclic disulfide 2-aryl-1,3-dithiolane 80. A large predominance of the tra .y-S-oxide 81 over the c/.v-dcri vati ve 82 is obtained for all the systems investigated (equation 46). However, the diastereoselectivity exhibited by V(V)/TBHP is remarkable315-325. 

A remarkably high diastereoselective excess was obtained in the addition of the anion of (S)-(-)-methyl 1-naphthyl sulfoxide to n-alkyl phenyl ketones. The sulfoxide was prepared in optically pure form by oxidation of the complex of methyl 1-naphthyl sulfide and 13-cyclodextrin with peracetic acid followed by crystallization. Desulfurization of the adducts provided enantiomerically pure tertiary alcohols (393]. 

Enantioselective oxidation of sulfides. m-Chloroperbenzoic acid attacks the sulfide 1 preferentially from the less hindered direction to introduce an oxygen atom with high diastereoselectivity.3... 

In the reactions with mono- and 1,2-disubstituted olefins, however, no ene product was obtained. This limitation has been overcome by the use of vinylic sulfides and selenides instead of mono- and 1,2-disubstituted olefins. With these substrates, the ene products are obtained with comparably high enantioselectivity and high diastereoselectivity [15]. The synthetic utility of the vinylic sulfide and selenide is shown in the synthesis of enantiopure (R)-(-)-ipsdienol, an insect-aggregation pheromone (Scheme 8C.4) [16]. 

The scope and limitations of the metal anions of 2-halo-l,3-dithiane trans-1,3-dioxide as diastereoselective carbonyl anion equivalents has been explored with regard to reaction with aldehydes.79 Reactions of metallated trans-, 3-dithiolanc 1,3-dioxide (five-membered ring) with aldehydes under kinetic and thermodynamic control have also been studied and contrasted with those of the metallated monooxide, parent sulfide, and 1,3-dithiane 1,3-dioxide (six-membered ring).80... 

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